CN120787219A - Compound with substituted glutarimido isoindolinone novel skeleton and application thereof - Google Patents

Abstract

To a compound of formula (I), a compound of formula (I') or a salt, enantiomer, stereoisomer, solvate, polymorph thereof and uses thereof. Also disclosed are pharmaceutical compositions comprising, as active ingredient, a compound of formula (I), or a salt, enantiomer, stereoisomer, solvate, polymorph thereof, and uses thereof. A series of compounds designed to be synthesized are effective in preventing or treating diseases or disorders associated with the cereblon protein.

Description

Compound with substituted glutarimido isoindolinone novel skeleton and application thereof Technical Field

The present disclosure relates to compounds of formula (I), formula (I') or salts, enantiomers, stereoisomers, solvates or polymorphs thereof, and uses thereof, particularly for the prevention or treatment of diseases or conditions associated with the cereblon protein.

Background

Thalidomide, lenalidomide and other phthalimide immune regulation drugs (IMiDs) have remarkable curative effects on treating hematological tumors and autoimmune diseases, but until 2010, direct binding proteins of the drugs are identified as E3 ubiquitin ligase Cereblon (CRBN), and after the drugs are combined with CRBN, the drugs can be used as molecular glue to recruit substrate proteins (such as transcription factors IKZF1/3 and the like), so that protein interaction occurs between the CRBN and the substrate proteins to ubiquitinate the substrate proteins, and the substrate proteins after polyubiquitination are identified and degraded by proteasome, so that pharmacological effects including anti-tumor, immune regulation and the like are generated. The molecular mucin degradation agent directly targets and degrades and eliminates target proteins, and has the potential advantages of targeting target targets which are not patent medicine. And the molecular gel degradation agent has small molecular weight and good pharmaceutical property, so the research and development of the medicine are very challenging. Based on CRBN E3 ubiquitin ligase and molecular gel degradation mechanism, a series of compounds have been developed, such as pomalidomide on the market and the BASED MEASUREMENT (BMS) company CC-122, CC-220, CC-90009, CC-99282 and CC-92480, BMS-986470, the Novartis company DKY709, and the CFT7455 of C4 Therapeutics, the MRT-6160 of Monte Rosa, etc. in clinical trials. The degradation substrates of the molecular adhesives are also expanded from the originally discovered transcription factors IKZF1/3 to casein kinase 1 alpha (CK 1 alpha), zinc finger protein 91 (ZFP 91), WIZ, transcription factors IKZF2, translation factors GSPT1, immune disease targets Vav1 and the like, and the degradation of the protein substrates can lead the molecular adhesives to exert the drug effect activities of immune regulation, anti-inflammatory, anti-tumor and the like. The molecular gel candidate compound designed and developed at present has very limited structural novelty, so the molecular gel compound with novel framework and diversified framework is designed and developed to become a research hot spot in the field.

Thus, there is an urgent need for a novel array of CRBN E3 ubiquitin ligase ligand backbones and their application in the development of potent molecular gel degrading agents for the treatment and/or prevention of degraded protein mediated or associated diseases or conditions.

Disclosure of Invention

In view of the above, it is an object of the present disclosure to provide proteolytic compounds having a novel framework of substituted glutarimido isoindolinone, methods of their preparation, uses, and methods of their use.

To achieve the above and other related objects, in one aspect, the present disclosure provides a compound of formula (I) or a salt, stereoisomer (including enantiomer, diastereomer), isotopically enriched analog, solvate or polymorph thereof: Wherein Z represents C (O), CH ₂ or CD ₂;R_a1、R_a2、R_a3 and R _a4 each independently represent hydrogen, deuterium, halogen, C _1-6 alkyl, Halogenated C _1-6 alkyl, deuterated C _1-6 alkyl, C _1-6 alkoxy, Deuterated C _1-6 alkoxy or halogenated C _1-6 alkoxy (R _a5)_m represents an isoindoline ring which is connected with the deuterated C _1-6 alkoxy or halogenated C _1-6 alkoxy, which is optionally substituted by m R _a5, each R _a5 is the same or different and each independently represents deuterium, Halogen, hydroxy, mercapto, nitro, amino, cyano, C _1-6 alkyl, halo C _1-6 alkyl, deuterated C _1-6 alkyl, C _1-6 alkoxy, Deuterated C _1-6 alkoxy, halogenated C _1-6 alkoxy, C _2-6 alkenyl or C _2-6 alkynyl, m represents an integer of 0, 1.2 or 3;R: Wherein ring A ₁ represents a heterocyclylene group containing at least 2 nitrogen atoms, (Rd ₁)_n1 represents that ring A ₁ is optionally substituted with n 1R _d groups, each R _d independently represents deuterium, Halogen, hydroxy, mercapto, nitro, amino, cyano, oxo, C _1-6 alkyl, deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, Halogenated C _1-6 alkoxy or C _1-6 alkoxy, and N1 represents an integer from 0 to 20, and R ₁ represents N (R _w), wherein R _w represents hydrogen or C _1-3 alkyl, and R ₂ represents a bond, or R ₂ represents CH ₂ or C (O), or R ₁ represents a bond, and R ₂ represents N (R _w), wherein R _w represents hydrogen or C _1-3 alkyl, or R ₂ represents N (R _w) C (O), wherein R _w represents hydrogen or C _1-3 alkyl, or R ₂ represents-N=CH-, or R represents: Wherein R _X represents NH, -n=ch-, or N (R _w) C (O), wherein R _w represents hydrogen or C _1-3 alkyl, or R represents: Wherein ring A ₂ represents a heterocyclylene group containing 1 nitrogen atom, (R _d4)_n4 represents ring A ₂ optionally substituted with n 4R _d4 groups, each R _d4 independently represents deuterium, halogen, hydroxy, mercapto, nitro, amino, cyano, oxo, C _1-6 alkyl, deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, halogenated C _1-6 alkoxy or C _1-6 alkoxy, and n4 represents an integer of 0 to 20, and wherein R _y1 represents The symbols indicate the point of attachment to ring A ₂, and R ₂ represents N (R _w) C (O), wherein R _w represents hydrogen or C _1-3 alkyl, the symbols in the above formulae indicate the point of attachment to R _c, and R _c represents CR _c1R_c2, wherein R _c1 and R _c2 each independently represent H, Deuterium, halogen, optionally substituted straight-chain or branched alkyl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aryl or optionally substituted heteroaryl, or R _c represents a bond, ring B represents cycloalkylene, heterocyclylene, arylene or heteroarylene, m1 represents an integer of 0 or 1, (R _d2)_n2 represents ring B optionally substituted by n 2R _d2 groups, each R _d2 independently represents deuterium, c _1-6 alkyl, deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, C _1-6 alkoxy, halogenated C _1-6 alkoxy, Halogen, amino, hydroxy, mercapto, cyano, oxo, C _2-6 alkynyl or C _2-6 alkenyl, and n2 represents an integer from 0 to 20, and ring C represents heterocyclyl, cycloalkyl, aryl or heteroaryl, (R _d3)_n3 represents ring C optionally substituted by n 3R _d3 groups, each R _d3 independently of the others represents deuterium, c _1-6 alkyl, deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, C _1-6 alkoxy, halogenated C _1-6 alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C _2-6 alkynyl or C _2-6 alkenyl, and n3 represents an integer of 0 to 20, with the proviso that 3- (5- ((4-benzhydryl piperazin-1-yl) amino) -1-oxoisoindolin-2-yl) piperidine-2, 6-dione, 3- (5- ((4- ((4 '-chloro- [1,1' -biphenyl ] -2-yl) methyl) piperazin-1-yl) amino) -1-oxoisoindolin-2-yl) piperidine-2, 6-dione, 3- (5- ((4 '-chloro-5, 5-dimethyl-3, 4,5, 6-tetrahydro- [1,1' -biphenyl ] -2-yl) methyl) piperazin-1-yl) amino) -1-oxoisoindolin-2, 6-dione, and 3- (5- ((4- (4 '-chloro-5, 5-dimethyl-3, 4,5, 6-tetrahydro- [1,1' -biphenyl ] -2-carbonyl) piperazin-1-yl) amino) -1-oxoisoindolin-2-yl) piperidine-2, 6-dione are excluded.

In another aspect, the present disclosure provides a compound of formula (I'), or a salt, stereoisomer (including enantiomer, diastereomer), isotopically enriched analog, solvate, or polymorph thereof: Wherein Z represents C (O), CH ₂ or CD ₂;R_a1、R_a2、R_a3 and R _a4 each independently represent hydrogen, deuterium, halogen, C _1-6 alkyl, Halogenated C _1-6 alkyl, deuterated C _1-6 alkyl, C _1-6 alkoxy, Deuterated C _1-6 alkoxy or halogenated C _1-6 alkoxy (R _a5)_m represents an isoindoline ring which is connected with the deuterated C _1-6 alkoxy or halogenated C _1-6 alkoxy, which is optionally substituted by m R _a5, each R _a5 is the same or different and each independently represents deuterium, Halogen, hydroxy, mercapto, nitro, amino, cyano, C _1-6 alkyl, halo C _1-6 alkyl, deuterated C _1-6 alkyl, C _1-6 alkoxy, Deuterated C _1-6 alkoxy, halogenated C _1-6 alkoxy, C _2-6 alkenyl, C _2-6 alkynyl or heterocyclyl, optionally via one or more groups independently selected from halogen, C _1-6 alkyl and tert-butoxycarbonyl, m represents an integer of 0, 1, 2 or 3, ring A ₁ represents a 4-to 30-membered heterocyclic group containing at least 2 nitrogen atoms, (R _d1)_n1 represents that ring A ₁ is optionally substituted by n 1R _d1 groups, each R _d1 independently represents deuterium, Halogen, hydroxy, mercapto, nitro, amino, cyano, oxo, C _1-6 alkyl, deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, Halo C _1-6 alkoxy or C _1-6 alkoxy, and N1 represents an integer from 0 to 20, and R ₁ represents N (R _w) wherein R _w represents hydrogen or C _1-3 alkyl optionally substituted with one or more substituents independently selected from optionally substituted aryl and optionally substituted heteroaryl, and R ₂ represents a bond, or R ₁ represents a bond, and R ₂ represents N (R _w) wherein R _w represents hydrogen or C _1-3 alkyl, and R _e represents a bond, or R _e represents C (O) O, or R _e represents a structure of the formula: R _e1 represents C (O), CH ₂ or haloCH ₂, ring D represents arylene, (R _e2)_m2 represents that ring D is optionally substituted by m 2R _e2 groups, each R _e2 independently represents deuterium, c _1-6 alkyl, deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, C _1-6 alkoxy, halogenated C _1-6 alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C _2-6 alkynyl or C _2-6 alkenyl, and m2 represents an integer of 0 to 20, and ring E represents a nitrogen-containing heterocyclylene group, m4 represents an integer of 0 or 1, (R _e3)_m3 represents a ring E optionally substituted with m 3R _e3 groups, each R _e3 independently represents deuterium, c _1-6 alkyl, deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, C _1-6 alkoxy, halogenated C _1-6 alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C _2-6 alkynyl or C _2-6 alkenyl, and m3 represents an integer of 0 to 20; the symbol # indicates the point of attachment to R _f, and R _f represents a C _1-10 alkyl group, said C _1-10 alkyl group optionally substituted with one or more substituents independently selected from the group consisting of halogen, Optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted cycloalkyl and NR ₃R₄, wherein R ₃ and R ₄ each independently represent H, C _1-3 alkyl or optionally substituted cycloalkyl, with the proviso that 3- (5- ((4-benzhydryl piperazin-1-yl) amino) -1-oxoisoindolin-2-yl) piperidine-2, 6-dione, 3- (5- ((4- ((4 '-chloro- [1,1' -biphenyl ] -2-yl) methyl) piperazin-1-yl) amino) -1-oxoisoindolin-2-yl) piperidine-2, 6-dione, and 3- (5- ((4- ((4 '-chloro-5, 5-dimethyl-3, 4, 6-tetrahydro- [1,1' -biphenyl ] -2-yl) methyl) piperazin-1-yl) amino) -1-oxoisoindolin-2, 6-dione are excluded.

In another aspect, the present disclosure provides a pharmaceutical composition comprising the compound of formula (I) or a pharmaceutically acceptable salt, stereoisomer (including enantiomer, diastereomer), solvate, isotopically enriched analog or polymorph thereof, and at least one pharmaceutically acceptable carrier, or the compound of formula (I') or a pharmaceutically acceptable salt, stereoisomer (including enantiomer, diastereomer), solvate, isotopically enriched analog or polymorph thereof, and at least one pharmaceutically acceptable carrier.

In another aspect, the present disclosure also provides a kit or kit comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof or a pharmaceutical composition comprising the same, or a compound of formula (I') or a pharmaceutically acceptable salt thereof or a pharmaceutical composition comprising the same.

In another aspect, the present disclosure provides the compound of formula (I) or formula (I') or a pharmaceutically acceptable salt, enantiomer, diastereomer, solvate or polymorph thereof, for use as a medicament.

In another aspect, the present disclosure provides a compound of formula (I) or formula (I'), or a pharmaceutically acceptable salt, stereoisomer (including enantiomer, diastereomer), solvate, isotopically enriched analog or polymorph thereof, or a pharmaceutical composition of the disclosure, for use in treating or preventing a disease or disorder associated with a cereblon protein.

In another aspect, the present disclosure also provides the use of a compound of formula (I) or formula (I') or a pharmaceutically acceptable salt, stereoisomer (including enantiomer, diastereomer), solvate, isotopically enriched analog or polymorph thereof, or the pharmaceutical composition of the disclosure, for the preparation of a medicament for treating or preventing a disease or disorder associated with a cereblon protein.

In another aspect, the present disclosure also provides a method of treating or preventing a disease or disorder associated with cereblon protein in a subject, comprising administering to the subject a therapeutically effective amount of the compound of formula (I) or compound of formula (I'), or a pharmaceutically acceptable salt, stereoisomer (including enantiomer, diastereomer), solvate, isotopically enriched analog, or polymorph thereof, or the pharmaceutical composition.

In another aspect, the present disclosure also provides a process for preparing a compound of formula (I), comprising using a compound of formula (M1) and a compound of formula (M2) as starting materials to prepare a compound of formula (I): Wherein R _a1、R_a2、R_a3、R_a4、(R_a5)_m, Z, R, ring B, ring C, (R _d2)_n2、(R_d3)_n3), and m1 are as defined in the disclosure of compounds of formula (I) and sub-embodiments thereof, and R _w3 represents CHO, COOH or Wherein R _c2 is as defined in the compounds of formula (I) and sub-embodiments thereof, and the group LE represents Cl, br, I, OM _s、OT_s, or ON _s, wherein (1) -R _w1-R_w2 representAnd R representsOr (2) -R _w1-R_w2 representsAnd R representsOr (3) -R _w1-R_w2 represents-NH-NH ₂ and R represents-NH-, or (4) -R _w1-R_w2 representsAnd R representsWherein R _w, ring A ₁、(R_d1)_n1, ring A ₂ and R _d4)_n4 are as defined in the compounds of formula (I) of the present disclosure and in their sub-embodiments, wherein R _c3 and R _c4 represent H when R _w3 represents CHO, or R _c3 and R _c4 together form a carbonyl group when R _w3 represents COOH, or R _w3 representsWhen R _c3 represents H, and R _c4 is R _c2. Detailed Description

The following detailed description is provided as an exemplary embodiment to assist those of ordinary skill in the art in understanding and practicing the present disclosure. It will be appreciated, however, that such description is not intended to limit the scope of the present disclosure, and that various modifications and changes may be made to the particular embodiments described in the present disclosure without departing from the spirit and scope of the present disclosure, which changes and modifications fall within the scope of the present disclosure as claimed. I. Compounds of formula (I)

The present disclosure provides a compound of formula (I) or a salt (including pharmaceutically acceptable salts), stereoisomer (including enantiomers, diastereomers), solvate, isotopically enriched analog, or polymorph thereof: Wherein Z, R _a1、R_a2、R_a3、R_a4、(R_a5)_m、R、R_c, ring B, (R _d2)_n2), ring C, (R _d3)_n3 and m1 are as defined above for the compound of formula (I) and embodiments thereof.

The compound of formula (I) or a salt (including pharmaceutically acceptable salts), stereoisomer (including enantiomer), solvate, isotopically enriched analogue or polymorph thereof provided by the present disclosure has binding force to CRBN, helps recruit substrate protein, and can bind CRBN E3 ubiquitin ligase as molecular cement. The compounds of formula (I) of the present disclosure, or salts (including pharmaceutically acceptable salts), stereoisomers (including enantiomers), solvates, isotopically enriched analogs, or polymorphs thereof, may also degrade substrate proteins (e.g., IKZF1/2/3/4 proteins, WEE1 proteins, CK1 alpha proteins, GSPT1 proteins, ZFP91 proteins, etc.). The compounds of formula (I) or salts (including pharmaceutically acceptable salts), stereoisomers (including enantiomers), solvates, isotopically enriched analogs, or polymorphs thereof of the present disclosure are therefore useful in the prevention or treatment of a disease or condition associated with the cereblon protein (e.g., a tumor or cancer), or have excellent pharmacokinetic properties and are useful as therapeutic agents in tumor patients.

In some embodiments of the disclosure, R _a1、R_a2、R_a3 and R _a4 are the same or different and each independently represent H, deuterium (i.e., D), halogen (e.g., fluoro, chloro, bromo, or iodo), C _1-6 alkyl (e.g., C _1-3 alkyl, such as methyl, ethyl, or propyl), halogenated C _1-6 alkyl (e.g., halogenated C _1-4 alkyl, such as trifluoromethyl), deuterated C _1-6 alkyl, C _1-6 alkoxy (e.g., C _1-4 alkoxy, such as methoxy), deuterated C _1-6 alkoxy, or halogenated C _1-6 alkoxy (e.g., halogenated C _1-4 alkoxy, such as trifluoromethoxy). In some sub-embodiments of the present disclosure, R _a1、R_a2、R_a3 and R _a4 each independently represent H.

In some embodiments of the disclosure, Z represents C (O), CH ₂, or CD ₂.

In some embodiments of the disclosure, Z represents C (O).

In some embodiments of the disclosure, Z represents CH ₂.

In some embodiments of the disclosure, Z represents CD ₂.

In some embodiments of the disclosure, (R _a5)_m represents an isoindoline ring of formula (I) to which it is attached optionally substituted with m R _a5, each R _a5 being the same or different and each independently representing deuterium, halogen (e.g., fluorine, chlorine, bromine or iodine), a, Hydroxy, mercapto, nitro, amino, cyano, C _1-6 alkyl (e.g. C _1-5 alkyl, C _1-4 alkyl or C _1-3 alkyl, e.g. methyl), Ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C _1-6 alkyl (e.g. halogenated C _1-4 alkyl, e.g. F₃C-、FCH₂-、F₂CH-、ClCH₂-、Cl₂CH-、CF₃CF₂-、CF₃CHF-、CHF₂CF₂-、CHF₂CHF-、CF₃CH₂- or CH ₂ClCH₂ -) Deuterated C _1-6 alkyl (e.g., perdeuterated C _1-6 alkyl, perdeuterated C _1-5 alkyl, or perdeuterated C _1-4 alkyl, such as CD ₃、CD₃CD₂-、CD₃CD₂CD₂ -, etc.) C _1-6 alkoxy (e.g., C _1-4 alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), deuterated C _1-6 alkoxy, Halogenated C _1-6 alkoxy (e.g., halogenated C _1-4 alkoxy, such as F₃C-O-、FCH₂-O-、F₂CH-O-、ClCH₂-O-、Cl₂CH-O-、CF₃CF₂-O-、CF₃CHF-O-、CHF₂CF₂-O-、CHF₂CHF-O-、CF₃CH₂-O- or CH ₂ClCH₂-O-)、C_2-6 alkenyl (e.g., vinyl) or C _2-6 alkynyl (e.g., ethynyl)), and m represents an integer of 0, 1.2 or 3. In some sub-embodiments of the present disclosure, m represents an integer of 0,1, or 2. In some sub-embodiments of the present disclosure, each R _a5 is the same or different and each independently represents deuterium, halogen (e.g., fluorine, chlorine, bromine or iodine), hydroxy, mercapto, nitro, amino, cyano, C _1-4 alkyl (e.g., C _1-3 alkyl, e.g., methyl), Ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), Halogenated C _1-4 alkyl (e.g., halogenated C _1-3 alkyl, such as F₃C-、FCH₂-、F₂CH-、ClCH₂-、Cl₂CH-、CF₃CF₂-、CF₃CHF-、CHF₂CF₂-、CHF₂CHF-、CF₃CH₂- or CH ₂ClCH₂-)、C_1-4 alkoxy (e.g., C _1-3 alkoxy, such as methoxy), ethoxy, propoxy, isopropoxy, butoxy, Sec-butyloxy or tert-butyloxy) or a halogenated C _1-4 alkoxy (e.g. a halogenated C _1-3 alkoxy, such as F₃C-O-、FCH₂-O-、F₂CH-O-、ClCH₂-O-、Cl₂CH-O-、CF₃CF₂-O-、CF₃CHF-O-、CHF₂CF₂-O-、CHF₂CHF-O-、CF₃CH₂-O- or CH ₂ClCH₂ -O-).

In embodiments of the present disclosure, the number of substituents is in principle not limited by any restrictions or is automatically limited by the size of the building block.

In some embodiments of the disclosure, R representsWherein ring A ₁ represents a heterocyclylene group containing at least 2 nitrogen atoms, (R _d1)_n1 represents that ring A ₁ is optionally substituted with n1 Rd ₁ groups, each R _d1 independently represents deuterium, Halogen, hydroxy, mercapto, nitro, amino, cyano, oxo, C _1-6 alkyl, deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, Halogenated C _1-6 alkoxy or C _1-6 alkoxy, and N1 represents an integer from 0 to 20, and R ₁ represents N (R _w), wherein R _w represents hydrogen or C _1-3 alkyl, and R ₂ represents a bond, or R ₂ represents CH ₂ or C (O), or R ₁ represents a bond, and R ₂ represents N (R _w), wherein R _w represents hydrogen or C _1-3 alkyl, or R ₂ represents N (R _w) C (O), wherein R _w represents hydrogen or C _1-3 alkyl, or R ₂ represents-N=CH-, and the symbol indicates the point of attachment to R _c.

In some embodiments of the disclosure, R ₁ represents N (R _w), wherein R _w represents hydrogen or C _1-3 alkyl, and R ₂ represents a bond.

In some embodiments of the disclosure, R ₁ represents N (R _w), wherein R _w represents hydrogen or C _1-3 alkyl, and R ₂ represents CH ₂ or C (O).

In some embodiments of the disclosure, R ₁ represents a bond, and R ₂ represents N (R _w), wherein R _w represents hydrogen or C _1-3 alkyl.

In some embodiments of the disclosure, R ₁ represents a bond, and R ₂ represents N (R _w) C (O), wherein R _w represents hydrogen or C _1-3 alkyl. The symbol indicates the point of attachment to R _c.

In some embodiments of the disclosure, R ₁ represents a bond, and R ₂ represents-n=ch-. The symbol indicates the point of attachment to R _c.

In some embodiments of the disclosure, R ₁ represents N (R _w), wherein R _w represents hydrogen or C _1-3 alkyl, and R ₂ represents CH ₂ or C (O).

In some embodiments of the disclosure, R representsWherein R _X represents NH, -n=ch-, or N (R _w) C (O), wherein R _w represents hydrogen or C _1-3 alkyl, and the symbol indicates the point of attachment to R _c.

In some embodiments of the disclosure, R representsWherein ring A ₂ represents a heterocyclylene group containing 1 nitrogen atom, (R _d4)_n4 represents ring A ₂ optionally substituted with n 4R _d4 groups, each R _d4 independently represents deuterium, halogen, hydroxy, mercapto, nitro, amino, cyano, oxo, C _1-6 alkyl, deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, halogenated C _1-6 alkoxy or C _1-6 alkoxy, and n4 represents an integer of 0 to 20, and wherein R _y1 representsThe symbol indicates the point of attachment to ring a ₂, and R _y2 represents N (R _w) or N (R _w) C (O), wherein R _w represents hydrogen or C _1-3 alkyl, and the symbol indicates the point of attachment to R _c.

In some embodiments of the disclosure, R _y1 represents S, and R _y2 represents N (R _w) or N (R _w) C (O), wherein R _w represents hydrogen or C _1-3 alkyl. The symbol indicates the point of attachment to R _c.

In some embodiments of the disclosure, R _y1 represents-S-CH ₂ -, and R _y2 represents N (R _w) or N (R _w) C (O), wherein R _w represents hydrogen or C _1-3 alkyl. The symbol indicates the point of attachment to R _c.

In some embodiments of the disclosure, R _y1 represents-S-CH ₂-CH₂ -, and R _y2 represents N (R _w) or N (R _w) C (O), wherein R _w represents hydrogen or C _1-3 alkyl. The symbol indicates the point of attachment to R _c.

In some embodiments of the disclosure, R represents one of the following formulas: Wherein each R _w independently represents hydrogen or C _1-3 alkyl, and each ring A ₁ independently represents a heterocyclylene group containing at least 2 nitrogen atoms (including 4 to 30 membered heterocyclylene groups, 4 to 20 membered heterocyclylene and 4 to 15 membered heterocyclylene), (R _d1)_n1 represents ring a ₁ optionally substituted with n 1R _d1 groups, each R _d1 independently represents deuterium, Halogen, hydroxy, mercapto, nitro, amino, cyano, oxo, C _1-6 alkyl, deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, halogenated C _1-6 alkoxy or C _1-6 alkoxy, and n1 represents an integer of 0-20 (e.g., an integer of 0-10), ring A ₂ represents a heterocyclylene group containing 1 nitrogen atom (including 4-30 membered heterocyclylene groups, 4 to 20 membered heterocyclylene and 4 to 15 membered heterocyclylene), (R _d4)_n4 represents ring a ₂ optionally substituted with n 4R _d4 groups, each R _d4 independently represents deuterium, Halogen, hydroxy, mercapto, nitro, amino, cyano, oxo, C _1-6 alkyl, deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, halogenated C _1-6 alkoxy or C _1-6 alkoxy, and n4 represents an integer from 0 to 20 (e.g., an integer from 0 to 10), and the symbols indicate the point of attachment to R _c.

In some embodiments of the present disclosure, each ring a ₁ herein independently represents a heterocyclylene group containing at least 2 nitrogen atoms, for example a 4 to 30 membered heterocyclylene group, a 4 to 20 membered heterocyclylene group, or a 4 to 15 membered heterocyclylene group. Ring A ₁ is optionally substituted with n 1R _d1 groups, each R _d1 is independently deuterium, halogen, hydroxy, mercapto, nitro, amino, cyano, oxo, C _1-6 alkyl, deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, halogenated C _1-6 alkoxy or C _1-6 alkoxy, and n1 represents an integer of 0 to 20 (e.g., an integer of 0 to 10).

In some embodiments of the present disclosure, each ring a ₁ represents, independently of one another, a 4-to 30-membered heterocyclylene group containing at least 2 nitrogen atoms (including 4-to 25-membered heterocyclylene groups, 4-to 20-membered heterocyclylene groups, 4-to 15-membered heterocyclylene groups, and 5-to 20-membered heterocyclylene groups). Ring A ₁ is optionally substituted with n 1R _d1 groups, each R _d1 being independently deuterium, halogen (e.g., fluorine, chlorine, bromine or iodine), hydroxy, mercapto, nitro, amino, cyano, oxo, C _1-6 alkyl (e.g., C _1-5 alkyl), C _1-4 alkyl or C _1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C _1-6 alkyl (for example perdeuterated C _1-6 alkyl, Perdeuterated C _1-5 alkyl or perdeuterated C _1-4 alkyl, e.g., CD ₃、CD₃CD₂-、CD₃CD₂CD₂ -, etc.), Halogenated C _1-6 alkyl (e.g., halogenated C _1-4 alkyl, such as F₃C-、FCH₂-、F₂CH-、ClCH₂-、Cl₂CH-、CF₃CF₂-、CF₃CHF-、CHF₂CF₂-、CHF₂CHF-、CF₃CH₂- or CH ₂ClCH₂-)、C_1-6 alkoxy (e.g., C _1-4 alkoxy, such as methoxy), Ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), Or a halogenated C _1-6 alkoxy group (e.g., a halogenated C _1-4 alkoxy group, such as F₃C-O-、FCH₂-O-、F₂CH-O-、ClCH₂-O-、Cl₂CH-O-、CF₃CF₂-O-、CF₃CHF-O-、CHF₂CF₂-O-、CHF₂CHF-O-、CF₃CH₂-O- or CH ₂ClCH₂ -O-), and n1 represents 0, 1. 2,3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20.

In some embodiments of the present disclosure, each ring A ₁ independently represents a 1, 3-diazacyclobutene subunit, imidazolidine, pyrazolidine, piperazinylene, diazepane subunit, diazacyclooctane subunit, diazabicyclo [3.1.1] heptane subunit, diazabicyclo [2.2.1] heptane subunit, diazabicyclo [3.2.1] octane subunit, diazabicyclo [2.2.2] octane subunit, 2, 6-diazaspiro [3.3] heptane subunit, 2, 7-diazaspiro [3.5] nonane subunit, 2, 8-diazaspiro [4.5] decane subunit, 3, 9-diazaspiro [5.5] undecene subunit or octahydropyrrolo [3,4-C ] pyrrole subunit optionally substituted with n 1R _d1 groups, each R _d1 is independently deuterium, halogen (e.g., fluorine, chlorine, bromine or iodine), hydroxy, mercapto, nitro, amino, cyano, oxo, C _1-6 alkyl (e.g., C _1-5 alkyl), c _1-4 alkyl or C _1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C _1-6 alkyl, Halogenated C _1-6 alkyl (e.g., halogenated C _1-4 alkyl, such as F₃C-、FCH₂-、F₂CH-、ClCH₂-、Cl₂CH-、CF₃CF₂-、CF₃CHF-、CHF₂CF₂-、CHF₂CHF-、CF₃CH₂- or CH ₂ClCH₂-)、C_1-6 alkoxy (e.g., C _1-4 alkoxy, such as methoxy), Ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), Or a halogenated C _1-6 alkoxy group (e.g., a halogenated C _1-4 alkoxy group, such as F₃C-O-、FCH₂-O-、F₂CH-O-、ClCH₂-O-、Cl₂CH-O-、CF₃CF₂-O-、CF₃CHF-O-、CHF₂CF₂-O-、CHF₂CHF-O-、CF₃CH₂-O- or CH ₂ClCH₂ -O-), and n1 represents 0, 1. 2,3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20.

In some embodiments of the disclosure, each ring a ₂ herein independently represents a heterocyclylene group containing 1 nitrogen atom, for example a 4 to 30 membered heterocyclylene group, a 4 to 20 membered heterocyclylene group, or a 4 to 15 membered heterocyclylene group. Ring A ₂ is optionally substituted with n 4R _d4 groups, each R _d4 is independently deuterium, halogen, hydroxy, mercapto, nitro, amino, cyano, oxo, C _1-6 alkyl, deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, halogenated C _1-6 alkoxy or C _1-6 alkoxy, and n4 represents an integer of 0 to 20 (e.g., an integer of 0 to 10).

In some embodiments of the present disclosure, each ring a ₂ represents, independently of one another, a 4-to 30-membered heterocyclylene group containing 1 nitrogen atom (including 4-to 25-membered heterocyclylene group, 4-to 20-membered heterocyclylene group, 4-to 15-membered heterocyclylene group, and 5-to 20-membered heterocyclylene group). Ring A ₂ is optionally substituted with n 4R _d4 groups, each R _d4 being independently deuterium, halogen (e.g., fluorine, chlorine, bromine or iodine), hydroxy, mercapto, nitro, amino, cyano, oxo, C _1-6 alkyl (e.g., C _1-5 alkyl), C _1-4 alkyl or C _1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C _1-6 alkyl (for example perdeuterated C _1-6 alkyl, Perdeuterated C _1-5 alkyl or perdeuterated C _1-4 alkyl, e.g., CD ₃、CD₃CD₂-、CD₃CD₂CD₂ -, etc.), Halogenated C _1-6 alkyl (e.g., halogenated C _1-4 alkyl, such as F₃C-、FCH₂-、F₂CH-、ClCH₂-、Cl₂CH-、CF₃CF₂-、CF₃CHF-、CHF₂CF₂-、CHF₂CHF-、CF₃CH₂- or CH ₂ClCH₂-)、C_1-6 alkoxy (e.g., C _1-4 alkoxy, such as methoxy), Ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), Or a halogenated C _1-6 alkoxy group (e.g., a halogenated C _1-4 alkoxy group, such as F₃C-O-、FCH₂-O-、F₂CH-O-、ClCH₂-O-、Cl₂CH-O-、CF₃CF₂-O-、CF₃CHF-O-、CHF₂CF₂-O-、CHF₂CHF-O-、CF₃CH₂-O- or CH ₂ClCH₂ -O-), and n4 represents 0, 1. 2,3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20.

In some embodiments of the disclosure, each ring a ₂ represents independently of the others an azetidinyl, pyrrolidinylene, piperidinyl, dihydroxypiperidinyl, difluoropiperidinyl, azepanyl, azacyclooctyl, monoazacyclosubunit (e.g., 6 to 20 membered monoazacyclosubunit, such as 6-azabicyclo [3.1.1] heptanylidene, 3-azabicyclo [3.2.1] octanedioyl and quinuclidinyl) or a monoazaspirocyclic subunit (e.g., 5 to 20 membered monoazaspirocyclic subunit, such as 3-azaspiro [5.5] undecylidene and 7-azaspiro [3.5] nonanylidene), optionally substituted with n 4R _d4 groups, each R _d4 is independently of the other deuterium, Halogen (e.g. fluorine, chlorine, bromine or iodine), hydroxy, mercapto, nitro, amino, cyano, oxo, C _1-6 alkyl (e.g. C _1-5 alkyl, C _1-4 alkyl or C _1-3 alkyl, e.g. methyl), Ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C _1-6 alkyl (e.g., perdeuterated C _1-6 alkyl, perdeuterated C _1-5 alkyl or perdeuterated C _1-4 alkyl, e.g., CD ₃、CD₃CD₂-、CD₃CD₂CD₂ -, etc.), Halogenated C _1-6 alkyl (e.g., halogenated C _1-4 alkyl, such as F₃C-、FCH₂-、F₂CH-、ClCH₂-、Cl₂CH-、CF₃CF₂-、CF₃CHF-、CHF₂CF₂-、CHF₂CHF-、CF₃CH₂- or CH ₂ClCH₂-)、C_1-6 alkoxy (e.g., C _1-4 alkoxy, such as methoxy), Ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), Or a halogenated C _1-6 alkoxy group (e.g., a halogenated C _1-4 alkoxy group, such as F₃C-O-、FCH₂-O-、F₂CH-O-、ClCH₂-O-、Cl₂CH-O-、CF₃CF₂-O-、CF₃CHF-O-、CHF₂CF₂-O-、CHF₂CHF-O-、CF₃CH₂-O- or CH ₂ClCH₂ -O-), and _n 4 represents 0, 1. 2,3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20.

In some embodiments of the disclosure, R _w represents hydrogen or C _1-3 alkyl.

In some embodiments of the disclosure, R _w represents hydrogen.

In some embodiments of the present disclosure, R _w represents a C _1-3 alkyl group, such as methyl, ethyl, propyl, isopropyl, wherein the foregoing groups are optionally substituted with a substituent selected from deuterium, C _1-6 alkyl, deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, C _1-6 alkoxy, halogenated C _1-6 alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C _2-6 alkynyl, or C _2-6 alkenyl.

In some embodiments of the present disclosure, examples of R include, but are not limited to: Wherein the symbol indicates the point of attachment to R _c.

In some embodiments of the disclosure, R _c represents CR _c1R_c2, wherein R _c1 and R _c2 each independently represent H, deuterium, halogen (e.g., fluorine, chlorine, bromine, or iodine), optionally substituted straight or branched alkyl (e.g., optionally substituted straight or branched C _1-10 alkyl), optionally substituted cycloalkyl (e.g., optionally substituted C _3-30 cycloalkyl), optionally substituted heterocyclyl (e.g., optionally substituted 4-to 30-membered heterocyclyl), optionally substituted aryl (e.g., optionally substituted C _5-30 aryl), or optionally substituted heteroaryl (e.g., optionally substituted 5-to 30-membered heteroaryl).

In some embodiments of the disclosure, R _c represents a bond. When R _c represents a bond, ring B is directly attached to R.

In some embodiments of the disclosure, R _c represents CR _c1R_c2, wherein R _c1 and R _c2 each independently represent H, Deuterium, halogen (e.g. fluorine, chlorine, bromine or iodine), optionally substituted linear or branched C _1-10 alkyl (e.g. optionally substituted linear or branched C _1-6 alkyl or optionally substituted linear or branched C _1-3 alkyl), optionally substituted C _3-30 cycloalkyl (e.g. optionally substituted C _3-20 cycloalkyl or optionally substituted C _3-15 cycloalkyl), An optionally substituted C _5-30 aryl (e.g., an optionally substituted C _5-20 aryl, or an optionally substituted C _5-15 aryl), an optionally substituted 4 to 30 membered heterocyclyl (e.g., an optionally substituted 4 to 20 membered heterocyclyl, or an optionally substituted 4 to 15 membered heterocyclyl), or an optionally substituted 5 to 30 membered heteroaryl (e.g., an optionally substituted 5 to 20 membered heteroaryl, or an optionally substituted 5 to 15 membered heteroaryl). in some embodiments, examples of straight or branched C _1-10 alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, tert-pentyl, hexyl, heptyl, and octyl. In some embodiments, the straight or branched C _1-10 alkyl group is optionally substituted with one or more (e.g., 1-20, 1-15, 1-10, 1-6, 1-4, 1-3, 2-6, or 1) groups each independently selected from deuterium, halogen, amino, hydroxy, mercapto, cyano, nitro, oxo, C _1-6 alkyl, deuterated C _1-6 alkyl, A halo C _1-6 alkyl, C _1-6 alkoxy, halo C _1-6 alkoxy, C _2-6 alkynyl or C _2-6 alkenyl substituent. In some embodiments, examples of C _3-30 cycloalkyl include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, decalinyl, octahydropentacyclyl, octahydro-1H-indenyl, spirocycloalkyl (e.g., C ₅-C₁₅ spirocyclyl, C ₅-C₂₀ spirocyclyl, or C ₅-C₂₅ spirocyclyl, e.g., spiro [3.3] heptanyl, spiro [2.5] octyl, spiro [3.5] nonyl, spiro [3.5] nonenyl, spiro [4.4] nonyl, spiro [4.5] decyl, spiro [4.5] decenyl and spiro [5.5] undecyl), p-menthyl, m-menthyl, or bridged cycloalkyl (e.g., C ₆-C₁₅ bridged ring, C ₆-C₂₀ bridged ring, or C ₆-C₂₅ bridged ring, e.g., adamantyl), Adamantyl, norbornyl, bicyclo [2.2.1] heptyl, 2-oxo-bicyclo [2.2.1] heptyl, or bicyclo [2.2.1] heptenyl). In some embodiments, C _3-30 cycloalkyl is optionally substituted with one or more (e.g., 1-20, 1-15, 1-10, 1-6, 1-4, 1-3, 2-6, or 1) groups each independently selected from deuterium, halogen, hydroxy, mercapto, nitro, amino, cyano, oxo, C _1-6 alkyl, halogenated C _1-6 alkyl, Deuterated C _1-6 alkyl, C _1-6 alkoxy, deuterated C _1-6 alkoxy, halogenated C _1-6 alkoxy, substituents for C _2-6 alkenyl and C _2-6 alkynyl. In some embodiments, examples of 4-to 30-membered heterocyclyl groups include, but are not limited to, azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, tetrahydrofuranyl, tetrahydropyranyl, dihydropyranyl, tetrahydrothiophenyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, tetrahydropyridinyl, dihydroxypiperidinyl, difluoropiperidinyl, morpholinyl, thiomorpholinyl, azepanyl, dioxacyclohexyl, azepanyl, diazapanyl (e.g., 1, 4-diazapanyl, 4, 5-diazapanyl, and 1, 3-diazapanyl), Diazacyclooctane, bridged heterocyclyl (e.g., 6-to 20-membered bridged heterocyclyl, such as 6-azabicyclo [3.1.1] heptyl, 2, 5-diazabicyclo [2.2.1] heptyl, 3, 6-diazabicyclo [3.1.1] heptyl, 3-azabicyclo [3.2.1] octyl, 3, 8-diazabicyclo [3.2.1] octyl, 2, 5-diazabicyclo [2.2.2] octyl and quinine), and azaspirocyclyl (e.g., 5-to 20-membered azaspirocyclyl, such as 2, 6-diazaspiro [3.3] heptyl, 2, 7-diazaspiro [3.5] nonyl, 2, 8-diazaspiro [4.5] decyl, 3, 9-diazaspiro [5.5] undecyl, 3-azaspiro [5.5] undecyl and 7-azaspiro [3.5] nonanyl), or octahydropyrrolo [3,4-c ] pyrrolyl. In some embodiments, the 4-to 30-membered heterocyclyl is optionally substituted with one or more (e.g., 1-20, 1-15, 1-10, 1-6, 1-4, 1-3, 2-6, or 1) groups each independently selected from deuterium, halogen, hydroxy, mercapto, amino, cyano, oxo, C _1-6 alkyl, halo C _1-6 alkyl, deuterated C _1-6 alkyl, Substituents for C _1-6 alkoxy, halo C _1-6 alkoxy, C _2-6 alkenyl and C _2-6 alkynyl. In some embodiments, examples of C _5-30 aryl groups include, but are not limited to, phenyl or naphthyl. In some embodiments, the C _5-30 aryl is optionally substituted with one or more (e.g., 1-20, 1-15, 1-10, 1-6, 1-4, 1-3, 2-6, or 1) groups each independently selected from deuterium, halogen, hydroxy, mercapto, nitro, amino, cyano, C _1-6 alkyl, halogenated C _1-6 alkyl, Deuterated C _1-6 alkyl, C _1-6 alkoxy, halogenated C _1-6 alkoxy, C _2-6 alkenyl, and C _2-6 alkynyl. In some embodiments, examples of 5-to 30-membered heteroaryl groups include, but are not limited to, furyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, indolyl, isoindolyl, indolinyl, benzofuranyl, chromanyl, isobenzofuranyl, benzothienyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, benzo [2,1,3] oxadiazolyl, benzo [2,1,3] thiadiazolyl, Benzo [1,2,3] thiadiazolyl, 2-oxo-2, 3-dihydro-1H-benzo [ d ] imidazolyl, benzo [ b ] [1,4] oxazinyl, 3, 4-dihydro-2H-benzo [ b ] [1,4] oxazinyl, quinolinyl, isoquinolinyl, 1,2,3, 4-tetrahydroquinolinyl, naphthyridinyl, cinnolinyl, quinazolinyl, quinoxalinyl, 1,2,3, 4-tetrahydroquinoxalinyl, phthalazinyl, 5,6,7, 8-tetrahydro- [1,2,4] triazolo [4,3-a ] pyrazinyl, 4,5,6, 7-tetrahydrothieno [3,2-c ] pyridinyl, 5-oxo-6, 7-dihydrothieno [3,2-d ] pyrimidinyl, Thieno [2,3-d ] pyrimidinyl, thieno [3,2-d ] pyrimidinyl, isoxazolo [4,5-c ] pyridinyl, isoxazolo [4,5-d ] pyrimidinyl, pyrazolo [1,5-a ] pyridinyl, pyrazolo [1,5-a ] pyrimidinyl, imidazo [1,2-a ] pyridinyl, 1H-pyrrolo [3,2-b ] pyridinyl, 1H-pyrrolo [2,3-b ] pyridinyl, pyrrolo [2,1-b ] thiazolyl, imidazo [2,1-b ] thiazolyl, 5,6,7, 8-tetrahydrobenzo [4,5] thieno [2,3-d ] pyrimidinyl, Or 6, 7-dihydro-5H-cyclopenta [4,5] thieno [2,3-d ] pyrimidinyl. In some embodiments, the 5-to 30-membered heteroaryl group is optionally substituted with one or more (e.g., 1-20, 1-15, 1-10, 1-6, 1-4, 1-3, 2-6, or 1) groups each independently selected from deuterium, halogen, hydroxy, mercapto, nitro, amino, cyano, C _1-6 alkyl, halo C _1-6 alkyl, deuterated C _1-6 alkyl, Substituents for C _1-6 alkoxy, deuterated C _1-6 alkoxy, halogenated C _1-6 alkoxy, C _2-6 alkenyl, and C _2-6 alkynyl.

In some embodiments of the disclosure, m1 represents an integer of 1, and ring B represents a 4 to 30 membered heterocyclylene (e.g., a 4 to 20 membered heterocyclylene, or a 4 to 15 membered heterocyclylene), a C _3-30 cycloalkylene (e.g., a C _3-20 cycloalkylene, or a C _3-15 cycloalkylene), a, A C _5-30 arylene group (e.g., a C _5-20 arylene group, or a C _5-15 arylene group) or a 5 to 30 membered heteroarylene group (e.g., a 5 to 20 membered heteroarylene group, or a 5 to 15 membered heteroarylene group). Ring B is optionally substituted with n 2R _d2 groups, each R _d2 independently represents deuterium, C _1-6 alkyl (e.g., C _1-5 alkyl, c _1-4 alkyl or C _1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C _1-6 alkyl, Halogenated C _1-6 alkyl (e.g., halogenated C _1-4 alkyl, such as F₃C-、FCH₂-、F₂CH-、ClCH₂-、Cl₂CH-、CF₃CF₂-、CF₃CHF-、CHF₂CF₂-、CHF₂CHF-、CF₃CH₂- or CH ₂ClCH₂-)、C_1-6 alkoxy (e.g., C _1-4 alkoxy, such as methoxy), Ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), Halogenated C _1-6 alkoxy (e.g., halogenated C _1-4 alkoxy, such as F₃C-O-、FCH₂-O-、F₂CH-O-、ClCH₂-O-、Cl₂CH-O-、CF₃CF₂-O-、CF₃CHF-O-、CHF₂CF₂-O-、CHF₂CHF-O-、CF₃CH₂-O- or CH ₂ClCH₂ -O-) Halogen (e.g., fluorine, chlorine, bromine or iodine), amino, hydroxyl, mercapto, cyano, oxo, C _2-6 alkynyl (e.g., ethynyl) or C _2-6 alkenyl (e.g., vinyl), n2 represents an integer of 0, 1, 2,3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20.

In some embodiments, ring B represents a 4-to 30-membered heterocyclylene group, examples of which include, but are not limited to, 4-to 20-membered, 4-to 15-membered, 4-to 12-membered, 4-to 11-membered, 4-to 10-membered, 4-to 9-membered, 4-to 8-membered, 4-to 7-membered, 4-to 6-membered, 5-to 15-membered, and 5-to 9-membered heterocyclylene groups such as azetidinylene, oxetylene, pyrrolidinylene, imidazolidinylene, pyrazolidinylene, tetrahydrofuranylene, dihydropyranyl, tetrahydropyranyl, tetrahydrothiophenylene, tetrahydrothiopyranylene, oxazolidinylene, thiazolidinylene, Piperidylene, piperazinylene, morpholinylene, thiomorpholinylene, dioxanyl, azepanyl, azocyclooctyl, diazepan subunit (e.g., 1, 4-diazepan subunit, 4, 5-diazepan subunit, 1, 3-diazepan subunit), diazepan subunit, bridged heterocyclyl (e.g., 6-to 20-membered bridged heterocyclyl such as 6-azabicyclo [3.1.1] heptane subunit, 2, 5-diazabicyclo [2.2.1] heptane subunit, 3, 6-diazabicyclo [3.1.1] heptane subunit, 3-azabicyclo [3.2.1] octane subunit, 3, 8-diazabicyclo [3.2.1] octane subunit, 2, 5-diazabicyclo [2.2.2] octane subunit and quinuclidine group), diazaspirocyclic groups (e.g., 5 to 20 membered diazaspirocyclic groups such as 2, 6-diazaspiro [3.3] heptane subunit, 2, 7-diazaspiro [3.5] nonane subunit, 2, 8-diazaspiro [4.5] decane subunit, 3, 9-diazaspiro [5.5] undecene subunit, 3-azaspiro [5.5] undecene and 7-azaspiro [3.5] nonane subunit), or octahydropyrrolo [3,4-c ] pyrrole subunit. The heterocyclylene is optionally substituted with 0-20 (e.g., 1-20, 1-15, 1-10, 1-6, 1-4, 1-3, 2-6, or 1) groups each independently selected from deuterium, C _1-6 alkyl, deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, A substituent substituted with C _1-6 alkoxy, halo C _1-6 alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C _2-6 alkynyl or C _2-6 alkenyl.

In some embodiments, ring B represents C _3-30 cycloalkylene, examples of which include, but are not limited to, C _3-20 cycloalkylene, C _3-15 cycloalkylene, and C _3-11 cycloalkylene, such as cyclopropylene, Cyclobutylidene, cyclopentylidene, cyclohexylidene, cycloheptylidene, cyclooctylidene, decalin, octahydropentalene, octahydro-1H-indenylidene, 2, 3-dihydro-1H-indenylidene, spiroylidene (e.g., C ₅-C₂₀ spirospirocyclic alkyl and C _5-15 spirocyclic subunit, e.g., spiro [3.3] heptanylidene, spiro [2.5] octanedioxy, Spiro [3.5] nonane subunit, spiro [3.5] nonene subunit, spiro [4.4] nonane subunit, spiro [4.5] decane subunit, spiro [4.5] decene subunit, spiro [5.5] undecane subunit), p-menthene, m-menthene, or bridged cycloalkyl (e.g., C ₆-C₂₀ bridged cycloalkyl such as adamantylene, noradamantylene, bornylene, norbornylene, bicyclo [2.2.1] heptane subunit, 2-oxo bicyclo [2.2.1] heptane subunit, and bicyclo [2.2.1] heptene subunit). Cycloalkylene is optionally substituted with 0-20 (e.g., 1-20, 1-15, 1-10, 1-6, 1-4, 1-3, 2-6, or 1) groups each independently selected from deuterium, C _1-6 alkyl, deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, A substituent substituted with C _1-6 alkoxy, halo C _1-6 alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C _2-6 alkynyl or C _2-6 alkenyl.

In some embodiments, ring B represents C _5-30 arylene, examples of which include, but are not limited to, C _5-20 arylene, C _6-20 arylene, C ₅-₁₅ arylene, and C _6-15 arylene, such as phenylene or naphthylene. Arylene groups may optionally be substituted with 0-20 (e.g., 1-6, 1-4, 1-3, 2-6, or 1) substituents each independently selected from deuterium, C _1-6 alkyl, deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, C _1-6 alkoxy, halogenated C _1-6 alkoxy, halogen, amino, hydroxy, mercapto, cyano, C _2-6 alkynyl, or C _2-6 alkenyl.

In some embodiments, ring B represents a 5-to 30-membered heteroarylene group, examples of which include, but are not limited to, a 5-to 20-membered heteroarylene group, a 5-to 15-membered, a 5-to 10-membered, a 5-to 9-membered, a 5-to 8-membered, a 5-to 7-membered, and a 5-to 6-membered heteroarylene group, such as furanylene, oxazolylene, isoxazolylene, oxadiazolylene, thiophenylene, thiazolylene, isothiazolylene, thiadiazolylene, pyrrolylene, imidazolylene, pyrazolylene, triazolylene, pyridinyl, pyrimidinylene, pyridazinylene, pyrazinylene, triazinylene, indolylene, isoindolylene, indolinylene, benzofuranylene, Benzodihydropyran, isobenzofuranyl, benzothienyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, benzo [2,1,3] oxadiazolyl, benzo [2,1,3] thiadiazolyl, benzo [1,2,3] thiadiazolyl, 2-oxo-2, 3-dihydro-1H-benzo [ d ] imidazole subunit, benzo [ b ] [1,4] oxazinyl, 3, 4-dihydro-2H-benzo [ b ] [1,4] oxazinyl, quinolinyl, isoquinolinyl, 1,2,3, 4-tetrahydroquinolinyl, Naphthylidene, cinnolinyl, quinazolinylidene, quinoxalinylidene, 1,2,3, 4-tetrahydroquinoxalinylidene, phthalazinylidene, 5,6,7, 8-tetrahydro- [1,2,4] triazolo [4,3-a ] pyrazinylidene, 4,5,6, 7-tetrahydrothieno [3,2-c ] pyridine ylidene, 5-oxo-6, 7-dihydrothieno [3,2-d ] pyrimidine ylidene, thieno [2,3-d ] pyrimidine ylidene, thieno [3,2-d ] pyrimidine ylidene, isoxazolo [4,5-c ] pyridine ylidene, isoxazolo [4,5-c ] pyrimidine ylidene, isoxazolo [4,5-d ] pyrimidine ylidene, Pyrazolo [1,5-a ] pyridine subunit, pyrazolo [1,5-a ] pyrimidine subunit, imidazo [1,2-a ] pyridine subunit, 1H-pyrrolo [3,2-b ] pyridine subunit, 1H-pyrrolo [2,3-b ] pyridine subunit, pyrrolo [2,1-b ] thiazole subunit, imidazo [2,1-b ] thiazole subunit, 5,6,7, 8-tetrahydrobenzo [4,5] thieno [2,3-d ] pyrimidine subunit, or 6, 7-dihydro-5H-cyclopenta [4,5] thieno [2,3-d ] pyrimidine subunit. Heteroarylene is optionally substituted with 0 to 20 (e.g., 1 to 20, 1 to 15, 1 to 10, 1 to 6, 1 to 4, 1 to 3,2 to 6, or 1) groups each independently selected from deuterium, C _1-6 alkyl, deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, A substituent substituted with a C _1-6 alkoxy, halo C _{1- 6} alkoxy, halogen, amino, hydroxy, mercapto, cyano, C _2-6 alkynyl or C _2-6 alkenyl.

In some embodiments of the present disclosure, when m1 represents 0, i.e., ring B is absent, R _c is directly attached to ring C.

In some embodiments of the disclosure, ring C represents C _3-30 cycloalkyl (e.g., C _3-20 cycloalkyl, or C _3-15 cycloalkyl), 4 to 30 membered heterocyclyl (e.g., 4 to 20 membered heterocyclyl, or 4 to 15 membered heterocyclyl), C _5-30 aryl (e.g., C _5-20 aryl, or C _5-15 aryl), or 5 to 30 membered heteroaryl (e.g., 5 to 20 membered heteroaryl, or 5 to 15 membered heteroaryl). Ring C is optionally substituted with n 3R _d3 groups, each R _d3 is independently deuterium, C _1-6 alkyl, deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, C _1-6 alkoxy, halogenated C _1-6 alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C _2-6 alkynyl or C _2-6 alkenyl, and n4 represents an integer of 0,1,2,3, 4,5,6,7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20.

In some embodiments, ring C represents C _3-30 cycloalkyl, examples of which include, but are not limited to, C _3-20 cycloalkyl, C _3-15 cycloalkyl, and C _{3- 11} cycloalkyl, such as cyclopropyl, Cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, decalinyl, octahydropentalenyl, octahydro-1H-indenyl, spirocycloalkyl (e.g., C ₅-C₂₀ spirocyclic groups such as spiro [3.3] heptyl, spiro [2.5] octyl, spiro [3.5] nonyl, spiro [3.5] nonenyl, spiro [4.4] nonyl, spiro [4.5] decyl, spiro [4.5] decenyl, spiro [5.5] undecyl), p-menthyl, m-menthyl, Or bridged cycloalkyl (e.g., C ₆-C₂₀ bridged ring radicals such as adamantyl, noradamantyl, norbornyl, bicyclo [2.2.1] heptyl, 2-oxo-bicyclo [2.2.1] heptyl, or bicyclo [2.2.1] heptenyl). Cycloalkyl groups are optionally substituted with 0 to 20 (e.g., 1 to 20, 1 to 15, 1 to 10, 0 to 10, 1 to 6, 1 to 4, 1 to 3,2 to 6, or 1) groups each independently selected from deuterium, C _1-6 alkyl, deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, Substituents for C _1-6 alkoxy, halo C _1-6 alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C _2-6 alkynyl and C _2-6 alkenyl.

In some embodiments, ring C represents a 4-to 30-membered heterocyclyl group, examples of which include, but are not limited to, 4-to 20-membered, 4-to 15-membered, 4-to 12-membered, 4-to 11-membered, 4-to 10-membered, 4-to 9-membered, 4-to 8-membered, 4-to 7-membered, 4-to 6-membered, 5-to 15-membered, and 5-to 9-membered heterocyclyl groups, such as azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, tetrahydropyridinyl, dihydroxypiperidinyl, difluoropiperidinyl, morpholinyl, thiomorpholinyl, azepanyl, dioxanyl, azepanyl, azacyclooctyl, diazapanyl (e.g., 1, 4-diazapanyl, 4, 5-diazapanyl, 1, 3-diazapanyl), diazacyclooctyl, bridged heterocyclyl (e.g., 6-to 20-membered bridged heterocyclyl, such as 6-azabicyclo [3.1.1] heptyl, 2, 5-diazabicyclo [2.2.1] heptyl, 3, 6-diazabicyclo [3.1.1] heptyl, 3-azabicyclo [3.2.1] octyl, 3, 8-diazabicyclo [3.2.1] octyl, 2, 5-diazabicyclo [2.2.2] octanyl and quinuclidinyl), and azaspirocyclic groups (e.g., 5-to 20-membered azaspirocyclic groups such as 2, 6-diazaspiro [3.3] heptanyl, 2, 7-diazaspiro [3.5] nonanyl, 2, 8-diazaspiro [4.5] decane, 3, 9-diazaspiro [5.5] undecyl, 3-azaspiro [5.5] undecyl and 7-azaspiro [3.5] nonanyl), and octahydropyrrolo [3,4-c ] pyrrolyl. The heterocyclyl is optionally substituted with 0 to 20 (e.g., 1 to 20, 1 to 15, 1 to 10, 0 to 10, 1 to 6, 1 to 4, 1 to 3,2 to 6, or 1) groups each independently selected from deuterium, C _1-6 alkyl, deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, Substituents for C _1-6 alkoxy, halo C _1-6 alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C _2-6 alkynyl and C _2-6 alkenyl.

In some embodiments, ring C represents C _5-30 aryl, examples of which include, but are not limited to, C _5-20 aryl, C _6-20 aryl, C _5-15 aryl, and C _6-15 aryl, such as phenyl or naphthyl, optionally substituted with 0-20 (e.g., 1-7, 1-6, 0-7, 0-6, 1-4, 1-3, 2-6, or 1) substituents each independently selected from deuterium, C _1-6 alkyl, deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, C _1-6 alkoxy, halogenated C _{1- 6} alkoxy, halogen, amino, hydroxyl, mercapto, cyano, C _2-6 alkynyl, and C _2-6 alkenyl.

In some embodiments, ring C represents a 5-to 30-membered heteroaryl group, examples of which include, but are not limited to, a 5-to 20-membered heteroaryl group, a 5-to 15-membered, a 5-to 10-membered, a 5-to 9-membered, a 5-to 8-membered, a 5-to 7-membered, and a 5-to 6-membered heteroaryl group, such as furyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, indolyl, isoindolyl, indolinyl, benzofuranyl, chromanyl, isobenzofuranyl, benzothienyl, indolinyl, pyrazolyl, thiazolyl, and the like, Indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, benzo [2,1,3] oxadiazolyl, benzo [2,1,3] thiadiazolyl, benzo [1,2,3] thiadiazolyl, 2-oxo-2, 3-dihydro-1H-benzo [ d ] imidazolyl, benzo [ b ] [1,4] oxazinyl, 3, 4-dihydro-2H-benzo [ b ] [1,4] oxazinyl, quinolinyl, isoquinolinyl, 1,2,3, 4-tetrahydroquinolinyl, naphthyridinyl, cinnolinyl, quinazolinyl, quinoxalinyl, 1,2,3, 4-tetrahydroquinoxalinyl, Phthalazinyl, 5,6,7, 8-tetrahydro- [1,2,4] triazolo [4,3-a ] pyrazinyl, 4,5,6, 7-tetrahydrothieno [3,2-c ] pyridinyl, 5-oxo-6, 7-dihydrothieno [3,2-d ] pyrimidinyl, thieno [2,3-d ] pyrimidinyl, thieno [3,2-d ] pyrimidinyl, isoxazolo [4,5-c ] pyridinyl, isoxazolo [4,5-d ] pyrimidinyl, pyrazolo [1,5-a ] pyridinyl, pyrazolo [1,5-a ] pyrimidinyl, imidazo [1,2-a ] pyridinyl, 1H-pyrido [3,2-b ] pyridinyl, 1H-pyrrolo [2,3-b ] pyridinyl, pyrrolo [2,1-b ] thiazolyl, imidazo [2,1-b ] thiazolyl, 5,6,7, 8-tetrahydrobenzo [4,5] thieno [2,3-d ] pyrimidinyl, or 6, 7-dihydro-5H-cyclopenta [4,5] thieno [2,3-d ] pyrimidinyl. Heteroaryl groups are optionally substituted with 0 to 20 (e.g., 1 to 20, 1 to 15, 1 to 10, 0 to 10, 1 to 6, 1 to 4, 1 to 3,2 to 6, or 1) groups each independently selected from deuterium, C _1-6 alkyl, deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, Substituents for C _1-6 alkoxy, halo C _1-6 alkoxy, halogen, amino, hydroxy, mercapto, cyano, C _2-6 alkynyl and C _2-6 alkenyl.

In some embodiments of the present disclosure, a compound of formula (I)Examples of portions include, but are not limited to:

In some embodiments of the present disclosure, the compound of formula (I) is also a compound of formula (I-1): Wherein Z, R _a1、R_a2、R_a3、R_a4、(R_a5)_m, ring A ₁、(R_d1)_n1、R_c, ring B, (R _d2)_n2, m 1), Rings C and (R _d3)_n3) are as defined above for compounds of formula (I) and embodiments thereof, and wherein (I) R ₁ represents N (R _w) wherein R _w represents hydrogen or C _1-3 alkyl and R ₂ represents a bond, or R ₂ represents CH ₂ or C (O), or (ii) R ₁ represents a bond, and R ₂ represents N (R _w) wherein R _w represents hydrogen or C _1-3 alkyl, or R ₂ represents N (R _w) C (O) wherein R _w represents hydrogen or C _1-3 alkyl, or R ₂ represents-n=ch-, and the symbol indicates the point of attachment to R _c.

In some embodiments of the present disclosure, the compound of formula (I) is also a compound of formula (I-2): Wherein Z, R _a1、R_a2、R_a3、R_a4、(R_a5)_m, ring a ₁、(R_d1)_n1、R_c, ring B, (R _d2)_n2, m1, ring C and (R _d3)_n3) are as defined above for compounds of formula (I) and embodiments thereof, and wherein R _X represents NH, -n=ch-, or N (R _w) C (O), wherein R _w represents hydrogen or C _1-3 alkyl, and the symbol indicates the point of attachment to R _c.

In some embodiments of the present disclosure, the compound of formula (I) is also a compound of formula (I-3): Wherein Z, R _a1、R_a2、R_a3、R_a4、(R_a5)_m, ring A ₂、(R_d4)_n4、R_c, ring B, (R _d2)_n2, m1, ring C and (R _d3)_n3) are as defined above for compounds of formula (I) and embodiments thereof, and wherein R _y1 represents The symbol indicates the point of attachment to ring a ₂, and R ₂ represents N (R _w) C (O), wherein R _w represents hydrogen or C _1-3 alkyl, and the symbol indicates the point of attachment to R _c.

In some embodiments of the present disclosure, R _y1 represents-S-, -S-CH ₂ -or-S-CH ₂-CH₂ -.

In some embodiments of the present disclosure, the compound of formula (I) is also a compound of formula (I-4): Wherein Z, R _a1、R_a2、R_a3、R_a4、(R_a5)_m, R, ring B, (R _d2)_n2, m1, ring C and (R _d3)_n3) are as defined above for the compound of formula (I) and its various embodiments.

In some embodiments of the present disclosure, the compound of formula (I) is also a compound of formula (I-5): Wherein Z, R _a1、R_a2、R_a3、R_a4、(R_a5)_m, R, ring B, (R _d2)_n2, m1, ring C, and (Rd ₃)_n3) are as defined above for a compound of formula (I) and embodiments thereof, R _c1 represents H, deuterium, halogen (e.g., fluorine, chlorine, bromine, or iodine), or optionally substituted straight or branched C _1-10 alkyl (e.g., optionally substituted straight or branched C _1-6 alkyl or optionally substituted straight or branched C _1-3 alkyl), and R _c2 represents optionally substituted C _3-20 cycloalkyl (e.g., optionally substituted C _3-20 cycloalkyl, or optionally substituted C _3-15 cycloalkyl), optionally substituted C _5-30 aryl (e.g., optionally substituted C _5-20 aryl, or optionally substituted C _5-15 aryl), optionally substituted 4-to 30 membered heterocyclyl (e.g., optionally substituted 4-to 20 membered heterocyclyl, or optionally substituted 4-to 15 membered heterocyclyl), or optionally substituted 5-to 30 membered heteroaryl (e.g., optionally substituted 5-to 20 membered heteroaryl, or optionally substituted 5-to 15 membered heteroaryl).

In some embodiments of compounds of formula (I-5) of the present disclosure, R _c1 represents an optionally substituted, linear or branched C _1-10 alkyl group. Examples of straight or branched C _1-10 alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, tert-pentyl, hexyl, heptyl, and octyl. In some embodiments, the straight or branched C _1-10 alkyl group is optionally substituted with one or more (e.g., 1-20, 1-15, 1-10, 1-6, 1-4, 1-3, 2-6, or 1) substituents each independently selected from deuterium, halogen, amino, hydroxy, mercapto, cyano, nitro, oxo, C _1-6 alkyl, deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, C _1-6 alkoxy, halogenated C _1-6 alkoxy, C _2-6 alkynyl, or C _2-6 alkenyl.

In some embodiments of compounds of formula (I-5) of the present disclosure, R _c2 represents optionally substituted C _3-30 cycloalkyl (e.g., optionally substituted C _3-20 cycloalkyl, or optionally substituted C _3-15 cycloalkyl), An optionally substituted C _5-30 aryl (e.g., an optionally substituted C _5-20 aryl, or an optionally substituted C _5-15 aryl), an optionally substituted 4 to 30 membered heterocyclyl (e.g., an optionally substituted 4 to 20 membered heterocyclyl, or an optionally substituted 4 to 15 membered heterocyclyl), or an optionally substituted 5 to 30 membered heteroaryl (e.g., an optionally substituted 5 to 20 membered heteroaryl, or an optionally substituted 5 to 15 membered heteroaryl). In some embodiments, examples of C _3-30 cycloalkyl include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, decalinyl, octahydropentacyclyl, octahydro-1H-indenyl, spirocycloalkyl (e.g., C ₅-C₁₅ spirocyclyl, C ₅-C₂₀ spirocyclyl, or C ₅-C₂₅ spirocyclyl, e.g., spiro [3.3] heptanyl, spiro [2.5] octyl, spiro [3.5] nonyl, spiro [3.5] nonenyl, spiro [4.4] nonyl, spiro [4.5] decyl, spiro [4.5] decenyl and spiro [5.5] undecyl), p-menthyl, m-menthyl, or bridged cycloalkyl (e.g., C ₆-C₁₅ bridged ring, C ₆-C₂₀ bridged ring, or C ₆-C₂₅ bridged ring, e.g., adamantyl), Adamantyl, norbornyl, bicyclo [2.2.1] heptyl, 2-oxo-bicyclo [2.2.1] heptyl, or bicyclo [2.2.1] heptenyl). In some embodiments, C _3-30 cycloalkyl is optionally substituted with one or more (e.g., 1-20, 1-15, 1-10, 1-6, 1-4, 1-3, 2-6, or 1) groups each independently selected from deuterium, halogen, hydroxy, mercapto, nitro, amino, cyano, oxo, C _1-6 alkyl, halogenated C _1-6 alkyl, Deuterated C _1-6 alkyl, C _1-6 alkoxy, deuterated C _1-6 alkoxy, halogenated C _1-6 alkoxy, substituents for C _2-6 alkenyl and C _2-6 alkynyl. In some embodiments, examples of 4-to 30-membered heterocyclyl groups include, but are not limited to, azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, tetrahydrofuranyl, tetrahydropyranyl, dihydropyranyl, tetrahydrothiophenyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, tetrahydropyridinyl, dihydroxypiperidinyl, difluoropiperidinyl, morpholinyl, thiomorpholinyl, azepanyl, dioxacyclohexyl, azepanyl, diazapanyl (e.g., 1, 4-diazapanyl, 4, 5-diazapanyl, and 1, 3-diazapanyl), Diazacyclooctane, bridged heterocyclyl (e.g., 6-to 20-membered bridged heterocyclyl, such as 6-azabicyclo [3.1.1] heptyl, 2, 5-diazabicyclo [2.2.1] heptyl, 3, 6-diazabicyclo [3.1.1] heptyl, 3-azabicyclo [3.2.1] octyl, 3, 8-diazabicyclo [3.2.1] octyl, 2, 5-diazabicyclo [2.2.2] octyl and quinine), and azaspirocyclyl (e.g., 5-to 20-membered azaspirocyclyl, such as 2, 6-diazaspiro [3.3] heptyl, 2, 7-diazaspiro [3.5] nonyl, 2, 8-diazaspiro [4.5] decyl, 3, 9-diazaspiro [5.5] undecyl, 3-azaspiro [5.5] undecyl and 7-azaspiro [3.5] nonanyl), or octahydropyrrolo [3,4-c ] pyrrolyl. In some embodiments, the 4-to 30-membered heterocyclyl is optionally substituted with one or more (e.g., 1-20, 1-15, 1-10, 1-6, 1-4, 1-3, 2-6, or 1) groups each independently selected from deuterium, halogen, hydroxy, mercapto, amino, cyano, oxo, C _1-6 alkyl, halo C _1-6 alkyl, deuterated C _1-6 alkyl, Substituents for C _1-6 alkoxy, halo C _1-6 alkoxy, C _2-6 alkenyl and C _2-6 alkynyl. In some embodiments, examples of C _5-30 aryl groups include, but are not limited to, phenyl or naphthyl. In some embodiments, the C _5-30 aryl is optionally substituted with one or more (e.g., 1-20, 1-15, 1-10, 1-6, 1-4, 1-3, 2-6, or 1) groups each independently selected from deuterium, halogen, hydroxy, mercapto, nitro, amino, cyano, C _1-6 alkyl, halogenated C _1-6 alkyl, Deuterated C _1-6 alkyl, C _1-6 alkoxy, halogenated C _1-6 alkoxy, C _2-6 alkenyl, and C _2-6 alkynyl. In some embodiments, examples of 5-to 30-membered heteroaryl groups include, but are not limited to, furyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, indolyl, isoindolyl, indolinyl, benzofuranyl, chromanyl, isobenzofuranyl, benzothienyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, benzo [2,1,3] oxadiazolyl, benzo [2,1,3] thiadiazolyl, Benzo [1,2,3] thiadiazolyl, 2-oxo-2, 3-dihydro-1H-benzo [ d ] imidazolyl, benzo [ b ] [1,4] oxazinyl, 3, 4-dihydro-2H-benzo [ b ] [1,4] oxazinyl, quinolinyl, isoquinolinyl, 1,2,3, 4-tetrahydroquinolinyl, naphthyridinyl, cinnolinyl, quinazolinyl, quinoxalinyl, 1,2,3, 4-tetrahydroquinoxalinyl, phthalazinyl, 5,6,7, 8-tetrahydro- [1,2,4] triazolo [4,3-a ] pyrazinyl, 4,5,6, 7-tetrahydrothieno [3,2-c ] pyridinyl, 5-oxo-6, 7-dihydrothieno [3,2-d ] pyrimidinyl, Thieno [2,3-d ] pyrimidinyl, thieno [3,2-d ] pyrimidinyl, isoxazolo [4,5-c ] pyridinyl, isoxazolo [4,5-d ] pyrimidinyl, pyrazolo [1,5-a ] pyridinyl, pyrazolo [1,5-a ] pyrimidinyl, imidazo [1,2-a ] pyridinyl, 1H-pyrrolo [3,2-b ] pyridinyl, 1H-pyrrolo [2,3-b ] pyridinyl, pyrrolo [2,1-b ] thiazolyl, imidazo [2,1-b ] thiazolyl, 5,6,7, 8-tetrahydrobenzo [4,5] thieno [2,3-d ] pyrimidinyl, Or 6, 7-dihydro-5H-cyclopenta [4,5] thieno [2,3-d ] pyrimidinyl. In some embodiments, the 5-to 30-membered heteroaryl group is optionally substituted with one or more (e.g., 1-20, 1-15, 1-10, 1-6, 1-4, 1-3, 2-6, or 1) groups each independently selected from deuterium, halogen, hydroxy, mercapto, nitro, amino, cyano, C _1-6 alkyl, halo C _1-6 alkyl, deuterated C _1-6 alkyl, Substituents for C _1-6 alkoxy, deuterated C _1-6 alkoxy, halogenated C _1-6 alkoxy, C _2-6 alkenyl, and C _2-6 alkynyl.

In some embodiments of the present disclosure, the compound of formula (I) is also a compound of formula (II-1), a compound of formula (II-2), a compound of formula (II-3), or a compound of formula (II-4): Wherein Z, R _a1、R_a2、R_a3、R_a4、(R_a5)_m、R、R_c, ring B, (R _d2)_n2), ring C, (R _d3)_n3 and m1 are as defined above for the compounds of formula (I) and embodiments thereof.

Particularly preferred are the compounds of Table 1 of the present invention and salts (especially pharmaceutically acceptable salts, e.g., their hydrochloride salts), enantiomers, diastereomers, solvates or polymorphs thereof Compounds of formula (I')

The present disclosure provides a compound of formula (I'), or a salt (including pharmaceutically acceptable salts), stereoisomer (including enantiomers, diastereomers), solvate, isotopically enriched analog, or polymorph thereof: Wherein Z, R _a1、R_a2、R_a3、R_a4、(R_a5)_m、R₁、R₂, ring a ₁、(R_d1)_n1、R_e and R _f are as defined above for the compounds of formula (I') and embodiments thereof.

In some embodiments of compounds of formula (I') of the present disclosure, R _a1、R_a2、R_a3 and R _a4 are the same or different and each independently represent H, deuterium (i.e., D), halogen (e.g., fluorine, chlorine, bromine, or iodine), C _1-6 alkyl (e.g., C _1-3 alkyl, such as methyl, ethyl, or propyl), halogenated C _1-6 alkyl (e.g., halogenated C _1-4 alkyl, such as trifluoromethyl), deuterated C _1-6 alkyl, C _1-6 alkoxy (e.g., C _1-4 alkoxy, such as methoxy), deuterated C _1-6 alkoxy, or halogenated C _1-6 alkoxy (e.g., halogenated C _1-4 alkoxy, such as trifluoromethoxy). In some sub-embodiments of the present disclosure, R _a1、R_a2、R_a3 and R _a4 each independently represent H.

In some embodiments of the compounds of formula (I') of the present disclosure, Z represents C (O), CH ₂ or CD ₂.

In some embodiments of the compounds of formula (I') of the present disclosure, Z represents C (O).

In some embodiments of the compounds of formula (I') of the present disclosure, Z represents CH ₂.

In some embodiments of the compounds of formula (I') of the present disclosure, Z represents CD ₂.

In some embodiments of the compounds of formula (I') of the present disclosure, (R _a5)_m represents an isoindoline ring of formula (I) to which it is attached, optionally substituted with m R _a5, each R _a5 being the same or different and each independently representing deuterium, halogen (e.g., fluorine, Chlorine, bromine or iodine), hydroxyl, mercapto, nitro, amino, cyano, C _1-6 alkyl (e.g., C _1-5 alkyl, C _1-4 alkyl or C _1-3 alkyl, e.g., methyl), Ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C _1-6 alkyl (e.g. halogenated C _1-4 alkyl, e.g. F₃C-、FCH₂-、F₂CH-、ClCH₂-、Cl₂CH-、CF₃CF₂-、CF₃CHF-、CHF₂CF₂-、CHF₂CHF-、CF₃CH₂- or CH ₂ClCH₂ -) Deuterated C _1-6 alkyl (e.g., perdeuterated C _1-6 alkyl, perdeuterated C _1-5 alkyl, or perdeuterated C _1-4 alkyl, such as CD ₃、CD₃CD₂-、CD₃CD₂CD₂ -, etc.) C _1-6 alkoxy (e.g., C _1-4 alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), deuterated C _1-6 alkoxy, Halogenated C _1-6 alkoxy (e.g., halogenated C _1-4 alkoxy, such as F₃C-O-、FCH₂-O-、F₂CH-O-、ClCH₂-O-、Cl₂CH-O-、CF₃CF₂-O-、CF₃CHF-O-、CHF₂CF₂-O-、CHF₂CHF-O-、CF₃CH₂-O- or CH ₂ClCH₂-O-)、C_2-6 alkenyl (e.g., vinyl), a, C _2-6 alkynyl (e.g., ethynyl) or heterocyclyl (e.g., 4-to 30-membered heterocyclyl, 4-to 20-membered heterocyclyl, and 4-to 15-membered heterocyclyl), optionally substituted with one or more (e.g., 1-10, 1-6, 1-3, or 1) substituents independently selected from the group consisting of halogen, C _1-6 alkyl, and t-butoxycarbonyl, and m represents the integer 0, 1.2 or 3. In some sub-embodiments of the present disclosure, m represents an integer of 0,1, or 2. In some sub-embodiments of the present disclosure, each R _a5 is the same or different and each independently represents deuterium, halogen (e.g., fluorine, chlorine, bromine or iodine), hydroxy, mercapto, nitro, amino, cyano, C _1-4 alkyl (e.g., C _1-3 alkyl, e.g., methyl), Ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), Halogenated C _1-4 alkyl (e.g., halogenated C _1-3 alkyl, such as F₃C-、FCH₂-、F₂CH-、ClCH₂-、Cl₂CH-、CF₃CF₂-、CF₃CHF-、CHF₂CF₂-、CHF₂CHF-、CF₃CH₂- or CH ₂ClCH₂-)、C_1-4 alkoxy (e.g., C _1-3 alkoxy, such as methoxy), Ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), Halogenated C _1-4 alkoxy (e.g., halogenated C _1-3 alkoxy, e.g., F₃C-O-、FCH₂-O-、F₂CH-O-、ClCH₂-O-、Cl₂CH-O-、CF₃CF₂-O-、CF₃CHF-O-、CHF₂CF₂-O-、CHF₂CHF-O-、CF₃CH₂-O- or CH ₂ClCH₂ -O-) or 4-to 15-membered heterocyclyl (e.g., piperazinyl), optionally via one or more (e.g., 1-10, 1-6, 1-3, or 1) groups independently selected from halogen, halogen-substituted or halogen-substituted, C _1-6 alkyl and tert-butoxycarbonyl.

In embodiments of the compounds of formula (I') of the present disclosure, the number of substituents is in principle not subject to any restrictions or is automatically limited by the size of the building block.

In some embodiments of the compounds of formula (I') of the present disclosure, ring a ₁ represents a heterocyclylene group containing at least 2 nitrogen atoms, for example a 4 to 30 membered heterocyclylene group, a 4 to 20 membered heterocyclylene group or a 4 to 15 membered heterocyclylene group. Ring A ₁ is optionally substituted with n1 Rd ₁ groups, each Rd ₁ being independently deuterium, halogen, hydroxy, mercapto, nitro, amino, cyano, oxo, C _1-6 alkyl, deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, halogenated C _1-6 alkoxy or C _1-6 alkoxy, and n1 represents an integer of 0 to 20 (e.g., an integer of 0 to 10).

In some embodiments of the compounds of formula (I') of the present disclosure, ring a ₁ represents a 4-to 30-membered heterocyclylene group containing at least 2 nitrogen atoms (including 4-to 25-membered heterocyclylene group, 4-to 20-membered heterocyclylene group, 4-to 15-membered heterocyclylene group, and 5-to 20-membered heterocyclylene group). Ring A ₁ is optionally substituted with n 1R _d1 groups, each R _d1 being independently deuterium, halogen (e.g., fluorine, chlorine, bromine or iodine), hydroxy, mercapto, nitro, amino, cyano, oxo, C _1-6 alkyl (e.g., C _1-5 alkyl), C _1-4 alkyl or C _1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C _1-6 alkyl (for example perdeuterated C _1-6 alkyl, Perdeuterated C _1-5 alkyl or perdeuterated C _1-4 alkyl, e.g., CD ₃、CD₃CD₂-、CD₃CD₂CD₂ -, etc.), Halogenated C _1-6 alkyl (e.g., halogenated C _1-4 alkyl, such as F₃C-、FCH₂-、F₂CH-、ClCH₂-、Cl₂CH-、CF₃CF₂-、CF₃CHF-、CHF₂CF₂-、CHF₂CHF-、CF₃CH₂- or CH ₂ClCH₂-)、C_1-6 alkoxy (e.g., C _1-4 alkoxy, such as methoxy), Ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), Or a halogenated C _1-6 alkoxy group (e.g., a halogenated C _1-4 alkoxy group, such as F₃C-O-、FCH₂-O-、F₂CH-O-、ClCH₂-O-、Cl₂CH-O-、CF₃CF₂-O-、CF₃CHF-O-、CHF₂CF₂-O-、CHF₂CHF-O-、CF₃CH₂-O- or CH ₂ClCH₂ -O-), and n1 represents 0, 1. 2,3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20.

In some embodiments of the compounds of formula (I') of the present disclosure, ring A ₁ represents a1, 3-diazacyclobutene subunit, imidazolidinylene, pyrazolidinylene, piperazinylene, diazepanylene, diazacyclooctylene, diazabicyclo [3.1.1] heptanylene, diazabicyclo [2.2.1] heptanylene, diazabicyclo [3.2.1] octanylene, diazabicyclo [2.2.2] octanylene, 2, 6-diazaspiro [3.3] heptanylene, 2, 7-diazaspiro [3.5] nonane subunit, 2, 8-diazaspiro [4.5] decane subunit, 3, 9-diazaspiro [5.5] undecane subunit or octahydropyrrolo [3,4-c ] pyrrole subunit optionally substituted with n 1R _d1 groups, each R _d1 being independently deuterium, halogen (e.g. fluorine, chlorine, bromine or iodine), hydroxy, Mercapto, nitro, amino, cyano, oxo, C _1-6 alkyl (e.g. C _1-5 alkyl, C _1-4 alkyl or C _1-3 alkyl, e.g. methyl), Ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C _1-6 alkyl, Halogenated C _1-6 alkyl (e.g., halogenated C _1-4 alkyl, such as F₃C-、FCH₂-、F₂CH-、ClCH₂-、Cl₂CH-、CF₃CF₂-、CF₃CHF-、CHF₂CF₂-、CHF₂CHF-、CF₃CH₂- or CH ₂ClCH₂-)、C_1-6 alkoxy (e.g., C _1-4 alkoxy, such as methoxy), Ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), Or a halogenated C _1-6 alkoxy group (e.g., a halogenated C _1-4 alkoxy group, such as F₃C-O-、FCH₂-O-、F₂CH-O-、ClCH₂-O-、Cl₂CH-O-、CF₃CF₂-O-、CF₃CHF-O-、CHF₂CF₂-O-、CHF₂CHF-O-、CF₃CH₂-O- or CH ₂ClCH₂ -O-), and n1 represents 0, 1. 2,3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20.

In some embodiments of the compounds of formula (I') of the present disclosure, R ₁ represents a bond and R ₂ represents N (R _w), wherein R _w represents hydrogen or C _1-3 alkyl (e.g., methyl, ethyl, and propyl), wherein the above groups are optionally substituted with a substituent selected from deuterium, C _1-6 alkyl, deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, C _1-6 alkoxy, halogenated C _1-6 alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C _2-6 alkynyl, or C _2-6 alkenyl.

In some embodiments of compounds of formula (I') of the present disclosure, R ₁ represents N (R _w), wherein R _w represents hydrogen or is optionally substituted independently selected from one or more of optionally substituted aryl (e.g., C _5-30 aryl, C _1-3 alkyl substituted with substituents consisting of C _5-20 aryl and C _5-15 aryl) and optionally substituted heteroaryl (e.g., 5 to 30 membered heteroaryl, 5 to 20 membered heteroaryl, and 5 to 15 membered heteroaryl), and R ₂ represents a bond. In some embodiments of the compounds of formula (I') of the present disclosure, R _w represents hydrogen or C _1-3 alkyl (e.g., methyl, ethyl, and propyl), wherein the C _1-3 alkyl is optionally substituted with one or more substituents selected from the group consisting of: phenyl or naphthyl, optionally substituted with one or more (e.g., 1-7, 1-5, 1-4, 1-3, or 1) are each independently selected from halogen, amino, hydroxy, mercapto, cyano, oxo, C _1-6 alkyl, deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, C _1-6 alkoxy, Halo C _1-6 alkoxy, C _2-6 alkynyl and C _2-6 alkenyl, and furyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, and, Triazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, indolyl, isoindolyl, indolinyl, benzofuranyl, chromanyl, isobenzofuranyl, benzothienyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, benzo [2,1,3] oxadiazolyl, benzo [2,1,3] thiadiazolyl, benzo [1,2,3] thiadiazolyl, 2-oxo-2, 3-dihydro-1H-benzo [ d ] imidazolyl, benzo [ b ] [1,4] oxazinyl, 3, 4-dihydro-2H-benzo [ b ] [1,4] oxazinyl, Quinolinyl, isoquinolinyl, 1,2,3, 4-tetrahydroquinolinyl, naphthyridinyl, cinnolinyl, quinazolinyl, quinoxalinyl, 1,2,3, 4-tetrahydroquinoxalinyl, phthalazinyl, 5,6,7, 8-tetrahydro- [1,2,4] triazolo [4,3-a ] pyrazinyl, 4,5,6, 7-tetrahydrothieno [3,2-c ] pyridinyl, 5-oxo-6, 7-dihydrothieno [3,2-d ] pyrimidinyl, thieno [2,3-d ] pyrimidinyl, thieno [3,2-d ] pyrimidinyl, isoxazolo [4,5-c ] pyrimidinyl, isoxazolo [4,5-d ] pyrimidinyl, Pyrazolo [1,5-a ] pyridinyl, pyrazolo [1,5-a ] pyrimidinyl, imidazo [1,2-a ] pyridinyl, 1H-pyrrolo [3,2-b ] pyridinyl, 1H-pyrrolo [2,3-b ] pyridinyl, pyrrolo [2,1-b ] thiazolyl, imidazo [2,1-b ] thiazolyl, 5,6,7, 8-tetrahydrobenzo [4,5] thieno [2,3-d ] pyrimidinyl, and 6, 7-dihydro-5H-cyclopenta [4,5] thieno [2,3-d ] pyrimidinyl, optionally substituted with one or more (e.g., 1-10, 1-7, 1-5, 1-4, 1-3 or 1) are each independently selected from halogen, amino, hydroxy, mercapto, cyano, oxo, C _1-6 alkyl, deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, C _1-6 alkoxy, Substituents substituted with halo C _1-6 alkoxy, C _2-6 alkynyl and C _2-6 alkenyl, and/or

In some embodiments of the compounds of formula (I') of the present disclosure, R ₁ represents N (R _w), wherein R _w represents H orAnd R ₂ represents a bond.

In some embodiments of the compounds of formula (I') of the present disclosure, R _e represents a bond. In some embodiments of the compounds of formula (I') of the present disclosure R _e represents C (O) O.

In some embodiments of the compounds of formula (I') of the present disclosure, R _e represents the structure of the formula: Wherein R _e1 represents C (O), CH ₂ or haloCH ₂, ring D represents arylene, (R _e2)_m2 represents that ring D is optionally substituted by m 2R _e2 groups, each R _e2 independently represents deuterium, c _1-6 alkyl, deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, C _1-6 alkoxy, halogenated C _1-6 alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C _2-6 alkynyl or C _2-6 alkenyl, and m2 represents an integer of 0 to 20, and ring E represents a nitrogen-containing heterocyclylene group, m4 represents an integer of 0 or 1, (R _e3)_m3 represents a ring E optionally substituted with m 3R _e3 groups, each R _e3 independently represents deuterium, c _1-6 alkyl, deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, C _1-6 alkoxy, halogenated C _1-6 alkoxy, Halogen, amino, hydroxy, mercapto, cyano, oxo, C _2-6 alkynyl or C _2-6 alkenyl, and m3 represents an integer from 0 to 20, and the symbol # indicates the point of attachment to R _f.

In some embodiments of the compounds of formula (I') of the present disclosure, ring D represents C _5-30 arylene, examples of which include, but are not limited to, C _5-20 arylene, C _6-20 arylene, C _5-15 arylene, and C _6-15 arylene, such as phenylene or naphthylene. Arylene is optionally substituted with m2 (e.g., an integer from 0 to 20 or an integer from 0 to 10, such as 1 to 6, 1 to 4, 1 to 3,2 to 6, or 1) each independently selected from deuterium, C _1-6 alkyl, deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, C _1-6 alkoxy, halogenated C _1-6 alkoxy, halogen, amino, hydroxy, mercapto, cyano, C _2-6 alkynyl, or substituent R _e2 of C _2-6 alkenyl.

In some embodiments of the compounds of formula (I') of the present disclosure, m4 represents an integer of 1, ring E represents a 4-to 30-membered nitrogen-containing heterocyclic group, examples of which include, but are not limited to, 4-to 20-membered, 4-to 15-membered, 4-to 12-membered, 4-to 11-membered, 4-to 10-membered, 4-to 9-membered, 4-to 8-membered, 4-to 7-membered, 4-to 6-membered, 5-to 15-membered, and 5-to 9-membered nitrogen-containing heterocyclic groups such as azetidine, pyrrolidinylene, imidazolidinylene, pyrazolidinylene, piperidylene, piperazinylene, tetrahydropyridinylene, dihydroxypiperidylene, difluoropiperidylene, Azacycloheptyl, azacyclooctyl, diazepan subunit (e.g., 1, 4-diazepan subunit, 4, 5-diazepan subunit, 1, 3-diazepan subunit), diazepan subunit, azetidine subunit (e.g., 6-to 20-membered azetidine, e.g., 6-azabicyclo [3.1.1] heptane subunit, 2, 5-diazabicyclo [2.2.1] heptane subunit, 3, 6-diazabicyclo [3.1.1] heptane subunit, 3-azabicyclo [3.2.1] octane subunit, 3, 8-diazabicyclo [3.2.1] octane subunit, 2, 5-diazabicyclo [2.2.2] octane subunit, and quinuclidine), Azaspirocyclic groups (e.g., 5-to 20-membered azaspirocyclic groups such as 2, 6-diazaspiro [3.3] heptane subunit, 2, 7-diazaspiro [3.5] nonane subunit, 2, 8-diazaspiro [4.5] decane subunit, 3, 9-diazaspiro [5.5] undecane subunit, 3-azaspiro [5.5] undecane subunit and 7-azaspiro [3.5] nonane subunit), or octahydropyrrolo [3,4-c ] pyrrole subunit. The nitrogen-containing heterocyclylene is optionally substituted with m3 (e.g., 0-20, such as 1-20, 1-15, 1-10, 1-6, 1-4, 1-3, 2-6, or 1) groups each independently selected from deuterium, C _1-6 alkyl, deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, A substituent R _e3 substituted with C _1-6 alkoxy, halo C _1-6 alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C _2-6 alkynyl or C _2-6 alkenyl.

In some embodiments of the compounds of formula (I') of the present disclosure, R _e representsWherein the symbol # indicates the point of attachment to R _f.

In some embodiments of the compounds of formula (I') of the present disclosure, R _f represents C _1-10 alkyl, examples of which include, but are not limited to, for example, C _1-10 alkyl, C _1-9 alkyl, C _1-8 alkyl, C _1-7 alkyl, C _1-6 alkyl, C _1-5 alkyl, C _1-4 alkyl, C _1-3 alkyl, C _1-2 alkyl and methyl, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, tert-pentyl, hexyl, heptyl, octyl, nonyl and decyl. c _1-10 alkyl is optionally substituted with one or more (e.g., 1-20, such as 1-18, 1-15, 1-10, 1-6, 1-5, 1-4, 1-3, 2-6, or 1) substituents independently selected from the group consisting of halogen (e.g., fluorine, chlorine, bromine, or iodine), optionally substituted aryl (e.g., optionally substituted C _5-30 aryl, An optionally substituted C _5-20 aryl, an optionally substituted C _5-15 aryl), an optionally substituted heteroaryl (e.g., an optionally substituted 5 to 30 membered heteroaryl, an optionally substituted 5 to 20 membered heteroaryl, or an optionally substituted 5 to 15 membered heteroaryl), an optionally substituted heterocyclyl (e.g., an optionally substituted 4 to 30 membered heterocyclyl, an optionally substituted 4 to 20 membered heterocyclyl, or an optionally substituted 4 to 15 membered heterocyclyl), Optionally substituted cycloalkyl (e.g., optionally substituted C _3-30 cycloalkyl), Optionally substituted C _3-20 cycloalkyl, or optionally substituted C _3-15 cycloalkyl) and NR ₃R₄, wherein R ₃ and R ₄ each independently represent H, C _1-3 alkyl or optionally substituted cycloalkyl (e.g., optionally substituted C _3-30 cycloalkyl, optionally substituted C _3-20 cycloalkyl, or optionally substituted C _3-15 cycloalkyl). In some embodiments, examples of aryl groups include, but are not limited to, C _5-30 aryl, C _{5- 20} aryl, C _6-20 aryl, C _5-15 aryl and C _6-15 aryl, such as phenyl or naphthyl. In some embodiments, the aryl group is optionally substituted with one or more (e.g., 1-20, 1-15, 1-10, 1-7, 1-6, 1-4, 1-3, 2-6, or 1) groups each independently selected from halogen, amino, hydroxy, mercapto, cyano, oxo, C _1-6 alkyl, deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, Substituents for C _1-6 alkoxy, halo C _1-6 alkoxy, C _2-6 alkynyl and C _2-6 alkenyl. in some embodiments, examples of heteroaryl groups include, but are not limited to, 5-to 30 membered heteroaryl, 5-to 20 membered heteroaryl, 5-to 15-membered, 5-to 10-membered, 5-to 9-membered, 5-to 8-membered, 5-to 7-membered, and 5-to 6-membered heteroaryl groups such as furyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, indolyl, isoindolyl, indolinyl, benzofuranyl, chromanyl, isobenzofuranyl, benzothienyl, indazolyl, benzofuranyl, Benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, benzo [2,1,3] oxadiazolyl, benzo [2,1,3] thiadiazolyl, benzo [1,2,3] thiadiazolyl, 2-oxo-2, 3-dihydro-1H-benzo [ d ] imidazolyl, benzo [ b ] [1,4] oxazinyl, 3, 4-dihydro-2H-benzo [ b ] [1,4] oxazinyl, quinolinyl, isoquinolinyl, 1,2,3, 4-tetrahydroquinolinyl, naphthyridinyl, cinnolinyl, quinazolinyl, quinoxalinyl, 1,2,3, 4-tetrahydroquinoxalinyl, phthalazinyl, 5,6,7, 8-tetrahydro- [1,2,4] triazolo [4,3-a ] pyrazinyl, 4,5,6, 7-tetrahydrothieno [3,2-c ] pyridinyl, 5-oxo-6, 7-dihydrothieno [3,2-d ] pyrimidinyl, thieno [2,3-d ] pyrimidinyl, thieno [3,2-d ] pyrimidinyl, isoxazolo [4,5-c ] pyrimidinyl, isoxazolo [4,5-d ] pyrimidinyl, pyrazolo [1,5-a ] pyridinyl, pyrazolo [1,5-a ] pyrimidinyl, imidazo [1,2-a ] pyridinyl, 1H-pyrrolo [3,2-b ] pyridinyl, 1H-pyrrolo [2,3-b ] pyridinyl, pyrrolo [2,1-b ] thiazolyl, imidazo [2,1-b ] thiazolyl, 5,6,7, 8-tetrahydrobenzo [4,5] thieno [2,3-d ] pyrimidinyl, or 6, 7-dihydro-5H-cyclopenta [4,5] thieno [2,3-d ] pyrimidinyl. In some embodiments, the heteroaryl is optionally substituted with one or more (e.g., 1-20, 1-15, 1-10, 1-7, 1-6, 1-4, 1-3, 2-6, or 1) groups each independently selected from halogen, amino, hydroxy, mercapto, cyano, oxo, C _1-6 alkyl, deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, Substituents for C _1-6 alkoxy, halo C _1-6 alkoxy, C _2-6 alkynyl and C _2-6 alkenyl. In some embodiments, examples of heterocyclyl include, but are not limited to, 4-to 30-membered heterocyclyl, 4-to 20-membered heterocyclyl, 4-to 15-membered, 4-to 12-membered, 4-to 11-membered, 4-to 10-membered, 4-to 9-membered, 4-to 8-membered, 4-to 7-membered, 4-to 6-membered, 5-to 15-membered, and 5-to 9-membered heterocyclyl, such as azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, tetrahydrofuranyl, tetrahydropyranyl, dihydropyranyl, tetrahydrothiophenyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, tetrahydropyridinyl, Dihydroxypiperidinyl, difluoropiperidinyl, morpholinyl, thiomorpholinyl, azepanyl, dioxapanyl, azepanyl, azapanyl, diazapanyl (e.g., 1, 4-diazapanyl, 4, 5-diazapanyl, and 1, 3-diazapanyl), diazapanyl, bridged heterocyclyl (e.g., 6-to 20-membered bridged heterocyclyl such as 6-azabicyclo [3.1.1] panyl, 2, 5-diazabicyclo [2.2.1] panyl, 3, 6-diazabicyclo [3.1.1] panyl, 3-azabicyclo [3.2.1] octanyl), 3, 8-diazabicyclo [3.2.1] octanyl, 2, 5-diazabicyclo [2.2.2] octanyl and quinuclidinyl), and azaspirocyclic groups (e.g., 5 to 20 membered azaspirocyclic groups such as 2, 6-diazaspiro [3.3] heptanyl, 2, 7-diazaspiro [3.5] nonanyl, 2, 8-diazaspiro [4.5] decane, 3, 9-diazaspiro [5.5] undecyl, 3-azaspiro [5.5] undecyl and 7-azaspiro [3.5] nonanyl), or octahydropyrrolo [3,4-c ] pyrrolyl. In some embodiments, the heterocyclyl is optionally substituted with one or more (e.g., 1-20, 1-15, 1-10, 1-6, 1-4, 1-3, 2-6, or 1) groups each independently selected from halogen, amino, hydroxy, mercapto, cyano, oxo, C _1-6 alkyl, deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, Substituents for C _1-6 alkoxy, halo C _1-6 alkoxy, C _2-6 alkynyl, C _2-6 alkenyl, t-butoxycarbonyl and R _h. R _h represents an optionally substituted C _5-15 aryl group, examples of which include, but are not limited to, C _5-12 aryl, C _6-12 aryl, and C _6-10 aryl, such as phenyl or naphthyl. The C _5-15 aryl is optionally substituted with one or more (e.g., 1-10, 1-6, 1-4, 1-3, 2-6, or 1) substituents selected from halogen, C _1-6 alkyl, and C _1-6 alkoxy. In some embodiments, examples of cycloalkyl groups include, but are not limited to, C _3-30 cycloalkyl, C _3-20 cycloalkyl, C _3-15 cycloalkyl, C _3-11 cycloalkyl, C _5-15 cycloalkyl and C _7-15 cycloalkyl, for example cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, decalinyl, octahydropentacyclyl, octahydro-1H-indenyl, spirocycloalkyl (for example C ₅-C₁₅ spirocyclyl, spirocycloalkyl), C ₅-C₂₀ spirocyclic groups or C ₅-C₂₅ spirocyclic groups, for example spiro [3.3] heptyl, spiro [2.5] octyl, spiro [3.5] nonyl, spiro [3.5] nonenyl, spiro [4.4] nonyl, spiro [4.5] decyl, spiro [4.5] decenyl and spiro [5.5] undecyl), p-menthyl, m-menthyl, or bridged cycloalkyl (for example C ₆-C₁₅ bridged cyclic group, C ₆-C₂₀, C ₆-C₂₅ and C ₇-C₁₅ bridged ring radicals, such as adamantyl, noradamantyl, norbornyl, bicyclo [2.2.1] heptanyl, 2-oxo-bicyclo [2.2.1] heptanyl or bicyclo [2.2.1] heptenyl). In some embodiments, the cycloalkyl is optionally substituted with one or more (e.g., 1-20, 1-15, 1-10, 1-6, 1-4, 1-3, 2-6, or 1) groups each independently selected from halogen, amino, hydroxy, mercapto, cyano, oxo, C _1-6 alkyl, deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, C _1-6 alkoxy, halo C _1-6 alkoxy, C _2-6 alkynyl, C _2-6 alkenyl, T-butoxycarbonyl and R _h, wherein R _h represents an optionally substituted C _5-15 aryl group, examples of which include, but are not limited to, C _5-12 aryl, C _6-12 aryl and C _6-10 aryl, such as phenyl or naphthyl, wherein the C _5-15 aryl is optionally substituted with one or more (e.g. 1-10, 1-6, 1-5, 1-4, 1-3, 2-6 or 1) groups selected from halogen, Substituents for C _1-6 alkyl and C _1-6 alkoxy.

In some embodiments, R ₃ and R4 each independently represent H, C _1-3 alkyl or optionally substituted cycloalkyl (e.g., optionally substituted C _3-30 cycloalkyl, optionally substituted C _3-20 cycloalkyl, or optionally substituted C _3-15 cycloalkyl). In some embodiments, examples of cycloalkyl groups include, but are not limited to, C _3-30 cycloalkyl, C _3-20 cycloalkyl, C _3-15 cycloalkyl, C _5-15 cycloalkyl, and C _7-15 cycloalkyl groups, such as cyclopropyl, Cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, hexenyl, cycloheptyl, cyclooctyl, decalinyl, octahydropentalenyl, octahydro-1H-indenyl, spirocyclic alkyl (e.g., C ₅-C₁₅ spirocyclic group, C ₅-C₂₀ spirocyclic group, or C ₅-C₂₅ spirocyclic group, such as spiro [3.3] heptyl, Spiro [2.5] octyl, spiro [3.5] nonyl, spiro [3.5] nonenyl, spiro [4.4] nonyl, spiro [4.5] decyl, spiro [4.5] decenyl and spiro [5.5] undecyl), p-menthyl, m-menthyl, or bridged cycloalkyl (e.g., C ₆-C₁₅ bridged ring, C ₆-C₂₀ bridged ring, C ₆-C₂₅ bridged ring and C ₇-C₁₅ bridged ring, e.g., adamantyl, Adamantyl, norbornyl, bicyclo [2.2.1] heptyl, 2-oxo-bicyclo [2.2.1] heptyl, or bicyclo [2.2.1] heptenyl). In some embodiments, the cycloalkyl is optionally substituted with one or more (e.g., 1-20, 1-15, 1-10, 1-6, 1-4, 1-3, 2-6, or 1) groups each independently selected from halogen, amino, hydroxy, mercapto, cyano, oxo, C _1-6 alkyl, deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, C _1-6 alkoxy, halo C _1-6 alkoxy, C _2-6 alkynyl, C _{2- 6} alkenyl, T-butoxycarbonyl and R _h, wherein R _h represents an optionally substituted C _5-15 aryl group, examples of which include, but are not limited to, C _5-12 aryl, C _6-12 aryl and C _6-10 aryl, such as phenyl or naphthyl, wherein the C _5-15 aryl is optionally substituted with one or more (e.g. 1-10, 1-6, 1-5, 1-4, 1-3, 2-6 or 1) groups selected from halogen, Substituents for C _1-6 alkyl and C _1-6 alkoxy. In some embodiments, R ₃ represents H, and R ₄ represents a bridged cycloalkyl (e.g., C ₆-C₁₅ bridged ring, C ₆-C₂₀ bridged ring, a, C ₆-C₂₅ and C ₇-C₁₅ bridged ring groups, for example adamantyl, noradamantyl, norbornyl, bicyclo [2.2.1] heptyl, 2-oxo-bicyclo [2.2.1] heptyl or bicyclo [2.2.1] heptenyl, optionally substituted with one or more (for example 1-20, 1-15, 1-10, 1-6, 1-4, 1-3, 2-6 or 1) are each independently selected from halogen, amino, hydroxy, mercapto, cyano, oxo, C _1-6 alkyl, deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, C _1-6 alkoxy, Halo C _1-6 alkoxy, C _2-6 alkynyl, C _2-6 alkenyl, and t-butoxycarbonyl.

In some embodiments of the compounds of formula (I') of the present disclosure, examples of R _f include, but are not limited to, methyl, isopropyl, tert-butyl,

Particularly preferred are the compounds of Table 2 of the present invention and salts (especially pharmaceutically acceptable salts, e.g., their hydrochloride salts), enantiomers, diastereomers, solvates or polymorphs thereof: the compounds of the present invention of Table 2 Other forms of the compounds (including salts, enantiomers, stereoisomers, solvates, isotopically enriched analogues or polymorphs of the compounds)

The compounds of the present disclosure have the structure of any of formula (I), formula (I-1), formula (I-2), formula (I-3), formula (I-4), formula (I-5), formula (II-1), formula (II-2), formula (II-3), formula (II-4), or formula (I'). Unless otherwise indicated, when referring to compounds of the present disclosure, it is meant to include compounds of any of formula (I), formula (I-1), formula (I-2), formula (I-3), formula (I-4), formula (I-5), formula (II-1), formula (II-2), formula (II-3), formula (II-4) or formula (I'), as well as specific compounds falling within the scope of these formulas.

It will be appreciated that the compounds of the present disclosure, including compounds of formula (I), formula (I-1), formula (I-2), formula (I-3), formula (I-4), formula (I-5), formula (II-1), formula (II-2), formula (II-3), formula (II-4), or formula (I'), may have a stereochemical configuration and thus may exist in more than one stereoisomeric form. The disclosure also relates to optically enriched compounds having a steric configuration, such as greater than 90% ee, such as about 95% ee or 97% ee, or greater than 99% ee, and mixtures thereof, including racemic mixtures. As used herein, "optically enriched" means that a mixture of enantiomers consists of a significantly greater proportion of one enantiomer, and can be described by enantiomeric excess (ee%). Purification of the isomers and separation of the isomer mixtures may be accomplished by standard techniques known in the art (e.g., column chromatography, preparative TLC, preparative HPLC, asymmetric synthesis (e.g., by using chiral intermediates), chiral resolution, and/or the like).

In some embodiments, also provided are polymorphic forms of a compound of the disclosure (including formula (I), formula (I-1), formula (I-2), formula (I-3), formula (I-4), formula (I-5), formula (II-1), formula (II-2), formula (II-3), formula (II-4), or formula (I') or a salt of a compound of the disclosure. Salts of the compounds of the present disclosure may be pharmaceutically acceptable salts, including but not limited to hydrohalates (including hydrochloride, hydrobromide), sulfate, maleate, sulfonate, citrate/citrate, lactate, lactobionate, L-tartrate, fumarate, L-malate, L-lactate, alpha-ketoglutarate, hippurate, D-glucuronate, D-gluconate, alpha-D-glucoheptonate, glycolate, mucinate, L-ascorbate, orotate, picrate, glycinate, alaninate, arginate, cinnamate, laurate, pamoate, sebacate, benzenesulfonate, methanesulfonate, ethanesulfonate, ethanedisulfonate, formate, acetate, 2-dichloroacetate, trimethylacetate, propionate valerate, palmitate, triphenylacetate, 2-ethyl-succinate, iodate, nicotinate, L-pyroglutamate, L-proline, ferulate, 2-hydroxyethanesulfonate, nitrate, gentisate, cholate, salicylate, terephthalate, glutarate, adipate, stearate, oleate, undecylenate, camphorsulfonate, dodecylsulfonate, phosphate, thiocyanate, dihydrogen phosphate, pyrophosphate, metaphosphate, oxalate, carbonate, malonate, benzoate, mandelate, succinate, pyruvate, p-chlorobenzenesulfonate, 1, 5-naphthalenedisulfonate, 3-hydroxy-2-naphthoate, 1-hydroxy-2-naphthoate, 2-naphthalene sulfonate, trifluoroacetate, glycolate, p-toluene sulfonate, or the like. The compounds of the present disclosure can exist in a pharmaceutically acceptable solvent such as water, ethanol, and the like, in the form of non-solvates or solvates. In some embodiments, compounds of the present disclosure may be prepared as prodrugs or prodrugs. The prodrug can be converted into the parent drug in the body to act. In some embodiments, isotopically-labeled compounds of the present disclosure are also provided, examples of isotopes including deuterium (D or ² H). III pharmaceutical composition/formulation

In some embodiments, the present disclosure provides a pharmaceutical composition comprising as an active ingredient a compound of the present disclosure (including formula (I), formula (I-1), formula (I-2), formula (I-3), formula (I-4), formula (I-5), formula (II-1), formula (II-2), formula (II-3), formula (II-4), or formula (I') or a pharmaceutically acceptable salt, solvate, isotopically enriched analog, polymorph, stereoisomer (including enantiomer), or mixture of stereoisomers thereof, and at least one pharmaceutically acceptable carrier.

In some embodiments, pharmaceutically acceptable carriers include, but are not limited to, fillers, stabilizers, dispersants, suspending agents, diluents, excipients, thickeners, colorants, solvents, or encapsulating materials. The carrier is compatible with the other ingredients of the formulation, including the compounds useful in this disclosure, and not deleterious to the patient, and must be "acceptable". Some examples of materials for pharmaceutically acceptable carriers include sugars such as lactose, dextrose, and sucrose, starches such as corn starch and potato starch, celluloses and derivatives thereof such as sodium carboxymethyl cellulose, ethyl cellulose, and cellulose acetate, powdered tragacanth, malt, gelatin, talc, excipients such as cocoa butter and suppository waxes, oils such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil, and soybean oil, glycols such as propylene glycol, polyols such as glycerol, sorbitol, mannitol, and polyethylene glycols, esters such as ethyl oleate and ethyl laurate, agar, buffers such as magnesium hydroxide and aluminum hydroxide, surfactant phosphate buffer solutions, polyoxyethylene, polyvinylpyrrolidone, polyacrylamide, poloxamers, and other non-toxic compatible materials used in pharmaceutical formulations.

The pharmaceutical compositions described in the present disclosure further comprise at least one second therapeutic agent, such as an anticancer agent. The second therapeutic agent may treat a disease or disorder described in the present disclosure in combination with a compound of formula (I) (or a compound of formula (I-1), formula (I-2), formula (I-3), formula (I-4), formula (I-5), formula (II-1), formula (II-2), formula (II-3), formula (II-4), or formula (I'). The second therapeutic agent includes, but is not limited to, a chemotherapeutic agent, an immunotherapeutic agent, a gene therapeutic agent, and the like.

The pharmaceutical composition comprising the compound of formula (I) (or formula (I-1), formula (I-2), formula (I-3), formula (I-4), formula (I-5), formula (II-1), formula (II-2), formula (II-3), formula (II-4) or formula (I ') as described in the present disclosure as an active ingredient or a pharmaceutically acceptable salt thereof may be prepared into a suitable formulation form according to a suitable administration route including, but not limited to, nasal administration, inhalation administration, topical administration, oral mucosal administration, rectal administration, pleural cavity administration, peritoneal administration, vaginal administration, intramuscular administration, subcutaneous administration, transdermal administration, epidural cavity administration, intrathecal administration and intravenous administration, such as spray formulations, patches, tablets (e.g., conventional tablets, dispersible tablets, orally disintegrating tablets), capsules (e.g., soft, hard, enteric-coated capsules), dragees, lozenges, powders, granules, powder injection, suppositories, or liquid formulations (e.g., suspensions (e.g., aqueous or oily), solutions, emulsions, or syrups), or conventional injectable forms such as injectable solutions (e.g., sterile injectable solutions formulated with water, ringer's solution, or isotonic sodium chloride solution, etc. as a carrier or solvent according to methods known in the art) or lyophilized compositions. The person skilled in the art can also prepare the compounds of formula (I) as desired in conventional, dispersible, chewable, orally fast disintegrating or fast dissolving formulations, or in slow-release or controlled-release capsules.

The compound of formula (I) (or formula (I-1), formula (I-2), formula (I-3), formula (I-4), formula (I-5), formula (II-1), formula (II-2), formula (II-3), formula (II-4) or formula (I') as described herein as an active ingredient) is contained in a pharmaceutically acceptable carrier or diluent in an amount sufficient to deliver to a subject a therapeutically effective amount for the indication in need of treatment without causing serious toxic effects in the subject being treated. The dosage of active compound for all diseases or conditions mentioned herein is, for example, about 5ng/kg subject body weight/day to 500mg/kg subject body weight/day, about 1 ng/kg subject body weight/day to 300mg/kg subject body weight/day, for example, 0.1 to 100mg/kg subject body weight/day, or 0.5 to about 25mg/kg subject body weight/day.

The compounds of formula (I) (or formula (I-1), formula (I-2), formula (I-3), formula (I-4), formula (I-5), formula (II-1), formula (II-2), formula (II-3), formula (II-4) or formula (I') described herein, or pharmaceutically acceptable salts thereof, may conveniently be administered in any suitable formulation format, including, but not limited to, containing less than 1mg,1mg to 3000mg,5mg to 1000mg, e.g., 5 to 500mg,25 to 250mg of active ingredient per unit dosage form. IV kit/packaging article

The compounds of formula (I) (or compounds of formula (I-1), formula (I-2), formula (I-3), formula (I-4), formula (I-5), formula (II-1), formula (II-2), formula (II-3), formula (II-4), or formula (I'), or pharmaceutically acceptable salts, solvates, isotopically enriched analogs, polymorphs, stereoisomers (including enantiomers), or mixtures of stereoisomers thereof, described herein, are useful as pharmaceutical agents. The pharmaceutical agents of the present disclosure or the pharmaceutical compositions of the present disclosure may be present in a kit/packaging article. The kit/packaging article may comprise a package or container. The package or container includes, but is not limited to, an ampoule (ampoule), a blister pack, a pharmaceutical plastic bottle, a vial, a pharmaceutical glass bottle, a container, a syringe, a laminated flexible package, a co-extruded film infusion container, a test tube, a dispensing device, and the like. The kit/packaging article may contain instructions for use of the product. V. methods of treatment and uses

The compounds of formula (I) (or compounds of formula (I-1), formula (I-2), formula (I-3), formula (I-4), formula (I-5), formula (II-1), formula (II-2), formula (II-3), formula (II-4), or formula (I'), or pharmaceutically acceptable salts, solvates, isotopically enriched analogs, polymorphs, stereoisomers (including enantiomers), or mixtures of stereoisomers thereof, described in this disclosure, may also be used as a medicament. In particular, the compounds of formula (I) (or formula (I-1), formula (I-2), formula (I-3), formula (I-4), formula (I-5), formula (II-1), formula (II-2), formula (II-3), formula (II-4) or formula (I'), or pharmaceutically acceptable salts, solvates, isotopically enriched analogs, polymorphs, stereoisomers (including enantiomers), or mixtures of stereoisomers thereof, described herein, may be used in the manufacture of a medicament for the prevention and/or treatment of a disease or disorder associated with a cereblon protein.

The disease or condition associated with the cereblon protein is selected from the group consisting of a tumor, an infectious disease, an inflammatory disease, an autoimmune disease, anemia, hemorrhagic shock, transplant rejection, multiple Organ Dysfunction Syndrome (MODS), sarcoidosis, adult respiratory distress syndrome, cardiovascular disease, richter Syndrome (RS), acute liver failure, or diabetes.

The disease or condition associated with the cereblon protein is selected from the group consisting of myeloma, including multiple myeloma, plasma cell myeloma, smoldering multiple myeloma, myelofibrosis, myelopathy, myelodysplastic syndrome (MDS), myelodysplastic syndrome treated in the past, transplantation-related cancers, neutropenia, leukemia, including Acute Myelogenous Leukemia (AML), chronic Myelogenous Leukemia (CML), chronic myelogenous leukemia, acute Lymphoblastic Leukemia (ALL), chronic Lymphoblastic Leukemia (CLL), B-cell chronic lymphoblastic leukemia, chronic lymphocytic leukemia, Anemia associated with leukemia, acute B-lymphoblastic leukemia, T-lymphoblastic leukemia, acute T-lymphoblastic leukemia, lymphoma cell leukemia, monocytic leukemia, myelogenous monocytic leukemia, lymphomas including diffuse large B-cell lymphoma, non-Hodgkin's lymphoma, anaplastic large-cell lymphoma, CD20 positive lymphoma, mantle cell lymphoma, follicular Lymphoma (FL), burkitt's lymphoma, marginal Zone Lymphoma (MZL), primary lymphoma, B-cell lymphoma, recurrent B-cell non-Hodgkin's lymphoma, recurrent diffuse large B-cell lymphoma, Recurrent mediastinum (thymus) large B-cell lymphoma, primary mediastinum (thymus) large B-cell lymphoma, recurrent non-hodgkin lymphoma, refractory B-cell non-hodgkin lymphoma, refractory diffuse large B-cell lymphoma, refractory primary mediastinum (thymus) large B-cell lymphoma, refractory transformed non-hodgkin lymphoma, thyroid cancer, melanoma, lung cancer including lung adenocarcinoma, lung squamous carcinoma, non-small cell lung carcinoma, inflammatory myofibroblastic carcinoma, colorectal cancer, intestinal cancer, brain glioma, astrocytoma, ovarian cancer, bronchial carcinoma, prostate cancer, breast cancer including triple negative breast cancer, Sporadic breast cancer and cowden patients, pancreatic cancer, central nervous system cancer, neuroblastoma, glioma, peripheral neuroepithelial tumor, extramedullary plasmacytoma, gastric cancer, gastrointestinal stromal tumor, esophageal cancer, large intestine adenocarcinoma, esophageal squamous cell carcinoma, liver cancer, renal cell carcinoma, bladder cancer, endometrial cancer, uterine cancer, head and neck cancer, brain cancer, oral cancer, sarcomas including rhabdomyosarcoma, various adipose-derived tumors, ewing's sarcoma/primitive neuroectodermal tumor (Ewing/PNETs), and leiomyosarcoma, urothelial cancer, basal cell carcinoma, oral squamous cell carcinoma, cholangiocarcinoma, bone cancer, cervical cancer, skin cancer, richter Syndrome (RS), sepsis syndrome, autoimmune diseases including rheumatoid arthritis Autoimmune encephalomyelitis, ankylosing spondylitis, psoriasis, psoriatic arthritis, systemic lupus erythematosus, multiple sclerosis, recurrent oral ulcer, kawasaki disease, multiple myositis/dermatomyositis, sjogren's syndrome, atopic dermatitis, suppurative sweat gland, gout, type I diabetes, urticaria, inflammatory bowel disease (including Crohn's disease and ulcerative colitis), keratoconjunctival xerosis, inflammatory diseases (including Crohn's disease and ulcerative colitis, pneumonia, osteoarthritis, synovitis, systemic inflammatory reaction syndrome, airway inflammation, bronchitis, cerebral malaria, infectious diseases (including viral pneumonia, AIDS), inflammatory diseases (AIDS), COVID-19 novel coronavirus infection, gram-negative bacterial infection, gram-positive bacterial infection, tuberculosis, etc., infectious shock, tuberculosis, bacterial meningitis, chronic obstructive pulmonary disease, asthma, hemorrhagic shock, organ (including kidney, heart, lung) or tissue graft rejection, diabetes, sarcoidosis, adult respiratory distress syndrome, anemia, infantile aplastic anemia, cardiovascular diseases (e.g., coronary heart disease, congestive heart failure, myocardial infarction, atherosclerosis), multiple organ failure due to cachexia and septic shock, or acute liver failure.

The present disclosure provides methods for preventing and/or treating a disease or disorder associated with cereblon protein in a subject, comprising administering to the subject a therapeutically effective amount of a compound of formula (I) (or formula (I-1), formula (I-2), formula (I-3), formula (I-4), formula (I-5), formula (II-1), formula (II-2), formula (II-3), formula (II-4), or formula (I '), or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of the present disclosure comprising a compound of formula (I) (or formula (I-1), formula (I-2), formula (I-3), formula (I-4), formula (I-5), formula (II-1), formula (II-2), formula (II-3), formula (II-4), or formula (I'), or a pharmaceutically acceptable salt thereof, as an active ingredient.

In a method for preventing and/or treating a disease or disorder associated with the cereblon protein, a therapeutically effective amount of a compound of formula (I) (or formula (I-1), formula (I-2), formula (I-3), formula (I-4), formula (I-5), formula (II-2), formula (II-3), or formula (I ') described in the present disclosure is administered to the subject by at least one mode of administration selected from nasal administration, inhalation administration, topical administration, oral mucosal administration, rectal administration, pleural cavity administration, peritoneal administration, intramuscular administration, subcutaneous administration, transdermal administration, epidural cavity administration, intrathecal administration, and intravenous administration of a compound of formula (I) (or formula (I-1), formula (I-2), formula (I-3), formula (II-4), or formula (I') described in the present disclosure.

The term "treatment" or "treatment" refers to administering to a subject a pharmaceutical composition of a compound of formula (I) (or formula (I-1), formula (I-2), formula (I-3), formula (I-4), formula (I-5), formula (II-1), formula (II-2), formula (II-3), formula (II-4) or formula (I ') or a pharmaceutically acceptable salt thereof, or a compound of formula (I) (or formula (I-1), formula (I-2), formula (I-3), formula (I-4), formula (I-5), formula (II-1), formula (II-2), formula (II-3), formula (II-4) or formula (I') or a pharmaceutically acceptable salt thereof) as described herein to slow down (alleviate) the progression of an undesired disease or disorder (e.g., tumor). Beneficial or desired clinical results of the present disclosure include, but are not limited to, alleviation of symptoms, diminishment of severity of disease, stabilization of disease state, delay or slowing of disease progression, amelioration or palliation of the disease, and remission of the disease.

The "therapeutically effective amount" of a compound of the present disclosure depends on a variety of factors including the activity of the particular compound being used, the metabolic stability and length of action of that compound, the age, sex, and weight of the patient, the general medical condition of the patient, the mode and time of administration, the rate of excretion, drug combination, and the disease or condition of the patient being treated. One skilled in the art will be able to determine the appropriate dosage based on these and other factors.

It will be appreciated that the choice of the active compound(s) and/or composition(s) and the dosage thereof will depend on the individual base case (the individual case should generally be optimized). The administration and dosing regimen should be within the ability of those skilled in the art, and the appropriate dosage will depend on many factors including the level of knowledge of the ordinarily skilled physician, veterinarian or researcher (see, e.g., lijun monograph, "clinical pharmacology", 4 th edition, human health Press (2008)).

The patient or subject treated as described above refers to an animal, such as a mammal, including but not limited to a primate (e.g., human), cow, sheep, goat, horse, dog, cat, rabbit, guinea pig, rat, mouse, etc. VI preparation method

The present disclosure also provides a process for preparing a compound of formula (I), comprising using a compound of formula (M1) and a compound of formula (M2) as starting materials to prepare a compound of formula (I): Wherein R _a1、R_a2、R_a3、R_a4、(R_a5)_m, Z, R, ring B, ring C, (R _d2)_n2、(R_d3)_n3), and m1 are as defined in the disclosure of compounds of formula (I) and sub-embodiments thereof, and R _w3 represents CHO, COOH or Wherein R _c2 is as defined in the formula (I) and sub-embodiments thereof of the present disclosure and the group LE represents Cl, br, I, OMs, OTs, or ONs, wherein (1) -R _w1-R_w2 representAnd R representsOr (2) -R _w1-R_w2 representsAnd R representsOr (3) -R _w1-R_w2 represents-NH-NH ₂ and R represents-NH-, or (4) -R _w1-R_w2 representsAnd R representsWherein R _w, ring A ₁、(R_d1)_n1, ring A ₂ and R _d4)_n4 are as defined in the compounds of formula (I) of the present disclosure and in their sub-embodiments, wherein R _c3 and R _c4 represent H when R _w3 represents CHO, or R _c3 and R _c4 together form a carbonyl group when R _w3 represents COOH, or R _w3 representsWhen R _c3 represents H, and R _c4 is R _c2.

In some embodiments of the methods of preparing a compound of formula (I) of the present disclosure, when R _w3 represents CHO, the compound of formula (M1) is subjected to a reductive amination reaction with a compound of formula (M2) to prepare a compound of formula (I), wherein R _c3 and R _c4 in the compound of formula (I) represent H.

In some embodiments of the methods of preparing the compounds of formula (I) of the present disclosure, the reductive amination reaction may be performed in the presence of sodium borohydride acetate and an organic solvent (e.g., 1, 2-dichloroethane, N-dimethylformamide, or dichloromethane) at room temperature to 80 ℃ (e.g., 40 ℃ -60 ℃, 40 ℃ -50 ℃, or 50 ℃ -60 ℃). Alternatively, the reductive amination reaction may be carried out in the presence of sodium borohydride, 1, 4-dioxane at room temperature to 80 ℃ (e.g., 40 ℃ -60 ℃, 40 ℃ -50 ℃, or 50 ℃ -60 ℃). In some embodiments, the molar ratio of the compound of formula (M1) to the compound of formula (M2) may be, for example, 1.0 to 2:1,1:1.0 to 2,1:1.1 to 1.5,1:1.1 to 1.2, or 1:1.2 to 1.3, etc.

In some embodiments of the methods of preparing compounds of formula (I) of the present disclosure, when R _w3 represents COOH, the compounds of formula (M1) undergo an amide condensation reaction with compounds of formula (M2) to prepare compounds of formula (I), wherein R _c3 and R _c4 in the compounds of formula (I) together form a carbonyl group.

In some embodiments of the methods of preparing compounds of formula (I) of the present disclosure, the amide condensation reaction may be performed, for example, in the presence of HATU/DIEA/DMF, or HATU/TEA/DMF, or HOAt/EDCI/TEA/DCM, at room temperature. In some embodiments, the molar ratio of the compound of formula (M1) to the compound of formula (M2) may be, for example, 1.0 to 2:1,1:1.0 to 2,1:1.1 to 1.5,1:1.1 to 1.2, or 1:1.2 to 1.3, etc.

In some embodiments of the methods of preparing compounds of formula (I) of the present disclosure, when R _w3 representsIn the process, the compound of formula (M1) and the compound of formula (M2) undergo an amine alkylation reaction to prepare the compound of formula (I), wherein R _c3 in the compound of formula (I) represents H, and R _c4 is R _c2.

In some embodiments of the methods of preparing compounds of formula (I) of the present disclosure, the amine alkylation reaction may be performed, for example, in the presence of DIEA and sodium iodide, or triethylamine and sodium iodide, at room temperature to 80 ℃ (e.g., 40 ℃ -60 ℃, 40 ℃ -50 ℃, or 50 ℃ -60 ℃). In some embodiments, the molar ratio of the compound of formula (M1) to the compound of formula (M2) may be, for example, 1.0 to 2:1,1:1.0 to 2,1:1.1 to 1.5,1:1.1 to 1.2, or 1:1.2 to 1.3, etc.

In some embodiments of the methods of preparing compounds of formula (I) of the present disclosure, when-R _w1-R_w2 of the compound of formula (M1) representsIn the case where the compound of formula (M1) is prepared by reacting a compound of formula (M3) with a compound of formula (M4) as a starting material,Y represents F or Br, W ₁ represents H and W ₂ represents an amino protecting group, or W ₁ represents an amino protecting group and W ₂ represents H.

In some embodiments of the methods of preparing compounds of formula (I) of the present disclosure, when Y represents F, the compounds of formula (M3) and (M4) are prepared by palladium catalyzed coupling reactions to give compounds of formula (M1). In some embodiments of the methods of preparing compounds of formula (I) of the present disclosure, palladium catalyzed coupling reactions may be performed in the presence of cesium carbonate, a palladium catalyst, and N, N-dimethylformamide, for example, at 50 ℃ to 100 ℃ (e.g., 80 ℃).

In some embodiments of the methods of preparing compounds of formula (I) of the present disclosure, when Y represents Br, compounds of formula (M3) are prepared with compounds of formula (M4) by a substitution reaction to produce compounds of formula (M1). In some embodiments of the methods of preparing compounds of formula (I) of the present disclosure, the substitution reaction may be performed in the presence of N, N-diisopropylethylamine and dimethyl sulfoxide under conditions of, for example, 80 ℃ to 150 ℃ (e.g., 130 ℃).

In some embodiments of the methods of preparing compounds of formula (I) of the present disclosure, the amino protecting group may be, for example, boc, and the like. Removal of the protecting group may be accomplished by techniques and methods well known to those skilled in the art, for example, removal of the protecting group Boc may be accomplished under acidic conditions, such as hydrochloric acid, or trifluoroacetic acid. VII definition of

The following words, phrases and symbols used in the present specification have the meanings as described below in general unless otherwise indicated.

Generally, the nomenclature used herein (including IUPAC nomenclature) and the laboratory procedures described below (including those used in cell culture, organic chemistry, analytical chemistry, pharmacology, and the like) are those well known and commonly employed in the art. Unless defined otherwise, all scientific and technical terms used herein in connection with the disclosure described herein have the same meaning as commonly understood by one of ordinary skill in the art. In addition, in the claims and/or the specification, the terms "a" or "an" when used in conjunction with the term "comprising" or noun may have the meaning of "one" but are also consistent with the meaning of "one or more", "at least one", and "one or more". Similarly, the term "another" or "other" may mean at least a second or more.

It will be understood that whenever aspects are described herein by the terms "comprising" or "including," other similar aspects are also provided as described by "consisting of and/or" consisting essentially of.

The term "about" alone or in combination is used herein to mean approximately, about, or about. When the term "about" is used in conjunction with a numerical range, it modifies that range by extending the boundaries above and below the numerical values set forth. In general, the term "about" can modify a value above and below the stated value by changing, for example, 10%, 5%, 2%, or 1% up or down (up or down).

In this context, the term "a" is used herein, singly or in combination the term "....the term means a key". Meaning that it is a bond linkage (i.e., meaning that it is absent). For example, the term "R _c represents a bond" means that R _c is a bond linker. In other words, when R _c is a bond, the ring B group of the structure of formula (I) is directly attached to ring A in the structure of formula (I).

The term "optional substitution" ("optionally substitutedwith") used herein, alone or in combination, means that the indicated group may be unsubstituted or substituted with one or more substituents as defined herein. In this context, the term "a" is used herein, the terms "optionally substituted" and "unsubstituted or substituted" may be used interchangeably. The term "substituted" generally means that one or more hydrogens in the structure referred to are replaced with a specific substituent, either the same or different. The number of substituents is in principle not subject to any restrictions, or is automatically limited by the size of the building unit (i.e. the total number of hydrogen atoms that can be replaced of the building unit), or is as defined explicitly herein.

In this context, the bond broken by the wavy line shows the point of attachment of the depicted group to the rest of the molecule. For example, monovalent groups are depicted belowR _c representing said group is linked to R of the structure of formula (I).

The term "one or more" used herein, alone or in combination, in the term "substituted with one or more substituents selected from the group consisting of..once again..may mean that part or all of the hydrogen of the group in question is replaced with a substituent, the number of substituents including, but not limited to, 1 to 40, such as 1 to 30, such as 1 to 25, 1 to 20, 1 to 15, 1 to 10, 1 to 5,1 to 4, 1 to 3, 1 to 2 or 1. This number is in principle not subject to any restrictions or is automatically limited by the size of the building block, for example when the radicals mentioned are methyl, the number of substituents may be from 1 to 3.

The term "deuterated" used herein, alone or in combination, means that one or more hydrogens of the mentioned groups are replaced with deuterium atoms.

The term "oxo" or "oxo" used herein, alone or in combination, refers to = O.

The term "carbonyl" used herein, alone or in combination, refers to C (O) or C (=o).

The term "halogen atom" or "halogen" as used herein, alone or in combination, refers to fluorine, chlorine, bromine or iodine.

The term "alkyl" as used herein, alone or in combination, refers to a straight or branched chain alkyl group. The term "C _x-C_y alkyl" or "C _x-y alkyl" (x and y are each integers) refers to straight or branched chain alkyl groups containing from x to y carbon atoms. The term "C ₁-C₁₀ alkyl" as used herein, alone or in combination, refers to a straight or branched chain alkyl group containing from 1 to 10 carbon atoms. Examples of the term "C ₁-C₁₀ alkyl" include C _1-9 alkyl, C _1-8 alkyl, C _2-8 alkyl, C _1-7 alkyl, C _1-6 alkyl, C _1-5 alkyl, C _1-4 alkyl, C ₁-C₃ alkyl, and C ₁-C₂ alkyl. Representative examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, tert-pentyl, and hexyl. The term "C _1-3 alkyl" or "C ₁-C₃ alkyl" of the present disclosure refers to an alkyl group containing 1 to 3 carbon atoms, representative examples of which include methyl, ethyl, n-propyl, and isopropyl. In the present disclosure, the "alkyl" is optionally substituted, and the substituents are optionally one or more (e.g., 1-10, 1-6, 1-5, 1-4, or 1-3) groups each independently selected from, for example, halogen, hydroxy, cyano, C _1-3 alkyl, C _1-3 alkoxy, halogenated C _1-6 alkoxy, Substituents that are halo-C _1-6 alkyl (e.g., trifluoromethyl), C _3-6 cycloalkyl, 4-to 7-membered heterocyclyl, or combinations thereof.

The term "haloalkyl" as used herein, alone or in combination, refers to a straight or branched chain alkyl group substituted with one or more halogens wherein one or more hydrogens in the alkyl group are replaced with a halogen. The term "halo-C _x-C_y alkyl" or "halo-C _x-y alkyl" (x and y are each integers) refers to straight or branched chain alkyl groups containing from x to y carbon atoms substituted with one or more halogens. The term "halo C _1-10 alkyl" used in this disclosure, alone or in combination, refers to a straight or branched chain alkyl group containing 1 to 10 carbon atoms substituted with one or more halogens. Examples of halogenated C _{1- 10} alkyl groups of the present disclosure include halogenated C _1-9 alkyl groups, such as halogenated C _1-8 alkyl groups, halogenated C _2-8 alkyl groups, halogenated C _1-7 alkyl groups, halogenated C _1-6 alkyl groups, halogenated C _1-5 alkyl groups, or halogenated C _1-4 alkyl groups. Representative examples include halomethyl, haloethyl, halon-propyl, haloisopropyl, halon-butyl, haloisobutyl, halosec-butyl, halotert-butyl, halopentyl, haloisopentyl, haloneopentyl, haloterpentyl, halohexyl, haloheptyl, halooctyl, halononyl, and halodecyl. The term "halogenated C _1-3 alkyl" or "halogenated C ₁-C₃ alkyl" in the present disclosure refers to an alkyl group containing 1 to 3 carbon atoms substituted with one or more halogens, representative examples of which include halomethyl (e.g., trifluoromethyl), haloethyl, halo-n-propyl, and halo-isopropyl.

The term "deuterated alkyl" as used herein, alone or in combination, refers to a straight or branched chain alkyl group substituted with one or more deuterium atoms wherein one or more hydrogens in the alkyl group are replaced with a deuterium atom. The term "deuterated C _x-C_y alkyl" or "deuterated C _x-y alkyl" (x and y are each integers) refers to a straight or branched chain alkyl group containing from x to y carbon atoms substituted with one or more deuterium atoms. The term "deuterated C _1-10 alkyl" used in this disclosure, alone or in combination, refers to a straight or branched chain alkyl group containing 1 to 10 carbon atoms substituted with one or more deuterium atoms. examples of deuterated C _1-10 alkyl of the present disclosure include deuterated C _1-9 alkyl, such as deuterated C _1-8 alkyl, deuterated C _2-8 alkyl, deuterated C _1-7 alkyl, deuterated C _1-6 alkyl, deuterated C _1-5 alkyl, or deuterated C _1-4 alkyl. Representative examples include perdeuterated methyl (CD ₃), perdeuterated ethyl (CD ₃CD₂), perdeuterated n-propyl, perdeuterated isopropyl, perdeuterated n-butyl, perdeuterated isobutyl, perdeuterated sec-butyl, perdeuterated tert-butyl, perdeuterated pentyl, perdeuterated isopentyl, perdeuterated neopentyl, perdeuterated tert-pentyl, and perdeuterated hexyl. The term "deuterated C _1-3 alkyl" or "deuterated C ₁-C₃ alkyl" in the present disclosure refers to an alkyl group containing 1 to 3 carbon atoms substituted with one or more deuterium atoms, representative examples of which include perdeuterated methyl (CD ₃ -) and perdeuterated ethyl (CD ₃CD₂).

The term "alkoxy", as used herein, alone or in combination, refers to a straight or branched chain alkoxy group having the structural formula alkyl-O-. Alternatively, the alkyl portion of the alkoxy group may contain 1 to 10 (e.g., 1 to 6, 1 to 4, or 1 to 3) carbon atoms. Representative examples of "alkoxy" include, but are not limited to, methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, pentyloxy, 2-pentyloxy, isopentyloxy, neopentyloxy, hexyloxy, 2-hexyloxy, 3-methylpentyloxy, and the like. The term "C ₁-C₆ alkoxy" or "C _1-3 alkoxy" refers to straight or branched chain alkoxy groups containing 1 to 6 carbon atoms. Representative examples of C _1-6 alkoxy groups include, but are not limited to, methoxy, ethoxy, n-propoxy, isopropoxy, butoxy, pentoxy, and hexoxy.

The term "haloalkoxy" as used herein, alone or in combination, refers to an alkoxy group substituted with one or more halogens. Alternatively, the alkyl portion of the alkoxy group may contain 1 to 10 (e.g., 1 to 6, 1 to 4, or 1 to 3) carbon atoms. Examples of "haloalkoxy" include halogenated C _1-6 alkoxy and halogenated C _1-4 alkoxy. Representative examples include, but are not limited to F₃C-O-、FCH₂-O-、F₂CH-O-、ClCH₂-O-、Cl₂CH-O-、CF₃CF₂-O-、CF₃CHF-O-、CHF₂CF₂-O-、CHF₂CHF-O-、CF₃CH₂-O- or CH ₂ClCH₂ -O-.

In the present invention, the term "heteroaryl", alone or in combination, refers to a 5-to 30-membered (optionally 5-to 20-membered, 5-to 15-membered, 5-to 12-membered, 5-to 11-membered, 5-to 10-membered, 5-to 9-membered, 5-to 8-membered, 5-to 7-membered, 5-to 6-membered, 6-to 15-membered, 6-to 9-membered, 6-to 10-membered, or 6-to 20-membered) monocyclic or bicyclic or polycyclic hydrocarbon group containing at least one aromatic ring having 1 or more (e.g., 1-6, or 1-to 5, or 1-to 4, or 1-to 3) heteroatoms independently selected from oxygen, nitrogen, and sulfur. Bicyclic or polycyclic heteroaryl groups include bicyclic, tricyclic, tetracyclic or polycyclic heteroaryl groups containing one ring that is an aromatic ring having one or more (e.g., 1-4, 1-3, 1-2 or 1) heteroatoms independently selected from O, S and N, and the other rings contained may be saturated, partially unsaturated or aromatic and may be carbocyclic or contain one or more (e.g., 1-4, 1-3, 1-2 or 1) heteroatoms independently selected from O, S and N. Examples of monocyclic heteroaryl groups include, but are not limited to, furyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, tetrazolyl, and triazinyl. Examples of bicyclic heteroaryl groups include, but are not limited to, indolyl, isoindolyl, isoindolinyl, benzofuranyl, isobenzofuranyl, benzothienyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazole, benzo [2,1,3] oxadiazolyl, benzo [2,1,3] thiadiazolyl, benzo [1,2,3] thiadiazolyl, quinolinyl, isoquinolinyl, naphthyridinyl, cinnolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, oxazolopyridinyl, furopyridinyl, pteridinyl, purinyl, pyridopyridinyl, pyrazolo [1,5-a ] pyridinyl, Pyrazolo [1,5-a ] pyrimidinyl, imidazo [1,2-a ] pyridinyl, 1H-pyrrolo [3,2-b ] pyridinyl, 1H-pyrrolo [2,3-b ] pyridinyl, pyrrolo [2,1-b ] thiazolyl, imidazo [2,1-b ] thiazolyl, chromanyl, and 6, 7-dihydrothieno [3,2-d ] pyrimidinyl. Examples of tricyclic or polycyclic heteroaryl groups include, but are not limited to, acridinyl, benzindolyl, carbazolyl, dibenzofuranyl, xanthenyl, 5,6,7, 8-tetrahydrobenzo [4,5] thieno [2,3-d ] pyrimidinyl, and 6, 7-dihydro-5H-cyclopenta [4,5] thieno [2,3-d ] pyrimidinyl. The heteroaryl group may be unsubstituted or substituted. Substituted heteroaryl means heteroaryl substituted one or more times (e.g., 1-4, 1-3, or 1-2) with a substituent optionally selected from, for example, deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, optionally deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, optionally deuterated C _3-6 cycloalkyl, Optionally deuterated C _1-6 alkoxy, halogenated C _1-6 alkoxy, optionally deuterated C _1-6 alkyl-NH-, NH ₂-C_1-6 alkylene, Optionally deuterated C _1-6 alkyl-NHC (O) -, optionally deuterated C _1-6 alkyl-C (O) NH-, C _2-6 alkynyl, C _2-6 alkenyl, or any combination thereof.

In the present invention, the term "heteroarylene", alone or in combination, refers to a divalent radical containing at least one 5-to 30-membered (optionally 5-to 20-membered, 5-to 15-membered, 5-to 12-membered, 5-to 11-membered, 5-to 10-membered, 5-to 9-membered, 5-to 8-membered, 5-to 7-membered, 5-to 6-membered, 6-to 15-membered, 6-to 9-membered, 6-to 10-membered, or 6-to 20-membered) mono-or bi-or polycyclic hydrocarbon having 1 or more (e.g., 1-6, or 1-to 5, or 1-to 4, or 1-to 3) heteroatoms independently selected from oxygen, nitrogen, and sulfur. Bicyclic or polycyclic heteroarylene includes bicyclic, tricyclic, tetracyclic or polycyclic heteroarylene groups containing one ring being an aromatic ring having one or more (e.g., 1-4, 1-3, 1-2 or 1) heteroatoms independently selected from O, S and N, and the other rings contained may be saturated, partially unsaturated or aromatic and may be carbocyclic or contain one or more (e.g., 1-4, 1-3, 1-2 or 1) heteroatoms independently selected from O, S and N. Examples of monocyclic heteroarylene groups include, but are not limited to, furanylene, oxazolylene, isoxazolylene, oxadiazolylene, thiophenylene, thiazolylene, isothiazolylene, thiadiazolylene, pyrrolylene, imidazolylene, pyrazolylene, triazolylene, pyridinyl, pyrimidinylene, pyridazinylene, pyrazinylene, tetrazolylene, and triazinylene. Examples of bicycloheteroarylene groups include, but are not limited to, indolylene, isoindolylene, isoindolinylene, benzofuranylene, isobenzofuranylene, benzothienyl, indazolyl, benzimidazolylene, benzoxazolyl, benzisoxazolyl, benzothiazolylene, benzisothiazolyl, benzotriazolylene, benzo [2,1,3] oxadiazolyl, benzo [2,1,3] thiadiazolyl, benzo [1,2,3] thiadiazolyl, quinolinylene, isoquinolinyl, naphthyridinyl, cinnolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, oxazolopyridinyl, furanopyridinyl, A pteridine group, a purinylene group, a pyrido-pyridinyl group, a pyrazolo [1,5-a ] pyrimidinyl group, an imidazo [1,2-a ] pyridinyl group, a 1H-pyrrolo [3,2-b ] pyridinyl group, a 1H-pyrrolo [2,3-b ] pyridinyl group, a pyrrolo [2,1-b ] thiazolyl group, an imidazo [2,1-b ] thiazolyl group, a chromanyl group, and a 6, 7-dihydrothieno [3,2-d ] pyrimidinyl group. Examples of tricyclic or polycyclic heteroarylene groups include, but are not limited to, acriylene, benzindolyene, carbazolylene, dibenzofuranylene, xanthylene, 5,6,7, 8-tetrahydrobenzo [4,5] thieno [2,3-d ] pyrimidine subunit, and 6, 7-dihydro-5H-cyclopenta [4,5] thieno [2,3-d ] pyrimidine subunit. The heteroarylene group may be unsubstituted or substituted. substituted heteroarylene means heteroarylene substituted one or more times (e.g., 1-4, 1-3, or 1-2) with a substituent optionally selected from, for example, deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, optionally deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, optionally deuterated C _3-6 cycloalkyl, Optionally deuterated C _1-6 alkoxy, halogenated C _1-6 alkoxy, optionally deuterated C _1-6 alkyl-NH-, NH ₂-C_1-6 alkylene, Optionally deuterated C _1-6 alkyl-NHC (O) -, optionally deuterated C _1-6 alkyl-C (O) NH-, C _2-6 alkynyl, C _2-6 alkenyl, or any combination thereof.

The term "aryl" as used herein, alone or in combination, refers to a monovalent aromatic hydrocarbon radical comprising 5 to 30 (e.g., 5-20,5-15, 5-12, 5-10, 5-9, 5-8, 5-7, 5-6, 6-15, 6-9, 6 to 10 membered, or 6-20) carbon atoms and optionally comprising one or more fused rings, such as phenyl or naphthyl or fluorenyl. In the present disclosure, the "aryl" is an optionally substituted aryl. Substituted aryl refers to aryl substituted one or more times (e.g., 1-4, 1-3, or 1-2 times) with a substituent, such as aryl is mono-, di-, tri-, or poly-substituted with a substituent optionally selected from, for example, deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, oxo, optionally deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, optionally deuterated C _3-6 cycloalkyl, optionally deuterated C _1-6 alkoxy, halogenated C _1-6 alkoxy, optionally deuterated C _1-6 alkyl-NH-, NH ₂-C_1-6 alkylene, optionally deuterated C _1-6 alkyl-NHC (O) -, optionally deuterated C _1-6 alkyl-C (O) NH-, C _2-6 alkynyl, C _2-6 alkenyl, or any combination thereof.

In the present disclosure, the term "arylene" used alone or in combination refers to a divalent aromatic hydrocarbon group comprising 5 to 30 (e.g., 5-20, 5-15, 5-12, 5-10, 5-9, 5-8, 5-7, 5-6, 6-15, 6-9, 6 to 10 members, or 6-20) carbon atoms and optionally comprising one or more fused rings, such as phenylene (e.g., phenylene) Or naphthylene or fluorenylene. In the present disclosure, the "arylene" is an optionally substituted arylene. Substituted arylene means arylene substituted one or more times (e.g., 1-4, 1-3, or 1-2) with a substituent such as arylene is mono-, di-, tri-, or poly-substituted with a substituent optionally selected from, for example, deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, oxo, optionally deuterated C _1-6 alkyl, halo C _1-6 alkyl, optionally deuterated C _3-6 cycloalkyl, optionally deuterated C _1-6 alkoxy, halo C _1-6 alkoxy, optionally deuterated C _1-6 alkyl-NH-, NH ₂-C_1-6 alkylene, optionally deuterated C _1-6 alkyl-NHC (O) -, optionally deuterated C _1-6 alkyl-C (O) NH-, C _2-6 alkynyl, C _2-6 alkenyl, or any combination thereof.

The term "cycloalkyl" as used herein, alone or in combination, refers to a saturated or partially unsaturated (i.e., having one or more double bonds, but not being fully conjugated) monocyclic or bicyclic or tricyclic or polycyclic cycloalkyl group containing a number of carbon atoms including, but not limited to, 3 to 30 carbon atoms (i.e., C _3-30 cycloalkyl), 3 to 25 carbon atoms (i.e., C _3-25 cycloalkyl), 3 to 20 carbon atoms (i.e., C _3-20 cycloalkyl), 3 to 15 carbon atoms (i.e., C _3-15 cycloalkyl), 3 to 12 carbon atoms (i.e., C _3-12 cycloalkyl), 3 to 11 carbon atoms (i.e., C _3-11 cycloalkyl), 3 to 10 carbon atoms (i.e., C _3-10 cycloalkyl), 3 to 8 carbon atoms (i.e., C _3-8 cycloalkyl), 3 to 7 carbon atoms (i.e., C _3-7 cycloalkyl), 3 to 6 carbon atoms (i.e., C _3-6 cycloalkyl), 4 to 20 carbon atoms (i.e., C _4-20 cycloalkyl), 4 to 15 carbon atoms (i.e., C _4-15 cycloalkyl), 4 to 12 carbon atoms (i.e., C _4-12), and 4 to 10 carbon atoms (i.e., C _4-10 cycloalkyl). The term "cycloalkyl" includes monocyclic, bicyclic, tricyclic and polycyclic cycloalkyl groups having 3 to 30 carbon atoms. Examples of the term "cycloalkyl" include, but are not limited to, monocyclic cycloalkyl, bridged cycloalkyl (e.g., C _5-30 bridged cycloalkyl, C _5-20 bridged cycloalkyl, C _5-15 bridged cycloalkyl, and C _7-15 bridged cycloalkyl), bridged cycloalkyl, Condensed ring alkyl groups (e.g., C _5-30 condensed ring alkyl, C _5-20 condensed ring alkyl, C _5-15 condensed ring alkyl, C _6-30 condensed ring alkyl), C _6-20 fused ring alkyl, C _6-15 fused ring alkyl, C _7-30 fused ring alkyl, C _7-20 fused ring alkyl, C _7-15 -and C _8-15 -fused-ring alkyl) and spirocycloalkyl (e.g., C _{5- 30} spirocycloalkyl, C _5-20 spirocycloalkyl, C _5-15 spirocycloalkyl, C _6-30 spirocycloalkyl, C _6-20 spirocycloalkyl, C _6-15 spirocycloalkyl, C _7-30 spirocycloalkyl, C _7-20 spirocycloalkyl, C _7-15 spirocycloalkyl and C _8-15 spirocycloalkyl). Representative examples of monocyclic cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, and cyclooctyl. Examples of fused ring alkyl, spirocycloalkyl, and bridged cycloalkyl groups include, but are not limited to, decahydronaphthyl, octahydropentalenyl, octahydro-1H-indenyl, C _5-20 spirocycloalkyl, C _5-15 spirocycloalkyl, adamantyl, noradamantyl, bornyl, and norbornyl (IUPAC system is designated bicyclo [2.2.1] heptanyl). Herein, the "cycloalkyl" is optionally mono-or poly-substituted, such as, but not limited to, 2-,2,3-,2,4-,2,5-, or 2, 6-disubstituted cyclohexyl. The substituent of the substituted "cycloalkyl" is optionally one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1) substituents each independently selected from, for example, deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, oxo, optionally deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, optionally deuterated C _3-6 cycloalkyl, Optionally deuterated C _1-6 alkoxy, halogenated C _1-6 alkoxy, optionally deuterated C _1-6 alkyl-NH-, NH ₂-C_1-6 alkylene, Substituents that are optionally deuterated C _1-6 alkyl-NHC (O) -, optionally deuterated C _1-6 alkyl-C (O) NH-, C _2-6 alkynyl, C _2-6 alkenyl, or any combination thereof. Examples of the term "C _3-6 cycloalkyl" include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, and cyclohexyl.

The term "C _x-y spirocycloalkyl" (x and y are each integers), as used herein, alone or in combination, refers to a spirocycloalkyl group containing from x to y carbon atoms. The term "C _5-30 spirocycloalkyl" as used herein, alone or in combination, refers to spirocycloalkyl groups containing 5 to 30 (e.g., without limitation, 5-20,5-15,7-20,7-15,5-11,5-10, and 7-9) carbon atoms. The term "C _5-30 spirocyclic group" includes "C _5-20 spirocyclic group", "C _5-15 spirocyclic group", "C _7-15 spirocyclic group" and "C _7-20 spirocyclic group", representative examples of which include, but are not limited to, spiro [3.3] heptyl, Spiro [2.5] octyl, spiro [3.5] nonyl, spiro [3.5] nonenyl, spiro [4.4] nonyl, spiro [4.5] decyl, spiro [4.5] decenyl and spiro [5.5] undecyl. The "C _5-30 spirocycloalkyl" is optionally further substituted with a moiety selected from, for example, deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, oxo, optionally deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, optionally deuterated C _3-6 cycloalkyl, Optionally deuterated C _1-6 alkoxy, halogenated C _1-6 alkoxy, optionally deuterated C _1-6 alkyl-NH-, NH ₂-C_1-6 alkylene, One or more (e.g., 1-10) substituents of optionally deuterated C _1-6 alkyl-NHC (O) -, optionally deuterated C _1-6 alkyl-C (O) NH-, C _2-6 alkynyl, C _2-6 alkenyl, or any combination thereof, 1-6, 1-5, 1-4, or 1-3).

The term "C _x-y bridged cycloalkyl" (x and y are each integers), as used herein, alone or in combination, refers to bridged cycloalkyl groups containing from x to y carbon atoms. The term "C _5-30 bridged cycloalkyl", as used herein, alone or in combination, refers to bridged cycloalkyl groups containing 5 to 30 (e.g., without limitation, 5-20,6-20,7-20,5-15,7-15,5-11,5-10, and 7-9) carbon atoms. The term "C _5-30 bridged cycloalkyl" includes "C ₅-C₂₀ bridged group", "C ₆-C₂₀ bridged group", "C ₇-C₂₀ bridged group", and combinations thereof, Representative examples of "C _5-15 bridged cycloalkyl" and "C ₇-C₁₅ bridged cycloalkyl" include, but are not limited to, adamantyl (amadantanyl), noradamantyl, bornyl, norbornyl (systematic name bicyclo [2.2.1] heptanyl), 2-oxo-bicyclo [2.2.1] heptanyl, bicyclo [2.2.1] heptenyl, and cubanyl (cubanyl). The "C _5-30 bridged cycloalkyl" is optionally substituted with 1 to 10 (e.g., 1-6, 1-5, 1-4, or 1-3) substituents each independently selected from deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, oxo, optionally deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, Optionally deuterated C _3-6 cycloalkyl, optionally deuterated C _1-6 alkoxy, halogenated C _1-6 alkoxy, optionally deuterated C _1-6 alkyl-NH- NH ₂-C_1-6 alkylene, optionally deuterated C _1-6 alkyl-NHC (O) -, optionally deuterated C _1-6 alkyl-C (O) NH-, C _2-6 alkynyl, C _2-6 alkenyl, or any combination thereof.

The term "cycloalkylene", as used herein, alone or in combination, refers to a monocyclic or bicyclic or tricyclic or polycyclic hydrocarbon divalent radical of saturated and partially unsaturated (i.e., having one or more double bonds, but not being fully conjugated) containing a number of carbon atoms including, but not limited to, 3 to 30 carbon atoms (i.e., C _3-30 cycloalkylene), 3 to 25 carbon atoms (i.e., C _3-25 cycloalkylene), 3 to 20 carbon atoms (i.e., C _{3- 20} cycloalkylene), 3 to 15 carbon atoms (i.e., C _3-15 cycloalkylene), 3 to 12 carbon atoms (i.e., C _3-12 cycloalkylene), 3 to 11 carbon atoms (i.e., C _3-11 cycloalkylene), 3 to 10 carbon atoms (i.e., C _3-10 cycloalkylene), 3 to 8 carbon atoms (i.e., C _3-8 cycloalkylene), 3 to 7 carbon atoms (i.e., C _3-7 cycloalkylene), 3 to 6 carbon atoms (i.e., C _3-6 cycloalkylene), 4 to 20 carbon atoms (i.e., C _4-20 cycloalkylene), 4 to 15 carbon atoms (i.e., C _4-15 cycloalkylene), 4 to 38 carbon atoms (i.e., C _4-10). The term "cycloalkylene" includes mono-, bi-, tri-and polycyclic hydrocarbon divalent radicals having 3 to 30 carbon atoms. Examples of the term "cycloalkylene" include, but are not limited to, monocyclic cycloalkylene, bridged cycloalkyl (e.g., C _5-30 bridged cycloalkyl, C _5-20 bridged cycloalkyl, C _5-15 bridged cycloalkyl and C _7-15 bridged cycloalkyl), bridged cycloalkyl, A condensed ring alkylene group (e.g., a C _5-30 condensed ring alkylene group, a C _5-20 condensed ring alkylene group) C _5-15 alkylene group, C _6-30 alkylene group, and condensed ring alkyl group, C _6-20 Cycloalkylene, C _6-15 Cycloalkylene, C _{7- 30} Cycloalkylene, C _7-20 Cycloalkylene, C _7-15 Cycloalkylene and C _8-15 Cycloalkylene) and spiroalkylene (e.g., C _5-30 spiroalkylene, C _5-20 spiroalkylene, C _5-15 spirocyclic alkylene, C _6-30 spirocyclic alkylene, C _6-20 spirocyclic alkylene, C _6-15 spirocyclic alkylene, C _7-30 spiroalkylene, C _7-20 spiroalkylene, C _7-15 spiroalkylene and C _8-15 spiroalkylene). Representative examples of monocyclic cycloalkylene include, but are not limited to, cyclopropylene, cyclobutylene, cyclopentylene, cyclohexylene, cyclohexenylene, cycloheptylene, and cyclooctylene. Examples of the alkylene group, the spiroalkylene group and the bridged cycloalkyl group include, but are not limited to, decahydronaphthalene group, octahydropentalene group, octahydro-1H-indenylene group, 2, 3-dihydro-1H-indenylene group, C _5-20 spiroylene group (e.g., C _5-15 spiroylene group), adamantylene group, noradamantylene group and norbornylene group (IUPAC system is named bicyclo [2.2.1] heptane subunit). in the present disclosure, the "cycloalkylene" is optionally mono-or poly-substituted, such as, but not limited to, 2-,2,3-,2,4-,2,5-, or 2, 6-disubstituted cyclohexylene. The substituent of the substituted "cycloalkylene" is optionally one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1) substituents each independently selected from deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, oxo, optionally deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, optionally deuterated C _3-6 cycloalkyl, Optionally deuterated C _1-6 alkoxy, halogenated C _1-6 alkoxy, optionally deuterated C _1-6 alkyl-NH-, NH ₂-C_1-6 alkylene, Substituents that are optionally deuterated C _1-6 alkyl-NHC (O) -, optionally deuterated C _1-6 alkyl-C (O) NH-, C _2-6 alkynyl, C _2-6 alkenyl, or any combination thereof.

The term "C _x-y spiroalkylene" or "C _x-y spiroalkylene" (x and y are each integers) used herein, alone or in combination, refers to spiroalkylene groups containing from x to y carbon atoms. The term "C _5-30 spirocycloalkyl" as used herein, alone or in combination, refers to spirocycloalkyl groups containing from 5 to 30 (e.g., 5-20,5-15,7-20,7-15,5-11,5-10, 7-9) carbon atoms. The term "C _5-30 spirocycloalkyl" includes "C _5-20 spirocycloalkyl", "C _5-15 spirocycloalkyl", "C _7-15 spirocycloalkyl" and "C _7-20 spirocycloalkyl", representative examples of which include, but are not limited to, spiro [3.3] heptane subunit, spiro [2.5] octanediow, spiro [3.5] nonane subunit, spiro [3.5] nonene subunit, spiro [4.4] nonane subunit, spiro [4.5] decane subunit, spiro [4.5] decene subunit, and spiro [5.5] undecane subunit. the "C _5-30 spirocycloalkyl" is optionally further substituted with one or more (e.g., 1-10, 1-6, 1-5, 1-4, or 1-3) groups each independently selected from deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, oxo, optionally deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, Optionally deuterated C _3-6 cycloalkyl, optionally deuterated C _1-6 alkoxy, halogenated C _1-6 alkoxy, optionally deuterated C _1-6 alkyl-NH- NH ₂-C_1-6 alkylene, optionally deuterated C _1-6 alkyl-NHC (O) -, optionally deuterated C _1-6 alkyl-C (O) NH-, C _2-6 alkynyl, C _2-6 alkenyl or any combination thereof.

The term "C _x-y bridged cycloalkyl" or "C _x-y bridged cyclyl" (x and y are each integers) as used herein, alone or in combination, refers to bridged cycloalkyl groups containing from x to y carbon atoms. The term "C _5-30 bridged cycloalkyl" as used herein, alone or in combination, refers to bridged cycloalkyl groups containing 5 to 30 (e.g., without limitation, 5-20,6-20,7-20,5-15,7-15,5-11,5-10, and 7-9) carbon atoms. the term "C _5-30 bridged cycloalkyl" includes "C _5-20 bridged cycloalkyl", "C _6-20 bridged cycloalkyl", "C _7-20 bridged cycloalkyl", "C _5-15 bridged cycloalkyl" and "C _7-15 bridged cycloalkyl", representative examples of which include, but are not limited to, adamantylene, diamantane, ice-sheet, bicyclo [2.2.1] heptane subunit, 2-oxo-bicyclo [2.2.1] heptane subunit, bicyclo [2.2.1] heptene subunit, and cuban. The "C _5-30 -bridged cycloalkyl" is optionally further substituted with one or more (e.g., 1-10, 1-6, 1-5, 1-4, or 1-3) groups each independently selected from deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, oxo, optionally deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, Optionally deuterated C _3-6 cycloalkyl, optionally deuterated C _1-6 alkoxy, halogenated C _1-6 alkoxy, optionally deuterated C _1-6 alkyl-NH- NH ₂-C_1-6 alkylene, optionally deuterated C _1-6 alkyl-NHC (O) -, optionally deuterated C _1-6 alkyl-C (O) NH-, C _2-6 alkynyl, C _2-6 alkenyl or any combination thereof.

The term "heterocyclyl" or "heterocycloalkyl" as used herein, alone or in combination, refers to a saturated or partially unsaturated (i.e., having one or more double bonds, but not fully conjugated) cyclic hydrocarbon radical containing one or more (e.g., containing 1 to 5, 1 to 4, 1 to 3, 1 to 2, or 1) heteroatoms independently selected from sulfur, oxygen, and nitrogen, optionally 4 to 30, 4 to 25, 4 to 20, 4 to 15, 4 to 14, 4 to 13, 4 to 12, 4 to 11, 4 to 10, 4 to 9, 4 to 8, 4 to 7, 4 to 6, 4 to 5,5 to 9, 5 to 30, 5 to 20, or 5 to 15. Examples of the term "heterocyclyl" include, but are not limited to, monocyclic heterocyclyl (e.g., 4 to 30 membered monocyclic heterocyclyl and 4 to 20 membered monocyclic heterocyclyl), bridged heterocyclyl (e.g., 5 to 30 membered bridged heterocyclyl, 5 to 20 membered bridged heterocyclyl, 7 to 20 membered bridged heterocyclyl, and 7 to 15 membered bridged heterocyclyl), fused heterocyclyl (e.g., 5 to 30 membered fused heterocyclyl and 5 to 20 membered fused heterocyclyl), and spiroheterocyclyl (e.g., 5 to 30 membered spiroheterocyclyl and 5 to 20 membered spiroheterocyclyl). Representative examples of monocyclic heterocyclyl groups include, but are not limited to, azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothienyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, dioxanyl, azepanyl, azacyclooctyl, diazepanyl (e.g., 1, 4-diazepan-1-yl), and diazepanyl. Examples of bridged heterocyclyl, fused heterocyclyl, and spiroheterocyclyl groups include, but are not limited to, 6-azabicyclo [3.1.1] heptan-3-yl, 2, 5-diazabicyclo [2.2.1] heptan-2-yl, 3, 6-diazabicyclo [3.1.1] heptan-3-yl, 3-azabicyclo [3.2.1] octan-8-yl, 3, 8-diazabicyclo [3.2.1] octan-3-yl, 2, 5-diazabicyclo [2.2.2] octan-2-yl, quinine, octahydro-1H-indolyl, pyrrolidinyl-cyclopropyl, Cyclopentyl aziridinyl, pyrrolidinyl-cyclobutyl, pyrrolidinyl-pyrrolidinyl (e.g., hexahydropyrrolo [3,4-c ] pyrrolyl), pyrrolidinyl-piperidinyl, pyrrolidinyl-piperazinyl, pyrrolidinyl-morpholinyl, piperidinyl-morpholinyl, and azaspirocyclic groups (e.g., 5-to 20-membered azaspirocyclic groups, such as 3-azaspiro [5.5] undec-3-yl and 7-azaspiro [3.5] nonanyl). The heterocyclic group may be unsubstituted or substituted (e.g. mono-, di-, tri-, or polysubstituted) as well defined, wherein the substituents are optionally selected from deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, oxo, optionally deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, optionally deuterated C _3-6 cycloalkyl, Optionally deuterated C _1-6 alkoxy, halogenated C _1-6 alkoxy, optionally deuterated C _1-6 alkyl-NH-, NH ₂-C_1-6 alkylene, Optionally deuterated C _1-6 alkyl-NHC (O) -, optionally deuterated C _1-6 alkyl-C (O) NH-, C _2-6 alkynyl, C _2-6 alkenyl, or any combination thereof.

The term "nitrogen-containing heterocyclyl" or "nitrogen-containing heterocycloalkyl", as used herein, alone or in combination, refers to a 4 to 30 membered (e.g., 4 to 30 membered, 4 to 25 membered, 4 to 20 membered, 4 to 15 membered, 4 to 14 membered, 4 to 13 membered, 4 to 12 membered, 4 to 11 membered, 4 to 10 membered, 4 to 9 membered, 4 to 8 membered, 4 to 7 membered, 4 to 6 membered, 4 to 5 membered, 5 to 9 membered, 5 to 30 membered, 5 to 20 membered, or 5 to 15 membered) monocyclic ring containing one nitrogen atom and optionally containing one or more heteroatoms (e.g., 1 to 5,1 to 3,1 to 2, or 1) independently selected from sulfur, oxygen, and nitrogen, a bicyclic, tricyclic or polycyclic saturated or partially unsaturated (i.e., having one or more double bonds, but not fully conjugated) cycloalkyl group. Examples of the term "nitrogen-containing heterocyclic group" include, but are not limited to, nitrogen-containing monocyclic heterocyclic groups (e.g., 4 to 30 membered nitrogen-containing monocyclic heterocyclic groups and 4 to 20 membered nitrogen-containing monocyclic heterocyclic groups), nitrogen-containing bridged heterocyclic groups (e.g., 5 to 30 membered nitrogen-containing bridged heterocyclic groups, 5 to 20 membered nitrogen-bridged heterocyclic groups, 5 to 15 membered nitrogen-bridged heterocyclic groups, 7 to 20 membered nitrogen-bridged heterocyclic groups, or 7 to 15 membered nitrogen-bridged heterocyclic groups), nitrogen-containing fused heterocyclic groups (e.g., 5 to 30 membered nitrogen-containing fused heterocyclic groups and 5 to 20 membered nitrogen-containing fused heterocyclic groups), and nitrogen-containing spiro heterocyclic groups (e.g., 5 to 30 membered nitrogen-containing spiro heterocyclic groups and 5 to 20 membered nitrogen-containing spiro heterocyclic groups). Representative examples of nitrogen-containing monocyclic heterocycles include, but are not limited to, azetidinyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, azepanyl, diazepinyl (e.g., 1, 4-diazepin-1-yl), and diazepinyl. Examples of nitrogen-bridged heterocyclyl, nitrogen-fused heterocyclyl, and nitrogen-spiro heterocyclyl include, but are not limited to, 6-azabicyclo [3.1.1] heptan-3-yl, 2, 5-diazabicyclo [2.2.1] heptan-2-yl, 3, 6-diazabicyclo [3.1.1] heptan-3-yl, 3-azabicyclo [3.2.1] octan-8-yl, 3, 8-diazabicyclo [3.2.1] octan-3-yl, 2, 5-diazabicyclo [2.2.2] octan-2-yl, quinine, octahydro-1H-indolyl, pyrrolidinyl, cyclopropyl, Cyclopentyl aziridinyl, pyrrolidinyl-cyclobutyl, pyrrolidinyl-pyrrolidinyl (e.g., hexahydropyrrolo [3,4-c ] pyrrolyl), pyrrolidinyl-piperidinyl, pyrrolidinyl-piperazinyl, pyrrolidinyl-morpholinyl, piperidinyl-morpholinyl, and azaspirocyclic groups (e.g., 5-to 20-membered azaspirocyclic groups, such as 3-azaspiro [5.5] undec-3-yl and 7-azaspiro [3.5] nonanyl). The nitrogen-containing heterocyclic group may be unsubstituted or substituted (e.g., mono-, di-, tri-, or polysubstituted) as well-defined, wherein the substituents are optionally selected from deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, oxo, optionally deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, optionally deuterated C _3-6 cycloalkyl, Optionally deuterated C _1-6 alkoxy, halogenated C _1-6 alkoxy, optionally deuterated C _1-6 alkyl-NH-, NH ₂-C_1-6 alkylene, Optionally deuterated C _1-6 alkyl-NHC (O) -, optionally deuterated C _1-6 alkyl-C (O) NH-, C _2-6 alkynyl, C _{2- 6} alkenyl, or any combination thereof.

The term "heterocyclylene" or "heterocycloalkylene", as used herein, alone or in combination, refers to a4 to 30 membered monocyclic, bicyclic, tricyclic, or polycyclic saturated or partially unsaturated (i.e., having one or more double bonds, but not fully conjugated) divalent cyclic hydrocarbon radical containing one or more (e.g., containing 1 to 5,1 to 4, 1 to 3, 1 to 2, or 1) heteroatoms independently selected from sulfur, oxygen, and nitrogen. Examples of the term "heterocyclylene" include, but are not limited to, monocyclic heterocyclylene (e.g., 4 to 30 membered monocyclic heterocyclylene, and 4 to 20 membered monocyclic heterocyclylene), bridged heterocyclyl (e.g., 5 to 30 membered bridged heterocyclyl, 5 to 20 membered bridged heterocyclyl, 7 to 20 membered bridged heterocyclyl, or 7 to 15 membered bridged heterocyclyl), fused heterocyclyl (e.g., 5 to 30 membered fused heterocyclyl, and 5 to 20 membered fused heterocyclyl), and spiro heterocyclyl (e.g., 5 to 30 membered spiro heterocyclyl, and 5 to 20 membered spiro heterocyclyl). Representative examples of monocyclic heterocycloalkylene include, but are not limited to, azetidinylene, oxetylene, pyrrolidinylene, imidazolidinylene, pyrazolidinylene, tetrahydrofuranylene, dihydropyranyl, tetrahydropyranyl, tetrahydrothiophenylene, tetrahydrothiopyranylene, oxazolidinylene, thiazolidinylene, piperidylene, piperazinylene, morpholinylene, thiomorpholinylene, azepanylene, azetidinylene, dioxanyl, diazepanylene (e.g., 1, 4-diazepanylene, 4, 5-diazepanylene, 1, 3-diazepanylene) and diazepanylene. Examples of bridged heterocyclyl, fused heterocyclyl and spiroheterocyclyl groups include, but are not limited to, 6-azabicyclo [3.1.1] heptane, 2, 5-diazabicyclo [2.2.1] heptane, 3, 6-diazabicyclo [3.1.1] heptane, 3-azabicyclo [3.2.1] octane, 3, 8-diazabicyclo [3.2.1] octane, 2, 5-diazabicyclo [2.2.2] octane, quinuclidinyl, octahydro-1H-indole, pyrrolidino-cyclopropene, cyclopentyl-aziridine, pyrrolidino-cyclobutene, pyrrolidino-pyrrolidine (e.g., hexahydropyrrolo [3,4-c ] pyrrole), pyrrole, Pyrrolidino-piperidines, pyrrolidino-piperazines, pyrrolidino-morpholines, piperidinyl-morpholines, and azaspirocyclic groups (e.g., 5 to 20 membered azaspirocyclic groups such as 3-azaspiro [5.5] undecanes and 7-azaspiro [3.5] nonanes). The heterocyclylene may be unsubstituted or substituted (e.g. mono-, di-, tri-, or polysubstituted) as well defined, wherein the substituents are selected from deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, oxo, optionally deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, optionally deuterated C _3-6 cycloalkyl, Optionally deuterated C _1-6 alkoxy, halogenated C _1-6 alkoxy, optionally deuterated C _1-6 alkyl-NH-, NH ₂-C_1-6 alkylene, Optionally deuterated C _1-6 alkyl-NHC (O) -, optionally deuterated C _1-6 alkyl-C (O) NH-, C _2-6 alkynyl, C _2-6 alkenyl, or any combination thereof.

The term "nitrogen-containing heterocyclylene" or "nitrogen-containing heterocycloalkylene", as used herein, alone or in combination, refers to a 4 to 30 membered (e.g., 4 to 30 membered, 4 to 25 membered, 4 to 20 membered, 4 to 15 membered, 4 to 14 membered, 4 to 12 membered, 4 to 11 membered, 4 to 10 membered, 4 to 9 membered, 4 to 8 membered, 4 to 7 membered, 4 to 6 membered, 4 to 5 membered, 5 to 9 membered, 5 to 30 membered, 5 to 20 membered, or 5 to 15 membered) monocyclic ring containing one nitrogen atom and optionally containing one or more heteroatoms (e.g., containing 1 to 5, 1 to 4, 1 to 3, 1 to 2, or 1) independently selected from sulfur, oxygen, and nitrogen, A bicyclic, tricyclic or polycyclic saturated or partially unsaturated (i.e., having one or more double bonds, but not fully conjugated) divalent cyclic hydrocarbon group. Examples of the term "nitrogen-containing heterocyclylene" include, but are not limited to, nitrogen-containing monocyclic heterocyclylene (e.g., 4 to 30 membered nitrogen-containing monocyclic heterocyclylene, and 4 to 20 membered nitrogen-containing monocyclic heterocyclylene), nitrogen-containing bridged heterocyclylene (e.g., 5 to 30 membered nitrogen-containing bridged heterocyclyl, 5 to 20 membered nitrogen-containing bridged heterocyclyl, 7 to 20 membered nitrogen-containing bridged heterocyclyl, or 7 to 15 membered nitrogen-containing bridged heterocyclyl), nitrogen-containing fused heterocyclylene (e.g., 5 to 30 membered nitrogen-containing fused heterocyclylene and 5 to 20 membered nitrogen-containing fused heterocyclylene), and nitrogen-containing spiro-ylene (e.g., 5 to 30 membered nitrogen-containing spiro-ylene and 5 to 20 membered nitrogen-containing spiro-phenylene). Representative examples of nitrogen-containing monocyclic heterocycles include, but are not limited to, azetidinyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, oxazolidinyl, thiazolidinyl, piperidyl, piperazinyl, morpholinyl, thiomorpholinyl, azepanyl, azacyclooctyl, diazepanyl (e.g., 1, 4-diazepanyl, 4, 5-diazepanyl, 1, 3-diazepanyl) and diazepanyl. examples of nitrogen-containing bridged heterocyclyl, nitrogen-containing fused heterocyclyl and nitrogen-containing spiroheterocyclyl include, but are not limited to, 6-azabicyclo [3.1.1] heptane, 2, 5-diazabicyclo [2.2.1] heptane, 3, 6-diazabicyclo [3.1.1] heptane, 3-azabicyclo [3.2.1] octane, 3, 8-diazabicyclo [3.2.1] octane, 2, 5-diazabicyclo [2.2.2] octane, quinine, octahydro-1H-indole, pyrrolidino-cyclopropene, cyclopento-azacyclopropene, pyrrolidino-cyclobutene, pyrrolidino-pyrrolidine (e.g., hexahydropyrrolo [3,4-c ] pyrrole), Pyrrolidino-piperidines, pyrrolidino-piperazines, pyrrolidino-morpholines, piperidinyl-morpholines, and azaspirocyclic groups (e.g., 5 to 20 membered azaspirocyclic groups such as 3-azaspiro [5.5] undecanes and 7-azaspiro [3.5] nonanes). The nitrogen-containing heterocyclylene may be unsubstituted or substituted (e.g., mono-, di-, tri-, or polysubstituted) as well-defined, wherein the substituents are selected from deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, oxo, optionally deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, optionally deuterated C _3-6 cycloalkyl, Optionally deuterated C _1-6 alkoxy, halogenated C _1-6 alkoxy, optionally deuterated C _1-6 alkyl-NH-, NH ₂-C_1-6 alkylene, Optionally deuterated C _1-6 alkyl-NHC (O) -, optionally deuterated C _1-6 alkyl-C (O) NH-, C _2-6 alkynyl, C _2-6 alkenyl, or any combination thereof.

The term "monoazacyclosubunit", as used herein, alone or in combination, refers to a 5 to 30 membered (e.g., 5 to 30 membered, 5 to 25 membered, 5 to 20 membered, 5 to 15 membered, 5 to 14 membered, 5 to 12 membered, 5 to 11 membered, 5 to 10 membered, 5 to 9 membered, 5 to 8 membered, 5 to 7 membered, 5 to 6 membered, 7 to 30 membered, 7 to 20 membered, or 7 to 15 membered) bicyclic, tricyclic, or polycyclic saturated or partially unsaturated (i.e., having one or more double bonds, but not fully conjugated) divalent bridged cyclic hydrocarbon group containing one nitrogen atom. Examples of monoazacyclosubunits include, but are not limited to, 6-azabicyclo [3.1.1] heptane subunits, 3-azabicyclo [3.2.1] octane subunits, and quinuclidine groups. The monoazacyclosubunit may be unsubstituted or substituted as well defined (e.g. by one or more substituents) selected from deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, oxo, optionally deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, optionally deuterated C _3-6 cycloalkyl, optionally deuterated C _1-6 alkoxy, halogenated C _1-6 alkoxy, optionally deuterated C _1-6 alkyl-NH-, NH ₂-C_1-6 alkylene, optionally deuterated C _1-6 alkyl-NHC (O) -, optionally deuterated C _1-6 alkyl-C (O) NH-, C _2-6 alkynyl, C _2-6 alkenyl, or any combination thereof. The number of substituents is in principle not subject to any restrictions or is automatically limited by the size of the building block. For example, the number of substituents may be one or more, such as 1-20, 1-15, 1-10, 1-6, 1-4, 1-3, 2-6, or 1.

The term "mono-aza spirocyclic subunit", as used herein, alone or in combination, refers to a 5 to 30 membered (e.g., 5 to 30 membered, 5 to 25 membered, 5 to 20 membered, 5 to 15 membered, 5 to 14 membered, 5 to 12 membered, 5 to 11 membered, 5 to 10 membered, 5 to 9 membered, 5 to 8 membered, 5 to 7 membered, 5 to 6 membered, 7 to 30 membered, 7 to 20 membered, or 7 to 15 membered) bicyclic, tricyclic, or partially unsaturated (i.e., having one or more double bonds, but not fully conjugated) divalent spirocyclic hydrocarbon group containing one nitrogen atom. Examples of mono-azaspiro subunits include, but are not limited to, 3-azaspiro [5.5] undecane subunit and 7-azaspiro [3.5] nonane subunit. The mono-aza spirocyclic subunit may be unsubstituted or substituted as well defined (e.g. by one or more substituents) selected from deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, oxo, optionally deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, optionally deuterated C _3-6 cycloalkyl, optionally deuterated C _1-6 alkoxy, halogenated C _1-6 alkoxy, optionally deuterated C _1-6 alkyl-NH-, NH ₂-C_1-6 alkylene, optionally deuterated C _1-6 alkyl-NHC (O) -, optionally deuterated C _1-6 alkyl-C (O) NH-, C _2-6 alkynyl, C _2-6 alkenyl or any combination thereof. The number of substituents is in principle not subject to any restrictions or is automatically limited by the size of the building block. For example, the number of substituents may be one or more, such as 1-20, 1-15, 1-10, 1-6, 1-4, 1-3, 2-6, or 1.

The term "alkynyl", as used herein, alone or in combination, refers to a straight or branched chain monovalent hydrocarbon radical containing 2 to 8 (e.g., 2 to 6, 2 to 5, 2 to 4, more preferably 2) carbon atoms having one or more (e.g., 1 to 3, 1 to 2, or 1) carbon-carbon triple bonds. Examples of "alkynyl" include C _2-8 alkynyl, C _2-6 alkynyl, or C _2-4 alkynyl, representative examples of which include, but are not limited to, ethynyl, 1-propynyl, 1-butynyl, and 1, 3-dialkynyl.

The term "alkenyl" as used herein, alone or in combination, refers to a straight or branched chain monovalent hydrocarbon radical containing 2 to 8 carbon atoms (e.g., 2 to 6, 2 to 5, or 2 to 4, 2 to 3, or 2 carbon atoms) having one or more (e.g., 1 to 3, 1 to 2, or 1) carbon-carbon double bonds. Examples of "alkenyl" include C _2-8 alkenyl, C _2-6 alkenyl, or C _2-4 alkenyl, representative examples of which include, but are not limited to, vinyl (e.g., CH ₂ =ch-), 1-propenyl, allyl, 1-butenyl, 2-butenyl, 3-butenyl, isobutenyl, pentenyl, n-penta-2, 4-dienyl, 1-methyl-but-1-enyl, 2-methyl-but-1-enyl, 3-methyl-but-1-enyl, 1-methyl-but-2-ylidene, 2-methyl-but-2-ylidene, 1-methyl-but-3-enyl, 2-methyl-but-3-enyl, 3-methyl-but-3-enyl, and hexenyl.

In this context, the term "borneol" or "bornane" (also known as1, 7-trimethylbicyclo [2.2.1] heptane; camphane; boranylane) has a definition known to the person skilled in the art. As used herein, the term "bornyl" or "borneol" refers to a monovalent radical of a bornane, i.e., the radical remaining after any hydrogen in the bornane has been removed. Representative examples of "ice flake groups" include, but are not limited to, 1, 7-trimethylbicyclo [2.2.1] heptan-2-yl, 1, 7-trimethylbicyclo [2.2.1] heptan-3-yl, 1, 7-trimethylbicyclo [2.2.1] heptan-4-yl, 1, 7-trimethylbicyclo [2.2.1] heptan-5-yl, or 1, 7-trimethylbicyclo [2.2.1] heptan-6-yl,

In this context, the term "bicyclo [2.2.1] heptane" (also known as bicyclo [2.2.1] heptane) or "norbornane" has the definition that is known to the person skilled in the art as Ra. As used herein, "bicyclo [2.2.1] heptyl" or "norbornyl" refers to a monovalent group of bicyclo [2.2.1] heptane, i.e., the group remaining after any hydrogen in the bicyclo [2.2.1] heptane has been removed. Representative examples of "bicyclo [2.2.1] heptanyl" include, but are not limited to, bicyclo [2.2.1] heptan-2-yl, bicyclo [2.2.1] heptan-3-yl, bicyclo [2.2.1] heptan-4-yl, bicyclo [2.2.1] heptan-5-yl, and bicyclo [2.2.1] heptan-6-yl.

The term "bicyclo [2.2.1] heptene" is also referred to herein as bicyclo [2.2.1] hepene, having a definition known to those skilled in the art. As used herein, "bicyclo [2.2.1] heptenyl" refers to a monovalent group of a bicyclo [2.2.1] heptene, i.e., the group remaining after any hydrogen in the bicyclo [2.2.1] heptene is removed. Representative examples of "bicyclo [2.2.1] heptenyl" include, but are not limited to, bicyclo [2.2.1] hept-5-en-2-yl, bicyclo [2.2.1] hept-5-en-3-yl, and bicyclo [2.2.1] hept-5-en-7-yl.

In this context, the term "adamantane" (also known as Tricyclo [3.3.1.1 ^3,7 ] decane) has a definition known to the person skilled in the art, the structural formula of which is for example as follows: Herein, "adamantyl" refers to a monovalent group of adamantane, i.e., a group remaining after any hydrogen in adamantane is removed. Representative examples of "adamantyl" include, but are not limited to, 1-adamantyl, 2-adamantyl, 3-adamantyl, 4-adamantyl, 5-adamantyl, 6-adamantyl, 7-adamantyl, 8-adamantyl, 9-adamantyl, and 10-adamantyl.

In this context, the term "noradamantane" (also known as noradamantane, or octahydro-2,5-methanopentalene (translation: octahydro-2, 5-methanocyclopentadiene)) has a definition known to those skilled in the art, the structural formula of which is for example as follows: In this context, "noradamantyl" refers to a monovalent group of noradamantane, i.e., the group remaining after any hydrogen in the noradamantane has been removed. Representative examples of "adamantyl" include, but are not limited to, 1-adamantyl, 2-adamantyl, 3-adamantyl, 4-adamantyl, 5-adamantyl, 6-adamantyl, 7-adamantyl, 8-adamantyl, and 9-adamantyl.

In this context, the term "amantadine" has the definition known to the person skilled in the art, i.e. refers to an adamantane having an amino substituent, wherein the amino group may replace a hydrogen on a carbon at any position of the adamantane. An example of "amantadine" may be amantadine-1-amine (corresponding to the English culture academy name adamantan-1-amine or Tricyclo [ 3.3.1.1. ^3,7 ] decan-1-amine; CAS: 768-94-5), having the formula

Also within the scope of the present disclosure are salts or pharmaceutically acceptable salts, enantiomers, stereoisomers, solvates, prodrugs, polymorphs of the disclosed compounds, including the compounds of formula (I), formula (I-1), formula (I-2), formula (I-3), formula (I-4), formula (I-5), formula (II-1), formula (II-2), formula (II-3), formula (II-4), formula (I').

In all embodiments of the present disclosure, the salts or pharmaceutically acceptable salts of the compounds of formula (I) (and of the compounds of formula (I-1), formula (I-2), formula (I-3), formula (I-4), formula (I-5), formula (II-1), formula (II-2), formula (II-3), formula (II-4), formula (I') refer to non-toxic inorganic or organic acid and/or base addition salts. Examples include: sulfate, hydrohalate (including hydrochloride, hydrobromide), citrate/citrate, maleate, lactate, lactobionate, L-tartrate, fumarate, L-malate, L-lactate, alpha-ketoglutarate, hippurate, D-glucuronate, D-gluconate, alpha-D-glucoheptonate, glycolate, mucinate, L-ascorbate, orotate, picrate, glycinate, alaninate, arginate, cinnamate, laurate, pamoate, sebacate, benzenesulfonate, methanesulfonate, ethanesulfonate, ethanedisulfonate, formate, acetate, 2-dichloroacetate, trimethylacetate, propionate, valerate, palmitate, triphenylacetate, 2-ethyl-succinate, iodate, nicotinate, L-pyroglutamate, L-proline, ferulate, 2-hydroxyethanesulfonate, nitrate, gentisate, cholate, salicylate, terephthalate, glutarate, adipate, stearate, oleate, undecylenate, camphorsulfonate, dodecylsulfonate, phosphate, thiocyanate, dihydrogen phosphate, pyrophosphate, metaphosphate, oxalate, carbonate, malonate, benzoate, mandelate, succinate, pyruvate, p-chlorobenzenesulfonate, 1, 5-naphthalenedisulfonate, 3-hydroxy-2-naphthoate, 1-hydroxy-2-naphthoate, 2-naphthalenesulfonate, glycolate, trifluoroacetate, terephthalate, and p-toluenesulfonate, and the like.

By "pharmaceutically acceptable carrier" is meant a pharmaceutically acceptable material, such as a filler, stabilizer, dispersant, suspending agent, diluent, excipient, thickener, solvent, or encapsulating material, that carries or transports the compounds useful in the present disclosure into a patient or to a patient so that they can perform their intended function. Typically, such constructs are carried or transported from one organ or body part to another organ or body part. The carrier is compatible with the other ingredients of the formulation, including the compounds useful in this disclosure, and not deleterious to the patient, and must be "acceptable". Some examples of materials that may be used as pharmaceutically acceptable carriers include sugars such as lactose, dextrose, and sucrose, starches such as corn starch and potato starch, celluloses and derivatives thereof such as sodium carboxymethyl cellulose, ethyl cellulose, and cellulose acetate, powdered tragacanth, malt, gelatin, talc, excipients such as cocoa butter and suppository waxes, oils such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and soybean oil, glycols such as propylene glycol, polyols such as glycerin, sorbitol, mannitol, and polyethylene glycols, esters such as ethyl oleate and ethyl laurate, agar, buffers such as magnesium hydroxide and aluminum hydroxide, surfactant phosphate buffers, and other non-toxic compatible materials used in pharmaceutical formulations.

The term "room temperature" of the present disclosure refers to the ambient temperature, e.g., a temperature of 20-30 ℃.

Herein, "stereoisomers" refer to compounds having the same chemical structure, but different arrangements of atoms or groups in space. Stereoisomers include enantiomers, diastereomers, conformational isomers (rotamers), geometric isomers (cis/trans), atropisomers, and the like.

As used herein, the term "solvate" refers to an association or complex of one or more solvent molecules and a compound of the present invention. Examples of solvents include water, isopropanol, ethanol, methanol, DMSO, ethyl acetate, acetic acid, and ethanolamine. The term "hydrate" refers to a complex in which the solvent molecule is water.

In this context, the term "chiral" refers to a molecule that has properties that do not overlap with its mirror image, while "achiral" refers to a molecule that can overlap with its mirror image.

In this context, the term "enantiomer" refers to two isomers of a compound that do not overlap but are in mirror image relationship to each other.

In this context, the term "diastereoisomer" refers to stereoisomers which have two or more chiral centers and whose molecules are not mirror images of each other. Diastereomers have different physical properties, such as melting point, boiling point, spectral properties, and reactivity. The diastereomeric mixture may be separated by high resolution analytical procedures such as electrophoresis and chromatography, e.g., HPLC.

In this context, the term "prodrug" refers to a compound that can be converted into its active form having biological activity in vivo, for example by hydrolysis in the blood. When the prodrug is administered to a patient, it releases the parent compound in vivo. Prodrugs are typically prepared by modification of functional groups, which may be removed by conventional procedures (e.g., acid/base hydrolysis) or cleavage in vivo, to release the parent drug. Prodrugs include, for example, compounds of the invention in which a hydroxy, amino or sulfhydryl group is bonded to any group that, when administered to a patient, cleaves to reform the hydroxy, amino or sulfhydryl group. Representative examples of prodrugs therefore include, but are not limited to, acetate, formate, tert-butoxycarbonyl (Boc) and benzoate/amide derivatives of hydroxy, mercapto and amino functional groups of compounds of formula (I) and (II). In addition, in the case of carboxylic acid (-COOH), esters such as methyl ester, ethyl ester, etc. may be used. These esters may be active themselves and/or may hydrolyze under conditions in the human body. Suitable pharmaceutically acceptable, in vivo hydrolysable ester groups include those which readily decompose in the human body to release the parent acid or salt thereof.

In this context, "p-menthane" (also known as p-methane) has a definition known to those skilled in the art, and has the structural formula shown below, for example: As used herein, "p-menthyl" refers to a monovalent group of p-menthane, i.e., the group remaining after removal of any one of the hydrogens on the carbon at any position of the p-menthane. Representative examples include, but are not limited to

In this context, "m-menthane" (also known as m-methane) has a definition known to those skilled in the art, and has the structural formula shown below, for example: As used herein, "m-menthyl" refers to a monovalent group of m-menthane, i.e., the group remaining after any hydrogen on the carbon at any position of m-menthane has been removed. Representative examples include, but are not limited to

Herein, "quinuclidine" (also known as Quinuclidine), having the chemical name 1-azabicyclo [2.2.2] octane, has a definition known to those skilled in the art, and has the structural formula shown, for example, as follows: Herein, "quinuclidinyl" refers to a monovalent group of the quinuclidine, i.e., the group remaining after removal of any one of the hydrogens on the carbon at any position of the quinuclidine. Representative examples include, but are not limited to

Drawings

FIG. 1 shows the results of a Western Blot experiment of the degradation of target substrate proteins in hBMC cells by the compounds of the invention.

Examples

In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present invention. The present invention may be practiced without some or all of these specific details. In other instances, well known process operations have not been described in detail in order not to unnecessarily obscure the present invention. While the invention will be described in conjunction with the specific embodiments, it will be understood that they are not intended to limit the invention to these embodiments.

The following abbreviations are used throughout the specification and examples for AcOH acetic acid Boc tert-butoxycarbonyl DCM dichloromethane DIEA or DIPEA N, N-diisopropylethylamine DMF N, N-dimethylformamide DMSO dimethyl sulfoxide EA ethyl acetate ESI electrospray ionization equiv equivalent EtOH ethanol EtOAc ethyl acetate HPLC high performance liquid chromatography HRMS high resolution mass spectrometry LC-MS liquid chromatography-mass spectrometry combined with LRMS low resolution mass spectrometry LC liquid chromatography MeMeMeMeMeMeCN acetonitrile MeOH methanol MS mass spectrometry MsCl methanesulfonyl chloride MsO-methanesulfonyloxy Ms ₂ O methanesulfonic anhydride ¹ H NMR nuclear magnetic resonance hydrogen spectrum MeO-methoxy ONs O-nitrobenzenesulfonyl rt room temperature tBu tert-butyl TEA triethylamine TFO-trifluoro methanesulfonyloxy TLC TMS trimethylsilyl TsO-p-toluenesulfonyloxy Xants 4, 5-bis (diphenylphosphine) -9, 9-dimethylxanthene X-Phos 2-dicyclohexylphosphine-2 ',4',6' -triisopropyl biphenyl

In the present invention ¹ H NMR spectra were measured using Bruker-500MHz type NMR, CD ₃ OD (delta=3.31 ppm) containing 0.1% TMS as an internal standard, CDCl ₃ (delta=7.26 ppm) containing 0.1% TMS as an internal standard, DMSO-d ₆ (delta=2.50 ppm) containing 0.03% TMS as an internal standard, LC-MS spectra were measured on a Sciex API 2000 type mass spectrometer with an Agilent 1100 binary pump and DAD and ELSD or on an Agilent1260-6125B type single quadrupole liquid-mass spectrometer with an Agilent quaternary pump, DAD and ELSD, HPLC preparation was measured on an SHIMADZU LC-20AP type instrument, HPLC purity was measured on SHIMADZU LC-30AP or Waters 1525 type, and separation by supercritical fluid chromatography (C) was carried out on an apparatus equipped with an Agilent quaternary pump, DAD and ELSD type single quadrupole liquid-mass spectrometerThe SHIMADZU LC-20AP apparatus of IE column. All reactions were carried out under an air atmosphere and were followed by TLC or LC-MS.

The solvents and reagents were prepared by the solvents DCM, DMF, etOH and MeOH were all purchased from the national drug group, by the preparation of HPLC using preparation grade CH ₃ CN and deionized water, and other reaction substrates, reagents and drugs were purchased directly from commercial sources, or were synthesized by methods known in the art, without any particular explanation.

The materials and reagents used in the examples below, unless otherwise indicated, are all commercially available for direct use or may be synthesized using or according to methods known in the art.

General synthetic method

The compounds described in this disclosure and/or pharmaceutically acceptable salts thereof can be synthesized using commercially available starting materials by synthetic techniques known in the art. The synthetic schemes described below exemplify the preparation of most compounds. The starting materials or reagents used in each scheme are commercially available or can be prepared by methods known to those skilled in the art. Salts, racemates, enantiomers, phosphates, sulphates, hydrochlorides and prodrug forms of the compounds of formula (I) of the present disclosure may be prepared by those skilled in the art according to conventional techniques in the art.

Synthesis scheme 1: Scheme 1

In scheme 1, Z, R _a1、R_a2、R_a3、R_a4、(R_a5)_m, ring B, (R _d2)_n2, m1, ring C, and (R _d3)_n3) are as defined in the compounds of formula (I) and sub-embodiments thereof of the present disclosure, (I) R _La1 and R _La3 represent N (R _w),R_La2 represents)R _La4 representsWherein R _w, ring A ₁、(R_d1)_n1 are as defined in the compounds of formula (I) and sub-embodiments thereof of the present disclosure, or (ii) R _La1 and R _La3 representR _La2 represents-NH ₂,R_La4 or-N= -, or (iii) R _La1 and R _La3 represent NH, R _La2 represents-NH ₂,R_La4 represents NH or-N= -, or (iv) R _La2 representsWherein ring A ₂、(R_d4)_n4 is as defined in the compounds of formula (I) of the present disclosure and the sub-embodiments thereof, R _La1 and R _La3 representThe symbol indicates the point of attachment to ring a ₂, and R _La4 represents

The reductive amination reaction in scheme 1 can be conventional techniques and methods well known to those skilled in the art. For example, the reductive amination reaction may be carried out in the presence of sodium borohydride acetate and N, N-dimethylformamide, or sodium cyanoborohydride and 1, 2-dichloroethane, at room temperature to 80 ℃ (e.g., room temperature to 50 ℃,40 ℃ -60 ℃,40 ℃ -50 ℃, or 50 ℃ -60 ℃). The molar ratio of substrate 1-1 to substrate 1-2 may be for example, 1:1.1-3, 1:1.1-2, 1:1.1-1.5, 1:1.1-1.2, or 1:1.2 to 1.3.

For example, the specific operation of scheme 1 may be as follows:

Substrate 1-1 (1.0 eq.) and aldehyde substrate 1-2 (2.0 eq.) were dissolved in N, N-dimethylformamide and AcOH (1 drop) was added to the solution. The reaction solution was stirred at 50 ℃ for 2 hours, then cooled to room temperature, and then sodium borohydride acetate (4.0 eq.) was added to the reaction solution, followed by stirring for 17 hours. LCMS detects completion of the reaction. The reaction solution is filtered, and the filtrate is purified by high performance liquid chromatography to obtain the target compound.

Synthesis scheme 2: Scheme 2

In scheme 2, Z, R _a1、R_a2、R_a3、R_a4、(R_a5)_m、R_c2, ring B, (R _d2)_n2, m1, ring C, and (R _d3)_n3) are as defined in the compounds of formula (I) and sub-embodiments thereof of the present disclosure the group LE represents Cl, br, I, OMs, OTs, or ONs. In scheme 2, (I) R _Lb1 and R _Lb3 represent NH, R _Lb2 representsR _Lb4 representsWherein ring A ₁、(R_d1)_n1 is as defined in the compound of formula (I) and its various sub-embodiments of the disclosure, or (ii) R _Lb1 and R _Lb3 and represent NH, R _Lb2 represents-NH ₂,R_Lb4 represents NH, or (iii) R _Lb1 and R _Lb3 representR _Lb2 represents-NH ₂,R_Lb4 represents NH, wherein ring A ₁、(R_d1)_n1 is as defined in the compounds of formula (I) and sub-embodiments thereof of the present disclosure, or (iv) R _Lb2 representsWherein ring A ₂、(R_d4)_n4 is as defined in the compounds of formula (I) of the present disclosure and the sub-embodiments thereof, R _Lb1 and R _Lb3 representThe symbol indicates the point of attachment to ring a ₂, and R _Lb4 represents

The amine alkylation reaction in scheme 2 may be carried out, for example, in the presence of DIEA and sodium iodide, or triethylamine and sodium iodide, at room temperature to 80 ℃ (e.g., 40 ℃ -60 ℃, 40 ℃ -50 ℃, or 50 ℃ -60 ℃). The molar ratio of substrate 2-1 to substrate 2-2 may be, for example, 1:1.1-2, 1:1.1-1.5, 1:1.1-1.2, or 1:1.2-1.3, etc.

For example, the specific operation of scheme 2 may be as follows:

Substrate 2-1 (1.0 eq.) and substrate 2-2 (1.2 eq.) were dissolved in N, N-dimethylformamide, triethylamine (3.0 eq.) and sodium iodide (1.0 eq.) were added to the solution, and the reaction solution was stirred at room temperature for 18 hours. LCMS detects completion of the reaction. The reaction solution is filtered, and the filtrate is purified by high performance liquid chromatography to obtain the target compound.

Synthesis scheme 3: Scheme 3

In scheme 3, Z, R _a1、R_a2、R_a3、R_a4、(R_a5)_m, ring B, (R _d2)_n2, m1, ring C, and (R _d3)_n3) are as defined in the compounds of formula (I) and sub-embodiments thereof of the present disclosure, (I) R _Lc1 and R _Lc3 and represents NH, R _Lc2 representsR _Lc4 representsWherein ring A ₁、(R_d1)_n1 is as defined in the compound of formula (I) and its various sub-embodiments of the disclosure, or (ii) R _Lc1 and R _Lc3 and represent NH, R _Lc2 represents-NH ₂,R_Lc4 represents NH, or (iii) R _Lc1 and R _Lc3 representR _Lc2 represents-NH ₂,R_Lc4 represents NH, or (iv) R _Lc2 representsWherein ring A ₂、(R_d4)_n4 is as defined in the compounds of formula (I) of the present disclosure and the sub-embodiments thereof, R _Lc1 and R _Lc3 representThe symbol indicates the point of attachment to ring a ₂, and R _Lc4 represents

The specific operation of scheme 3 may be as follows:

Substrate 3-1 (1.0 eq.) and substrate 3-2 (1.2 eq.) were dissolved in N, N-dimethylformamide, HATU (1.5 eq.) and triethylamine (3.0 eq.) were added to the solution and the reaction stirred at room temperature for 18 hours. LCMS detects completion of the reaction. The reaction solution is filtered, and the filtrate is purified by high performance liquid chromatography to obtain the target compound.

Synthesis scheme 4. Carbamide formation reaction (Urea Formation (Triphosgene))Scheme 4

In scheme 4, Z, R _a1、R_a2、R_a3、R_a4、(R_a5)_m、R_w, ring A ₁、(R_d1)_n1、(R_d2)_n2, m1, ring C, and (R _d3)_n3) are as defined in the compounds of formula (I) of the present disclosure and in their various sub-embodiments, ring B represents a nitrogen-containing heterocycle.

The specific operation of scheme 4 may be as follows:

Substrate 4-2 (1.0 eq.) and triphosgene (0.5 eq.) were dissolved in dichloromethane, triethylamine (3.0 eq.) was added to the solution, and the reaction solution was stirred at room temperature for 0.5 hours. Subsequently, DMF solution of substrate 4-1 was added to the reaction solution, and the reaction solution was stirred for an additional 17 hours. LCMS detects completion of the reaction. The reaction solution is filtered, and the filtrate is purified by high performance liquid chromatography to obtain the target compound.

Synthesis scheme 5: Scheme 5

In scheme 5Z, R _a1、R_a2、R_a3、R_a4、(R_a5)_m is as defined in the compounds of formula (I) of the present disclosure and their sub-embodiments.

The palladium catalyzed coupling reaction in scheme 5 may be conventional techniques and methods well known to those skilled in the art.

General procedure for scheme 5. After the halogenated substrate 5-1 (1.0 eq.) and the amine substrate 5-2 (1.2 eq.) were dissolved in N, N-dimethylformamide, a palladium catalyst (0.2 eq.) and cesium carbonate (3.0 eq.) were added to the solution, the reaction flask was replaced with nitrogen three times and the reaction solution was stirred at 80 ℃ for 18 hours. LCMS detects completion of the reaction. The reaction solution was filtered, and the filtrate was purified by high performance liquid chromatography (eluent (v/v): acetonitrile/0.05% aq.hcl=5% -90%) to give the target compound.

Synthetic scheme A1: Scheme A1

In scheme A1, Z, R _a1、R_a2、R_a3、R_a4、(R_a5)_m、R_w, ring a ₁, and (R _d1)_n1) are as defined in the compounds of formula (I) of the disclosure and sub-embodiments thereof.

The palladium-catalyzed coupling reaction and deprotection in synthetic scheme A1 may be conventional techniques and methods well known to those skilled in the art.

The specific operation of scheme A1 may be as follows:

Step 1 to a 100ml single-necked flask, compound a-1 (1.0 eq.), compound a-1-1 (1.2 eq.), cesium carbonate (2.0 eq.), palladium catalyst (0.025 eq.), and N, N-dimethylformamide were added in this order at room temperature. The reaction mixture was warmed to 80 ℃ under nitrogen and stirred for 16 hours. TLC detection reaction was complete. The reaction mixture was cooled to room temperature, diluted with water, extracted three times with ethyl acetate and the organic phases combined. The combined organic phases were dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was purified by column chromatography to give compound a-1-2 (grey solid, yield 73%).

Step 2 trifluoroacetic acid was added to a dichloromethane solution of compound A-1-2 in a 100mL single-necked flask at room temperature. The reaction was stirred for 1 hour and TLC checked for completion. The reaction solution was concentrated under reduced pressure and lyophilized to give Compound A-1-3.

Synthesis scheme A2: Scheme A2

In scheme A2, Z, R _a1、R_a2、R_a3、R_a4、(R_a5)_m、R_w, ring a ₁, and (R _d1)_n1) are as defined in the compounds of formula (I) of the disclosure and sub-embodiments thereof.

The palladium-catalyzed coupling reaction and deprotection in synthetic scheme A2 may be conventional techniques and methods well known to those skilled in the art.

The specific operation of scheme A2 may be as follows:

Step 1 to a 100ml single-necked flask, compound a-1 (1.0 eq.), compound a-2-1 (1.2 eq.), cesium carbonate (2.0 eq.), palladium catalyst (0.025 eq.), and N, N-dimethylformamide were added in this order at room temperature. The reaction mixture was warmed to 80 ℃ under nitrogen and stirred for 16 hours. TLC detection reaction was complete. The reaction mixture was cooled to room temperature, diluted with water, extracted three times with ethyl acetate and the organic phases combined. The combined organic phases were dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was purified by column chromatography to give compound a-2-2 (grey solid, yield 73%).

Step 2 trifluoroacetic acid was added to a dichloromethane solution of compound A-2-2 in a 100mL single-necked flask at room temperature. The reaction was stirred for 1 hour and TLC checked for completion. The reaction solution is concentrated under reduced pressure and freeze-dried to obtain the compound A-2-3.

Synthetic scheme B1: Scheme B1

In scheme B1, R _a1、R_a2、R_a3、R_a4、R_w, ring a ₁, and (R _d1)_n1 are as defined in the compounds of formula (I) of the disclosure and sub-embodiments thereof, X represents H or F.

Substitution reaction and deprotection in synthetic scheme B1 may be conventional techniques and methods well known to those skilled in the art.

The specific operation of scheme B1 may be as follows:

Step 1, compound B-1 (1.0 eq.) compound B-1-1 (1.2 eq.), N-diisopropylethylamine (5.0 eq.) and dimethyl sulfoxide were added sequentially to a 100 ml single-necked flask at room temperature. The reaction mixture was warmed to 130 ℃ under nitrogen and stirred for 16 hours. TLC detection reaction was complete. The reaction mixture was cooled to room temperature, diluted with water, extracted three times with ethyl acetate and the organic phases combined. The combined organic phases were dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was purified by column chromatography to give compound B-1-2 (grey solid, yield 62%).

Step 2 trifluoroacetic acid was added to a dichloromethane solution of compound B-1-2 in a 100mL single-necked flask at room temperature. The reaction was stirred for 1 hour and TLC checked for completion. The reaction solution is concentrated under reduced pressure and freeze-dried to obtain the compound B-1-3.

Synthesis scheme B2: Scheme B2

In scheme B2, R _a1、R_a2、R_a3、R_a4、R_w, ring a ₁, and (R _d1)_n1 are as defined in the compounds of formula (I) of the disclosure and sub-embodiments thereof, X represents H or F.

Substitution reaction and deprotection in synthetic scheme B2 may be conventional techniques and methods well known to those skilled in the art.

The specific operation of scheme B2 may be as follows:

Step 1, compound B-1 (1.0 eq.), compound B-2-1 (1.2 eq.), N-diisopropylethylamine (5.0 eq.), and dimethyl sulfoxide were added sequentially to a 100 ml single-port bottle at room temperature. The reaction mixture was warmed to 130 ℃ under nitrogen and stirred for 16 hours. TLC detection reaction was complete. The reaction mixture was cooled to room temperature, diluted with water, extracted three times with ethyl acetate and the organic phases combined. The combined organic phases were dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was purified by column chromatography to give compound B-2-2 (grey solid, yield 62%).

Step 2 trifluoroacetic acid was added to a dichloromethane solution of compound B-2-2 in a 100mL single-necked flask at room temperature. The reaction was stirred for 1 hour and TLC checked for completion. The reaction solution is concentrated under reduced pressure and freeze-dried to obtain the compound B-2-3.

Synthetic scheme C: Scheme C

In scheme C, R _a1、R_a2、R_a3、R_a4、Z、(R_a5)_m, ring a ₂, and (R _d4)_n4) are as defined in the compounds of formula (I) of the disclosure and sub-embodiments thereof.

Depending on the target compound, each of the above schemes and its reaction substrate, reaction conditions (including reaction amount, temperature, time, etc.), post-treatment, etc., may be appropriately modified and adjusted by techniques and methods well known to those skilled in the art to obtain the desired target compound, and the obtained target compound may be further modified by substituents, etc., according to methods well known to those skilled in the art to obtain other target compounds.

It will be appreciated that in each of the above synthetic schemes, when the groups contain active hydrogen or reactive groups that do not need to participate in the scheme reaction, the active hydrogen or reactive groups may be protected by techniques and methods well known to those skilled in the art, such as protecting groups. For example, when the reactive group is piperidinyl or piperazinyl, the hydrogen on N may be protected with conventional protecting groups such as Boc and the like. For example, when the reactive group is-CHO, the aldehyde group may be protected with conventional protecting groups, such as to form an acetal. Removal of the protecting group may be accomplished by techniques and methods well known to those skilled in the art, for example, removal of the protecting group Boc may be accomplished under acidic conditions, such as hydrochloric acid, or trifluoroacetic acid. For another example, removal of the acetal protecting group can be accomplished under acidic conditions, such as sulfuric acid, hydrochloric acid, or trifluoroacetic acid. Examples

Example A-1 preparation of Compound GT-04304

The title compound GT-04304 (gray solid, 6.5g, yield 97％).¹H NMR(400MHz,MeOD-d4)δ7.57(d,J＝8.4Hz,1H),7.05(s,1H),6.95(dd,J＝8.4,1.8Hz,1H),5.08(dd,J＝13.3,5.2Hz,1H),4.44-4.31(m,2H),3.38(t,J＝5.1Hz,4H),3.03(s,4H),2.86(dd,J＝13.3,5.3Hz,1H),2.81-2.72(m,1H),2.45(dd,J＝13.1,4.7Hz,1H),2.17-2.09(m,1H).LCMS(ESI)C₁₇H₂₂N₅O₃ ⁺[M+H]⁺： calculated 344.17, found 344.2) was prepared according to the method of synthesis scheme A1.

Example A-2 preparation of Compound GT-06985

The title compound GT-06985 (grey solid, 11.7g, yield 99％).¹H NMR(400MHz,MeOD)δ7.49(d,J＝8.3Hz,1H),7.457.36(m,1H),5.09(dd,J＝13.3,5.1Hz,1H),4.47(q,J＝16.7Hz,2H),3.44-3.36(m,4H),3.09(d,J＝4.6Hz,4H),2.95-2.85(m,1H),2.81-2.75(m,1H),2.48(qd,J＝13.2,4.7Hz,1H),2.19-2.10(m,1H).LCMS(ESI)C₁₇H₂₁FN₅O₃ ⁺[M+H]⁺： calculated 362.16, found 362.2) was prepared by the method described for the synthesis of scheme Al.

Example A-3 preparation of Compound GT-06988

The title compound GT-06988 (gray solid, 7.9g, yield 97％).¹H NMR(400MHz,DMSO-d6)δ10.96(s,1H),8.74(s,2H),7.73(s,1H),7.36(d,J＝10.7Hz,1H),7.31(d,J＝7.2Hz,1H),5.05(dd,J＝13.3,5.0Hz,1H),4.32(d,J＝16.8Hz,1H),4.20(d,J＝16.9Hz,1H),3.25(s,4H),2.98(s,4H),2.92-2.82(m,1H),2.59(d,J＝17.2Hz,1H),2.36(dd,J＝13.2,4.4Hz,1H),2.04-1.91(m,1H).LCMS(ESI)C₁₇H₂₁FN₅O₃ ⁺[M+H]⁺： calculated 362.16, found 362.2) was prepared according to the method of synthesis scheme A1.

Example A-4 preparation of Compound GT-06989

The title compound GT-06989 (grey solid, 5.4g, yield 87％).¹H NMR(400MHz,MeOD)δ6.77(s,1H),6.65(d,J＝12.1Hz,1H),5.03(dd,J＝13.3,5.1Hz,1H),4.35(q,J＝17.0Hz,2H),3.38(t,J＝4.8Hz,4H),3.02(s,4H),2.85(dd,J＝13.3,5.2Hz,1H),2.792.69(m,1H),2.42(dd,J＝13.1,4.7Hz,1H),2.17-2.07(m,1H).LCMS(ESI)C₁₇H₂₁FN₅O₃ ⁺[M+H]⁺： calculated 362.16, found 362.2) was prepared according to the method of synthesis scheme A1.

Example A-5 preparation of Compound GT-07368

The title compound GT-07368 (grey solid, 5.4g, yield 98％).¹H NMR(400MHz,DMSO-d6)δ10.98(s,1H),8.78(s,2H),7.30(t,J＝7.6Hz,1H),7.17(s,1H),7.08(dd,J＝7.6,4.4Hz,2H),5.09(dd,J＝13.2,5.2Hz,1H),4.36(d,J＝17.6Hz,1H),4.24(d,J＝17.6Hz,1H),3.24(s,4H),2.93(s,4H),2.89(d,J＝5.2Hz,1H),2.62(d,J＝17.2Hz,1H),2.40(qd,J＝13.2,4.4Hz,1H),2.071.97(m,1H).LCMS(ESI)C₁₇H₂₂N₅O₃ ⁺[M+H]⁺： calculated 344.17, found 344.1) was prepared according to the method of synthesis scheme A1.

Example A-6 preparation of Compound GT-05579

The title compound GT-05579 (gray solid, 4.1g, yield 97％).¹H NMR(400MHz,DMSO-d6)δ11.07(s,1H),8.85(s,2H),8.35(s,1H),7.64(d,J＝8.3Hz,1H),7.23(s,1H),7.06(d,J＝7.8Hz,1H),5.05(dd,J＝12.9,5.3Hz,1H),3.68(d,J＝4.3Hz,1H),3.31(d,J＝18.6Hz,4H),2.88(td,J＝14.6,5.2Hz,4H),2.56(dd,J＝20.1,10.7Hz,2H),2.01(dd,J＝9.9,4.8Hz,1H).LCMS(ESI)C₁₇H₂₀N₅O₄ ⁺[M+H]⁺： calculated 358.15, found 358.1) was prepared according to the method of synthesis scheme A1.

Example A-7 preparation of Compound GT-04310

The title compound GT-04310 (pale yellow solid, 1.5g, yield 96％).¹H NMR(400MHz,DMSO-d6)δ11.09(s,1H),8.84(s,1H),8.42(s,1H),7.65(d,J＝10.3Hz,1H),7.57(d,J＝7.0Hz,1H),5.08(dd,J＝12.8,5.4Hz,1H),3.30(s,4H),2.97(d,J＝33.3Hz,4H),2.93-2.83(m,1H),2.56(dd,J＝22.6,11.2Hz,2H),2.05-1.97(m,1H).LCMS(ESI)C₁₇H₁₉FN₅O₄ ⁺[M+H]⁺： calculated 376.14, found 376.2) was prepared according to the method of synthesis scheme B1.

Example A-8 preparation of Compound GT-07007

The title compound GT-07007 (gray solid, 3.6g, yield 92％).¹H NMR(400MHz,DMSO-d6)δ11.09(s,1H),9.48(s,2H),7.74(d,J＝8.5Hz,1H),7.41(d,J＝2.0Hz,1H),7.30(dd,J＝8.5,2.0Hz,1H),5.09(dd,J＝12.9,5.4Hz,1H),3.58(s,4H),3.02(s,4H),2.92-2.83(m,1H),2.57(dd,J＝19.3,10.3Hz,2H),2.08-1.99(m,1H).LCMS(ESI)C₁₇H₂₀N₅O₄ ⁺[M+H]⁺： calculated 358.15, found 358.2) was prepared according to the method of synthesis scheme B2.

Example A-9 preparation of Compound GT-07051

The title compound GT-07051 (gray solid, 1.6g, yield 97％).¹H NMR(400MHz,DMSO-d6)δ10.95(s,1H),9.65(s,2H),7.55(d,J＝8.4Hz,1H),7.13-7.06(m,2H),5.05(dd,J＝13.3,5.1Hz,1H),4.34(d,J＝17.0Hz,1H),4.23(t,J＝17.0Hz,1H),3.46-3.30(m,4H),3.11(brs,4H),2.94-2.84(m,1H),2.58(d,J＝17.2Hz,1H),2.43-2.31(m,1H),1.98-1.90(m,1H).LCMS(ESI)C₁₇H₂₂N₅O₃ ⁺[M+H]⁺： calculated 344.17, found 344.2) was prepared according to the procedure of synthesis scheme B2.

Example A-10 preparation of Compound GT-07008

The target compound GT-07008 was prepared according to the procedure of synthesis scheme C.

Step 1 in a 100ml single-necked flask, (1-aminopiperidin-4-yl) methanol (1.0 eq.) was dissolved in 1, 4-dioxane, and (Boc) ₂ O (1.2 eq.) and triethylamine (3.0 eq.) were added in sequence. The reaction solution was stirred at room temperature for 16 hours. TLC detection reaction was complete. The reaction solution was concentrated under reduced pressure, the resulting concentrate was washed with water, extracted three times with ethyl acetate, the organic phases were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure, and the obtained residue was purified by column chromatography (eluent: petroleum ether: ethyl acetate=0-50%) to give tert-butyl (4- (hydroxymethyl) piperidin-1-yl) carbamate (white solid, yield 80%).

Step 2. In a 100ml single vial, tert-butyl (4- (hydroxymethyl) piperidin-1-yl) carbamate (1.0 eq.) was dissolved in dichloromethane and MsCl (1.2 eq.) and triethylamine (3.0 eq.) were added sequentially. The reaction solution was stirred at room temperature for 1 hour. TLC detection reaction was complete. The reaction solution was washed with water, extracted three times with dichloromethane, the organic phases were combined, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the obtained residue was purified by column chromatography (eluent: petroleum ether: ethyl acetate=0-40%) to give (1- ((t-butoxycarbonyl) amino) piperidin-4-yl) methyl methanesulfonate (white solid, yield 85%).

Step 3 (1- ((t-butoxycarbonyl) amino) piperidin-4-yl) methyl methanesulfonate (1.3 eq.) and 3- (5-mercapto-1-oxoisoindolin-2-yl) piperidine-2, 6-dione (1.0 eq.) were dissolved in dimethyl sulfoxide in a 100ml single-port bottle, and triethylamine (3.0 eq.) was added to the solution. The reaction solution was stirred at room temperature for 16 hours. TLC detection reaction was complete. The reaction solution was washed with water, extracted three times with ethyl acetate, the organic phases were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure, and the obtained residue was purified by column chromatography (eluent: petroleum ether: ethyl acetate=0-50%) to give tert-butyl (4- (((2- (2, 6-dioxopiperidin-3-yl) -1-oxoisoindolin-5-yl) thio) methyl) piperidin-1-yl) carbamate (white solid, yield 50%).

Step 4 to a solution of tert-butyl (4- (((2- (2, 6-dioxopiperidin-3-yl) -1-oxoisoindolin-5-yl) thio) methyl) piperidin-1-yl) carbamate in dichloromethane at room temperature in a 100mL single vial was added trifluoroacetic acid. The reaction was stirred for 1 hour and TLC checked for completion. The reaction solution was concentrated under reduced pressure and lyophilized to give compound GT-07008 (gray solid, 0.6g, yield 93％).¹H NMR(400MHz,MeOD-d4)611.80(s,1H),10.03(s,1H),8.48-8.43(m,1H),8.38(s,1H),8.25(d,J＝7.1Hz,1H),5.91(dd,J＝13.3,5.1Hz,1H),5.17(dd,J＝50.0,17.4Hz,2H),4.26(s,4H),3.86(d,J＝6.1Hz,2H),3.77-3.68(m,1H),3.42(d,J＝17.0Hz,1H),3.30-3.12(m,2H),2.89-2.68(m,3H),2.27-2.16(m,2H).LCMS(ESI)C₁₉H₂₅N₄O₃S⁺[M+H]⁺： calculated 389.16, found 389.2.

Example A-11 preparation of Compound GT-07966

The title compound GT-07966 (yellow solid, 1.56g, calculated yield 94％).¹H NMR(400MHz,DMSO-d6)δ10.93(s,1H),8.99(s,2H),7.56(s,1H),7.46(d,J＝8.4Hz,1H),6.94(s,1H),6.87(d,J＝8.4Hz,1H),5.03(dd,J＝13.2,5.2Hz,1H),4.31(d,J＝16.8Hz,1H),4.18(d,J＝16.8Hz,1H),4.08-4.01(m,2H),2.99-2.82(m,5H),2.58(d,J＝16.8Hz,1H),2.33(dd,J＝13.2,4.4Hz,1H),2.15(d,J＝8.8Hz,2H),1.98-1.89(m,3H).LCMS(ESI)C₁₉H₂₄N₅O₃ ⁺: 370.19; found: 370.1) was prepared according to the method of FIG. A1.

Example A-12 preparation of Compound GT-08008

The title compound GT-08008 (yellow solid, 1.7g, yield 83％).¹H NMR(400MHz,DMSO-d6)δ10.93(s,1H),9.49(s,1H),7.98(s,1H),7.47(d,J＝8.4Hz,2H),7.03(s,1H),6.96(d,J＝8.4Hz,1H),5.03(dd,J＝13.2,5.2Hz,1H),4.30(dd,J＝11.2,5.6Hz,3H),4.18(d,J＝16.8Hz,1H),3.46(d,J＝10.4Hz,2H),3.34(d,J＝11.2Hz,2H),2.96-2.85(m,1H),2.75-2.64(m,1H),2.58(d,J＝16.8Hz,1H),2.35(ddd,J＝26.0,13.2,4.4Hz,2H),1.98-1.91(m,1H).LCMS(ESI)C₁₈H₂₂N₅O₃ ⁺ calculated: 356.16; found: 356.1) was prepared by the method described in connection with scheme A1.

Example A-13 preparation of Compound GT-08009

The title compound GT-08009 (yellow solid, 1.2g, yield 75％).¹H NMR(400MHz,DMSO-d6)δ10.93(s,1H),9.03(s,1H),8.77(s,1H),7.72(s,1H),7.45(d,J＝8.4Hz,1H),6.96(s,1H),6.86(d,J＝8.4Hz,1H),5.03(dd,J＝13.2,5.2Hz,1H),4.30(d,J＝16.4Hz,2H),4.17(d,J＝16.8Hz,1H),3.63(s,1H),3.15(s,2H),3.07-2.77(m,2H),2.58(d,J＝16.8Hz,1H),2.39-2.14(m,2H),1.95(dd,J＝9.2,3.6Hz,1H),1.75(d,J＝10.8Hz,1H),0.83(dd,J＝9.6,6.8Hz,1H).LCMS(ESI)C₁₈H₂₂N₅O₃ ⁺ calculated: 356.17; found: 356.1) was prepared according to the procedure of synthesis scheme A1.

Example A-14 preparation of Compound GT-08007

The title compound GT-08007 (brown solid, 1.1g, yield 99％).¹H NMR(400MHz,DMSO-d6)δ10.94(s,1H),8.91(s,2H),7.73(s,1H),7.45(d,J＝8.4Hz,1H),6.96(s,1H),6.87(d,J＝8.4Hz,1H),5.03(dd,J＝13.2,5.2Hz,1H),4.31(d,J＝16.8Hz,1H),4.18(d,J＝16.8Hz,1H),3.26(d,J＝4.8Hz,4H),3.12(s,2H),2.91(ddd,J＝18.4,13.6,6.4Hz,3H),2.59(d,J＝16.8Hz,1H),2.35(qd,J＝13.2,4.4Hz,1H),2.04-1.82(m,3H).LCMS(ESI).C₁₈H₂₄N₅O₃ ⁺[M+H]⁺： calculated, 358.18; found, 358.2) was prepared by the method described in connection with scheme A1.

Examples A-15 preparation of Compound GT-08006

The title compound GT-08006 (brown solid, 980mg, yield 95％).¹H NMR(400MHz,DMSO-d6)δ10.99(s,1H),9.02(s,2H),7.49(d,J＝8.4Hz,1H),7.28(d,J＝16.8Hz,1H),6.94(s,1H),6.88(d,J＝8.4Hz,1H),5.08(dd,J＝13.2,5.2Hz,1H),4.35(d,J＝16.8Hz,1H),4.21(d,J＝16.8Hz,1H),3.80(t,J＝6.0Hz,4H),3.01-2.90(m,1H),2.64(d,J＝16.8Hz,5H),2.39(ddd,J＝26.0,13.2,4.4Hz,1H),1.99(dd,J＝17.6,10.4Hz,5H).LCMS(ESI)C₂₀H₂₆N₅O₃ ⁺[M+H]⁺： calculated, 384.20; found, 384.3) was prepared by the method of scheme A1.

Example A-16 preparation of Compound GT-07965

The title compound GT-07965 (off-white solid, 1.1g, yield 99％).¹H NMR(400MHz,DMSO-d6)δ10.94(s,1H),8.93(s,1H),8.76(s,1H),7.44(d,J＝8.4Hz,1H),7.24(s,1H),6.95(s,1H),6.89(d,J＝8.0Hz,1H),5.03(dd,J＝13.2,4.8Hz,1H),4.29(d,J＝16.8Hz,1H),4.19(s,1H),3.47(s,2H),3.10-2.82(m,7H),2.68(s,2H),2.59(d,J＝17.6Hz,1H),2.34(dt,J＝22.4,11.2Hz,1H),2.02-1.90(m,1H).LCMS(ESI)C₁₉H₂₄N₅O₃ ⁺[M+H]⁺： calculated, 370.18; found, 370.1) was prepared according to the method of synthesis scheme A1.

EXAMPLE 1 preparation of Compound GT-06422

The title compound GT-06422 (white solid, 15mg, yield 25％).¹H NMR(400MHz,DMSO-d6)δ11.66(s,1H),11.07(s,1H),7.95-7.79(m,3H),7.63(d,J＝8.2Hz,1H),7.54-7.30(m,7H),7.23-7.19(m,1H),7.08-6.96(m,1H),5.05(dd,J＝12.6,5.3Hz,1H),3.30-3.15(m,6H),3.15-3.01(m,2H),2.96-2.78(m,2H),2.58(d,J＝17.6Hz,1H),2.45-2.33(m,1H),2.05-1.95(m,1H).LCMS(ESI)C₃₀H₃₀N₅O₄ ⁺[M+H]⁺： calculated 524.23, found 524.3) was prepared according to the procedure of FIG. 2.

EXAMPLE 2 preparation of Compound GT-06401

The title compound GT-06401 (white solid, 10mg, yield 16％).¹H NMR(400MHz,DMSO-d6)δ10.99(s,1H),7.87-7.73(m,1H),7.68-7.53(m,2H),7.48-7.39(m,2H),7.36-7.23(m,2H),7.22-7.05(m,3H),6.97-6.93(m,1H),4.97(dd,J＝12.7,5.5Hz,1H),3.21-3.11(m,4H),3.11-2.91(m,4H),2.80-2.76(m,2H),2.53-2.48(m,1H),2.41-2.33(m,1H),1.99-1.87(m,1H).LCMS(ESI)C₃₀H₂₈F₂N₅O₄ ⁺[M+H]⁺： calculated 560.21, found 560.2) was prepared according to the procedure of FIG. 2.

EXAMPLE 3 preparation of Compound GT-06509

The title compound GT-06509 (white solid, 41mg, yield 66％).¹H NMR(400MHz,DMSO-d6)δ11.00(s,1H),9.69(s,1H),8.30(s,1H),7.54(d,J＝8.3Hz,1H),7.19-7.12(m,4H),6.95(d,J＝7.6Hz,1H),4.97(dd,J＝12.7,5.3Hz,1H),3.61-3.48(m,2H),3.05-2.73(m,8H),2.51(d,J＝18.1Hz,1H),2.48-2.46(m,1H),2.20(brs,5H),1.99-1.86(m,1H),1.64(brs,4H).LCMS(ESI)C₃₀H₃₃FN₅O₄ ⁺[M+H]⁺： calculated 546.25, found 546.3) was prepared according to the procedure of scheme 2.

EXAMPLE 4 preparation of Compound GT-07045

The title compound GT-07045 (white solid, 34mg, yield 53％).¹H NMR(400MHz,DMSO-d6)δ10.99(s,1H),10.17(s,1H),8.32(s,1H),7.54(d,J＝8.3Hz,1H),7.43(d,J＝8.2Hz,2H),7.19(d,J＝8.3Hz,2H),7.12(s,1H),6.95(s,1H),4.97(dd,J＝12.8,5.4Hz,1H),4.30(s,2H),3.76(t,J＝5.3Hz,2H),3.61(s,2H),3.39-3.31(m,2H),3.07-3.01(m,2H),2.98-2.85(m,4H),2.81-2.76(m,1H),2.49-2.43(m,2H),2.30(s,2H),1.96-1.89(m,1H).LCMS(ESI)C₂₉H₃₁ClN₅O₅ ⁺[M+H]⁺： calculated 564.20, found 564.2) was prepared according to the procedure of scheme 1.

EXAMPLE 5 preparation of Compound GT-06423

The title compound GT-06423 (white solid, 14mg, yield 24％).¹H NMR(400MHz,DMSO-d6)δ11.37(s,1H),11.09(s,1H),7.94-7.74(m,3H),7.64(d,J＝10.2Hz,1H),7.60-7.26(m,8H),5.07(dd,J＝12.9,5.3Hz,1H),3.31-3.17(m,6H),3.13-3.06(m,2H),2.94-2.83(m,2H),2.59(d,J＝19.6Hz,1H),2.49-2.42(m,1H),2.07-1.96(m,1H).LCMS(ESI)C₃₀H₂₉FN₅O₄ ⁺[M+H]⁺： calculated 542.22, found 542.3) was prepared according to the procedure of scheme 2.

EXAMPLE 6 preparation of Compound GT-06402

The title compound GT-06402 (white solid, 14mg, yield 22％).¹H NMR(400MHz,DMSO-d6)δ11.09(s,1H),7.96-7.78(m,1H),7.64(d,J＝10.3Hz,2H),7.59-7.41(m,4H),7.34-7.01(m,3H),5.07(dd,J＝12.6,5.4Hz,1H),3.29-3.17(m,4H),3.17-2.95(m,4H),2.95-2.81(m,2H),2.61-2.56(m,2H),2.49-2.38(m,1H),2.06-1.94(m,1H).LCMS(ESI)C₃₀H₂₇F₃N₅O₄ ⁺[M+H]⁺： calculated 578.20, found 578.2) was prepared according to the procedure of scheme 2.

EXAMPLE 7 preparation of Compound GT-06510

The title compound GT-06510 (white solid, 41mg, yield 67％).¹H NMR(400MHz,DMSO-d6)δ11.08(s,1H),9.68(s,1H),8.41(s,1H),7.64(d,J＝10.3Hz,1H),7.52(d,J＝6.9Hz,1H),7.27-7.20(m,3H),5.06(dd,J＝12.8,5.4Hz,1H),3.65-3.58(m,2H),3.21-3.13(m,2H),3.10-3.05(m,1H),3.04-2.78(m,6H),2.58(d,J＝19.8Hz,1H),2.39-2.20(m,5H),2.06-1.96(m,1H),1.71(brs,4H).LCMS(ESI)C₃₀H₃₂F₂N₅O₄ ⁺[M+H]⁺： calculated 564.24, found 564.3) was prepared according to the procedure of FIG. 2.

EXAMPLE 8 preparation of Compound GT-06961

The title compound GT-06961 (white solid, 15mg, yield 24％).¹H NMR(400MHz,DMSO-d6)δ11.01(s,1H),9.89(s,1H),8.34(s,1H),7.56(d,J＝10.3Hz,1H),7.43(d,J＝7.7Hz,3H),7.19(d,J＝8.2Hz,2H),4.99(dd,J＝12.8,5.4Hz,1H),4.27(s,2H),3.77(t,J＝5.1Hz,2H),3.62(s,2H),3.44-3.38(m,2H),3.16-3.03(m,2H),3.03-2.84(m,4H),2.83-2.77(m,1H),2.53-2.46(m,2H),2.30(s,2H),2.00-1.86(m,1H).LCMS(ESI)C₂₉H₃₀ClFN₅O₅ ⁺[M+H]⁺： calculated 582.19, found 582.2) was prepared according to the procedure of scheme 1.

EXAMPLE 9 preparation of Compound GT-06398

The title compound GT-06398 (white solid, 14mg, yield 22％).¹H NMR(400MHz,DMSO-d6)δ10.86(s,1H),7.88-7.78(m,1H),7.70-7.59(m,2H),7.53-7.41(m,2H),7.38(d,J＝8.4Hz,1H),7.35-7.26(m,1H),7.24-7.10(m,2H),6.85(s,1H),6.79(d,J＝8.6Hz,1H),4.95(dd,J＝13.2,5.2Hz,1H),4.22(d,J＝16.9Hz,1H),4.09(d,J＝16.9Hz,1H),3.24-3.09(m,4H),3.06-2.93(m,2H),2.87-2.85(m,3H),2.66(s,1H),2.51(d,J＝17.8Hz,1H),2.32-2.22(m,1H),1.95-1.81(m,1H).LCMS(ESI)C₃₀H₃₀F₂N₅O₃ ⁺[M+H]⁺： calculated 546.23, found 546.2) was prepared according to the procedure of scheme 2.

EXAMPLE 10 preparation of Compound GT-06426

The title compound GT-06426 (white solid, 18mg, yield 28％).¹H NMR(400MHz,DMSO-d6)δ10.86(s,1H),7.96-7.75(m,3H),7.66-7.58(m,1H),7.38(d,J＝8.1Hz,1H),7.33-7.14(m,4H),6.85(s,1H),6.82-6.72(m,1H),4.95(dd,J＝13.3,5.1Hz,1H),4.22(d,J＝17.0Hz,1H),4.09(d,J＝16.9Hz,1H),3.19-3.08(m,4H),3.07-2.95(m,4H),2.87-2.77(m,2H),2.51(d,J＝17.2Hz,1H),2.32-2.22(m,1H),1.96-1.80(m,1H).LCMS(ESI)C₃₀H₃₀F₂N₅O₃ ⁺[M+H]⁺： calculated 546.23, found 546.2) was prepared according to the procedure of scheme 2.

EXAMPLE 11 preparation of Compound GT-06427

The title compound GT-06427 (white solid, 23mg, yield 34％).¹H NMR(400MHz,DMSO-d6)δ10.86(s,1H),7.91-7.74(m,2H),7.58-7.27(m,7H),6.84(s,1H),6.78(d,J＝7.7Hz,1H),4.95(dd,J＝13.4,5.0Hz,1H),4.22(d,J＝16.7Hz,1H),4.09(d,J＝17.0Hz,1H),3.20-3.12(m,4H),3.04-2.92(m,4H),2.89-2.77(m,2H),2.51(d,J＝17.6Hz,1H),2.31-2.22(m,1H),1.91-1.84(m,1H).LCMS(ESI)C₃₀H₃₀Cl₂N₅O₃ ⁺[M+H]⁺： calculated 578.17, found 578.2) was prepared according to the procedure of scheme 2.

EXAMPLE 12 preparation of Compound GT-06428

The title compound GT-06428 (white solid, 23mg, yield 35％).¹H NMR(400MHz,DMSO-d6)δ11.12(s,1H),10.86(s,1H),7.66(d,J＝8.4Hz,4H),7.39(d,J＝8.2Hz,1H),6.94(d,J＝8.4Hz,4H),6.86(s,1H),6.79(d,J＝8.6Hz,1H),5.40(d,J＝9.4Hz,1H),4.96(dd,J＝13.2,5.2Hz,1H),4.22(d,J＝16.9Hz,1H),4.09(d,J＝17.0Hz,1H),3.68(s,6H),3.19-3.09(m,4H),3.01(s,4H),2.87-2.80(m,1H),2.51(d,J＝17.4Hz,1H),2.31-2.25(m,1H),1.95-1.79(m,1H).LCMS(ESI)C₃₂H₃₅N₅NaO₅ ⁺[M+Na]⁺： calculated 592.25, found 592.3) was prepared according to the procedure of scheme 2.

EXAMPLE 13 preparation of Compound GT-06499

The title compound GT-06499 (white solid, 29mg, yield 46％).¹H NMR(400MHz,DMSO-d6)δ10.87(s,1H),10.62(s,1H),7.91(s,1H),7.74-7.70(m,2H),7.60(s,1H),7.50(d,J＝8.6Hz,4H),7.40(d,J＝8.3Hz,1H),6.86(s,1H),6.79(d,J＝8.3Hz,1H),4.96(dd,J＝13.2,5.1Hz,1H),4.35(d,J＝3.8Hz,2H),4.23(d,J＝16.9Hz,1H),4.10(d,J＝17.0Hz,1H),3.26-3.22(m,4H),3.10-3.03(m,2H),2.95-2.78(m,3H),2.52(d,J＝16.4Hz,1H),2.32-3.23(m,1H),1.92-1.87(m,1H).LCMS(ESI)C₃₀H₃₁ClN₅O₃ ⁺[M+H]⁺： calculated 544.21, found 544.2) was prepared according to the procedure of scheme 1.

EXAMPLE 14 preparation of Compound GT-06500

The title compound GT-06500 (white solid, 32mg, yield 51％).¹H NMR(400MHz,DMSO-d6)δ10.87(s,1H),10.57(s,1H),7.74-7.67(m,4H),7.63(d,J＝8.0Hz,2H),7.48(d,J＝8.6Hz,2H),7.40(d,J＝8.4Hz,1H),6.86(s,1H),6.80(d,J＝8.3Hz,1H),4.96(dd,J＝13.3,5.0Hz,1H),4.32(brs,2H),4.23(d,J＝17.0Hz,1H),4.10(d,J＝17.0Hz,1H),3.27-3.16(m,4H),3.10-3.00(m,2H),2.94-2.77(m,3H),2.52(d,J＝17.3Hz,1H),2.34-2.21(m,1H),1.94-1.83(m,1H).LCMS(ESI)C₃₀H₃₁ClN₅O₃ ⁺[M+H]⁺： calculated 544.21, found 544.2) was prepared according to the procedure of scheme 1.

EXAMPLE 15 preparation of Compound GT-06505

The title compound GT-06505 (white solid, 20mg, yield 32％).¹H NMR(400MHz,DMSO-d6)δ10.94(s,1H),7.44(d,J＝8.4Hz,1H),7.24-7.16(m,4H),6.90(s,1H),6.84(d,J＝8.2Hz,1H),5.02(dd,J＝13.3,5.2Hz,1H),4.28(d,J＝16.9Hz,1H),4.15(d,J＝16.9Hz,1H),2.94-2.82(m,5H),2.59(d,J＝17.4Hz,1H),2.32-2.25(m,7H),1.98-1.93(m,1H),1.71-1.64(m,8H).LCMS(ESI)C₃₀H₃₅FN₅O₃ ⁺[M+H]⁺： calculated 532.27, found 532.3) was prepared according to the procedure of scheme 2.

EXAMPLE 16 preparation of Compound GT-06501

The title compound GT-06501 (white solid, 12mg, yield 19％).¹H NMR(400MHz,DMSO-d6)δ10.93(s,1H),10.26(s,1H),7.44(d,J＝8.3Hz,1H),7.35-7.21(m,4H),6.89(s,1H),6.83(d,J＝8.9Hz,1H),5.02(dd,J＝13.2,4.7Hz,1H),4.37(s,2H),4.28(d,J＝16.8Hz,1H),4.14(d,J＝16.8Hz,1H),3.84(t,J＝5.1Hz,2H),3.65(s,2H),3.05-2.83(m,7H),2.61-2.54(m,2H),2.44-2.29(m,4H),2.01-1.88(m,1H).LCMS(ESI)C₂₉H₃₃FN₅O₄ ⁺[M+H]⁺： calculated 534.25, found 534.3) was prepared according to the procedure of scheme 1.

EXAMPLE 17 preparation of Compound GT-06511

The title compound GT-06511 (white solid, 22mg, yield 34％).¹H NMR(400MHz,DMSO-d6)δ10.93(s,1H),10.18(s,1H),7.51(d,J＝8.4Hz,2H),7.44(d,J＝8.4Hz,1H),7.27(d,J＝8.4Hz,2H),6.90(s,1H),6.84(d,J＝8.0Hz,1H),5.02(dd,J＝13.2,5.0Hz,1H),4.36(s,2H),4.28(d,J＝16.8Hz,1H),4.14(d,J＝16.9Hz,1H),3.84(t,J＝5.4Hz,2H),3.72-3.62(m,2H),3.17-2.76(m,8H),2.58(d,J＝18.9Hz,1H),2.56-2.53(m,1H),2.41-2.33(m,3H),1.99-1.93(m,1H).LCMS(ESI)C₂₉H₃₃ClN₅O₄ ⁺[M+H]⁺： calculated 550.22, found 550.3) was prepared according to the procedure of scheme 1.

EXAMPLE 18 preparation of Compound GT-06502

The title compound GT-06502 (white solid, 19mg, yield 28％).¹H NMR(400MHz,DMSO-d6)δ10.93(s,1H),10.20(s,1H),7.50(d,J＝8.4Hz,2H),7.44(d,J＝8.4Hz,1H),7.25(d,J＝8.4Hz,2H),6.90(s,1H),6.84(d,J＝8.4Hz,1H),5.02(dd,J＝13.3,5.0Hz,1H),4.37(s,2H),4.28(d,J＝17.0Hz,1H),4.14(d,J＝16.9Hz,1H),3.67(brs,2H),3.06-2.83(m,7H),2.64-2.52(m,3H),2.35-2.32(m,1H),2.24(s,2H),2.00-1.88(m,1H),1.23(s,6H).LCMS(ESI)C₃₁H₃₇ClN₅O₄ ⁺[M+H]⁺： calculated 578.25, found 578.3) was prepared according to the procedure of scheme 1.

EXAMPLE 19 preparation of Compound GT-06420

The title compound GT-06420 (white solid, 18mg, yield 30％).¹H NMR(400MHz,DMSO-d6)δ11.29(s,1H),10.89(s,1H),7.80-7.73(m,2H),7.48-7.38(m,4H),7.37-7.29(m,4H),7.27-7.13(m,2H),5.55(s,1H),4.97(dd,J＝13.3,4.9Hz,1H),4.38(d,J＝16.9Hz,1H),4.20(d,J＝16.7Hz,1H),3.53-3.44(m,1H),3.18-3.07(m,4H),3.04-2.98(m,2H),2.87-2.78(m,2H),2.52(d,J＝18.1Hz,1H),2.34-2.26(m,1H),1.93-1.85(m,1H).LCMS(ESI)C₃₀H₃₁FN₅O₃ ⁺[M+H]⁺： calculated 528.24, found 528.3) was prepared according to the procedure of scheme 1.

EXAMPLE 20 preparation of Compound GT-06399

The title compound GT-06399 (white solid, 11mg, yield 17％).¹H NMR(400MHz,DMSO-d6)δ10.89(s,1H),7.83-7.72(m,1H),7.70-7.51(m,2H),7.51-7.38(m,2H),7.36-7.28(m,2H),7.26-7.05(m,3H),4.97(dd,J＝13.2,4.9Hz,1H),4.38(d,J＝16.8Hz,1H),4.20(d,J＝16.7Hz,1H),3.22-3.10(m,4H),3.07-2.98(m,2H),2.88-2.75(m,3H),2.66(s,1H),2.51(d,J＝17.5Hz,1H),2.36-2.24(m,1H),1.94-1.83(m,1H).LCMS(ESI)C₃₀H₂₉F₃N₅O₃ ⁺[M+H]⁺： calculated 564.22, found 564.2) was prepared according to the procedure described in scheme 1.

EXAMPLE 21 preparation of Compound GT-06506

The title compound GT-06506 (white solid, 13mg, yield 22％).¹H NMR(400MHz,DMSO-d6)δ10.89(s,1H),9.50(s,1H),7.64(s,1H),7.31(d,J＝8.2Hz,1H),7.19-7.13(m,4H),4.97(dd,J＝13.2,5.1Hz,1H),4.38(d,J＝16.7Hz,1H),4.20(d,J＝16.8Hz,1H),3.56-3.48(m,2H),3.07-2.95(m,4H),2.92-2.82(m,4H),2.52(d,J＝17.4Hz,1H),2.38-2.24(m,2H),2.19(brs,4H),1.92-1.83(m,1H),1.64(brs,4H).LCMS(ESI)C₃₀H₃₄F₂N₅O₃ ⁺[M+H]⁺： calculated 550.26, found 550.3) was prepared according to the procedure of scheme 2.

EXAMPLE 22 preparation of Compound GT-06507

The title compound GT-06507 (white solid, 33mg, yield 54％).¹H NMR(400MHz,DMSO-d6)δ10.95(s,1H),9.90(s,1H),7.72(s,1H),7.34(d,J＝10.7Hz,1H),7.24(d,J＝8.5Hz,4H),5.03(dd,J＝13.2,5.1Hz,1H),4.29(d,J＝16.9Hz,1H),4.16(d,J＝16.9Hz,1H),3.63-3.58(m,2H),3.15-2.95m,3H),2.94-2.86(m,5H),2.59(d,J＝16.8Hz,1H),2.35-2.21(m,6H),1.97-1.93(m,1H),1.71(brs,4H).LCMS(ESI)C₃₀H₃₄F₂N₅O₃ ⁺[M+H]⁺： calculated 550.26, found 550.3) was prepared according to the procedure of scheme 2.

EXAMPLE 23 preparation of Compound GT-06421

The title compound GT-06421 (white solid, 12mg, yield 20％).¹H NMR(400MHz,DMSO-d6)δ11.61(s,1H),10.95(s,1H),8.13-7.98(m,1H),7.97-7.81(m,3H),7.51-7.38(m,6H),6.74-6.65(m,1H),6.62-6.58(m,1H),4.98(dd,J＝13.3,5.1Hz,1H),4.31(d,J＝17.3Hz,1H),4.17(d,J＝16.9Hz,1H),3.60-3.52(m,1H),3.26-3.14(m,4H),3.11-3.05(m,3H),2.97-2.80(m,2H),2.58(d,J＝17.7Hz,1H),2.34-2.29(m,1H),2.00-1.89(m,1H).LCMS(ESI)C₃₀H₃₁FN₅O₃ ⁺[M+H]⁺： calculated 528.24, found 528.2) was prepared according to the procedure of scheme 2.

EXAMPLE 24 preparation of Compound GT-06400

The title compound GT-06400 (white solid, 24mg, yield 38％).¹H NMR(400MHz,DMSO-d6)δ10.95(s,1H),8.17-8.13(m,1H),7.94-7.79(m,1H),7.77-7.62(m,1H),7.59-7.35(m,4H),7.31-7.12(m,2H),6.68(s,1H),6.65-6.50(m,1H),4.98(dd,J＝13.2,5.0Hz,1H),4.31(d,J＝17.2Hz,1H),4.17(d,J＝16.9Hz,1H),3.28-3.17(m,4H),3.13-3.04(m,2H),2.94-2.84(m,3H),2.74(s,1H),2.58(d,J＝16.3Hz,1H),2.36-2.25(m,1H),2.01-1.88(m,1H).LCMS(ESI)C₃₀H₂₉F₃N₅O₃ ⁺[M+H]⁺： calculated 564.22, found 564.3) was prepared according to the procedure of scheme 2.

EXAMPLE 25 preparation of Compound GT-06508

The title compound GT-06508 (white solid, 38mg, yield 62％).¹H NMR(400MHz,DMSO-d6)δ10.87(s,1H),10.19(s,1H),7.97(s,1H),7.16(dd,J＝13.1,4.4Hz,3H),6.59(s,1H),6.52(d,J＝12.1Hz,1H),4.91(dd,J＝13.3,5.1Hz,1H),4.22(d,J＝17.3Hz,1H),4.08(d,J＝17.3Hz,1H),3.54-3.45(m,2H),3.13-2.95(m,3H),2.91-2.73(m,5H),2.56-2.46(m,1H),2.36-2.12(m,6H),1.96-1.82(m,1H),1.63(s,4H).LCMS(ESI)C₃₀H₃₄F₂N₅O₃ ⁺[M+H]⁺： calculated 550.26, found 550.3) was prepared according to the procedure of scheme 2.

EXAMPLE 26 preparation of Compound GT-06863

The title compound GT-06863 (white solid, 25mg, yield 36％).¹H NMR(400MHz,DMSO-d6)δ10.86(s,1H),7.38(d,J＝8.4Hz,1H),7.26(d,J＝4.4Hz,2H),7.14-7.05(m,1H),6.87(s,1H),6.79(d,J＝8.1Hz,1H),4.96(dd,J＝13.2,5.0Hz,1H),4.24(d,J＝16.9Hz,1H),4.10(d,J＝16.9Hz,1H),3.34-3.14(m,9H),2.98-2.87(m,4H),2.88-2.77(m,1H),2.70-2.61(m,3H),2.52(d,J＝16.8Hz,1H),2.34-2.21(m,1H),1.92-1.87(m,1H).LCMS(ESI)C₂₈H₃₂Cl₂N₇O₄ ⁺[M+H]⁺： calculated 600.19, found 600.2) was prepared according to the procedure of scheme 4.

EXAMPLE 27 preparation of Compound GT-06864

The title compound GT-06864 (white solid, 26mg, yield 41％).¹H NMR(400MHz,DMSO-d6)δ10.87(s,1H),7.39(d,J＝8.4Hz,1H),7.29(s,2H),7.14(t,J＝8.7Hz,2H),6.91(s,1H),6.83(d,J＝8.1Hz,1H),4.96(dd,J＝13.2,5.1Hz,1H),4.30-4.09(m,5H),3.39(brs.4H),3.32-3.26(m,2H),3.20(brs,4H),2.90-2.78(m,1H),2.75-2.66(m,3H),2.52(d,J＝16.9Hz,1H),2.35-2.21(m,1H),1.91-1.87(m,1H).LCMS(ESI)C₂₈H₃₃FN₇O₄ ⁺[M+H]⁺： calculated 550.26, found 550.3) was prepared according to the procedure of scheme 4.

EXAMPLE 28 preparation of Compound GT-06865

The title compound GT-06865 (white solid, 35mg, yield 53％).¹H NMR(400MHz,DMSO-d6)δ10.87(s,1H),7.39(d,J＝8.3Hz,1H),7.22(d,J＝8.9Hz,2H),6.99(d,J＝8.9Hz,2H),6.90(s,1H),6.82(d,J＝8.3Hz,1H),4.96(dd,J＝13.3,5.1Hz,1H),4.27-4.01(m,5H),3.33-3.23(m,6H),3.12(brs,4H),2.90-2.77(m,1H),2.76-2.60(m,3H),2.52(d,J＝16.8Hz,1H),2.33-2.24(m,1H),1.97-1.87(m,1H).LCMS(ESI)C₂₈H₃₃ClN₇O₄ ⁺[M+H]⁺： calculated 566.23, found 566.2) was prepared according to the procedure of scheme 4.

EXAMPLE 29 preparation of Compound GT-06866

The title compound GT-06866 (white solid, 36mg, yield 51％).¹H NMR(400MHz,DMSO-d6)δ10.94(s,1H),7.47(d,J＝8.3Hz,1H),7.42(d,J＝8.8Hz,2H),7.03(d,J＝8.8Hz,2H),7.00(s,1H),6.91(d,J＝8.0Hz,1H),5.03(dd,J＝13.2,5.0Hz,1H),4.34-4.20(m,5H),3.36(brs,6H),3.20(brs,4H),2.99-2.88(m,1H),2.86-2.71(m,3H),2.59(d,J＝17.5Hz,1H),2.41-2.33(m,1H),1.98-1.90(m,1H).LCMS(ESI)C₂₈H₃₃BrN₇O₄ ⁺[M+H]⁺： calculated 610.18, found 610.2) was prepared according to the procedure of scheme 4.

EXAMPLE 30 preparation of Compound GT-06867

The title compound GT-06867 (white solid, 25mg, yield 38％).¹H NMR(400MHz,DMSO-d6)δ10.94(s,1H),7.46(d,J＝8.3Hz,1H),7.14-7.08(m,1H),7.04-6.98(m,2H),6.90-6.86(m,2H),5.03(dd,J＝13.3,5.1Hz,1H),4.37-4.19(m,5H),3.35(brs,6H),3.06(brs,4H),2.97-2.85(m,1H),2.81-2.72(m,3H),2.59(d,J＝16.6Hz,1H),2.39-2.32(m,1H),1.99-1.90(m,1H).LCMS(ESI)C₂₈H₃₂F₂N₇O₄ ⁺[M+H]⁺： calculated 568.25, found 568.3) was prepared according to the procedure of scheme 4.

EXAMPLE 31 preparation of Compound GT-06868

The title compound GT-06868 (white solid, 15mg, yield 24％).¹H NMR(400MHz,DMSO-d6)δ10.86(s,1H),7.38(d,J＝8.4Hz,1H),7.22(dd,J＝8.4,5.7Hz,2H),7.04(t,J＝8.8Hz,2H),6.86(s,1H),6.78(d,J＝8.4Hz,1H),4.96(dd,J＝13.3,5.0Hz,1H),4.24(d,J＝16.8Hz,1H),4.10(d,J＝16.9Hz,1H),3.65(d,J＝12.7Hz,2H),3.27-3.15(m,5H),2.90-2.72(m,4H),2.69-2.61(m,4H),2.52(d,J＝16.6Hz,1H),2.33-2.20(m,1H),1.93-1.82(m,1H),1.70-1.67(m,2H),1.54-1.45(m,2H).LCMS(ESI)C₂₉H₃₄FN₆O₄ ⁺[M+H]⁺： calculated 549.26, found 549.3) was prepared according to the method of FIG. 4.

EXAMPLE 32 preparation of Compound GT-06869

The title compound GT-06869 (white solid, 18mg, yield 26％).¹H NMR(400MHz,DMSO-d6)δ10.86(s,1H),7.44(dd,J＝7.7,1.6Hz,1H),7.38(d,J＝8.3Hz,1H),7.35-7.26(m,2H),6.86(s,1H),6.78(d,J＝8.1Hz,1H),4.96(dd,J＝13.2,5.0Hz,1H),4.24(d,J＝16.9Hz,1H),4.10(d,J＝16.9Hz,1H),3.68(d,J＝13.2Hz,2H),3.27-3.19(m,5H),3.11(t,J＝12.0Hz,2H),2.86-2.78(m,3H),2.80-2.62(m,3H),2.52(d,J＝16.7Hz,1H),2.32-2.22(m,1H),1.91-1.84(m,1H),1.72-1.69(m,2H),1.57-1.49(m,2H).LCMS(ESI)C₂₉H₃₃Cl₂N₆O₄ ⁺[M+H]⁺： calculated 599.19, found 599.2) was prepared according to the procedure of scheme 4.

EXAMPLE 33 preparation of Compound GT-06870

The title compound GT-06870 (white solid, 19mg, yield 28％).¹H NMR(400MHz,DMSO-d6)δ10.86(s,1H),7.38(d,J＝8.4Hz,1H),7.34-7.25(m,1H),7.24-7.15(m,2H),6.86(s,1H),6.78(d,J＝8.3Hz,1H),4.95(dd,J＝13.3,5.1Hz,1H),4.24(d,J＝17.0Hz,1H),4.10(d,J＝17.0Hz,1H),3.68(d,J＝13.1Hz,2H),3.35-3.14(m,5H),3.07(t,J＝12.0Hz,1H),2.87-2.77(m,3H),2.72-2.61(m,3H),2.51(d,J＝16.6Hz,1H),2.32-2.22(m,1H),1.92-1.86(m,1H),1.71-1.68(m,2H),1.58-1.50(m,2H).LCMS(ESI)C₂₉H₃₃ClFN₆O₄ ⁺[M+H]⁺： calculated 583.22, found 583.3) was prepared according to the method of scheme 4.

EXAMPLE 34 preparation of Compound GT-06871

The title compound GT-06871 (white solid, 22mg, yield 33％).¹H NMR(400MHz,DMSO-d6)δ10.86(s,1H),7.38(d,J＝8.3Hz,1H),7.23-7.18(m,1H),7.14-7.08(m,2H),6.86(s,1H),6.78(d,J＝8.3Hz,1H),4.96(dd,J＝13.3,5.1Hz,1H),4.24(d,J＝16.9Hz,1H),4.10(d,J＝16.9Hz,1H),3.66(d,J＝12.9Hz,2H),3.25-3.16(m,4H),3.00-2.95(m,1H),2.88-2.78(m,4H),2.69-2.61(m,3H),2.52(d,J＝17.0Hz,1H),2.32-2.22(m,1H),1.93-1.86(m,1H),1.73-1.66(m,2H),1.63-1.54(m,2H).LCMS(ESI)C₂₉H₃₃F₂N₆O₄ ⁺[M+H]⁺： calculated 567.25, found 567.3) was prepared according to the procedure of scheme 4.

EXAMPLE 35 preparation of Compound GT-06436

The title compound GT-06436 (pale yellow solid, 43mg, yield 64％).¹H NMR(400MHz,DMSO-d6)δ11.08(s,1H),9.37(s,1H),8.98(s,1H),8.21(dd,J＝7.9,1.6Hz,2H),7.67-7.55(m,4H),7.25(s,1H),7.06(s,1H),5.06(dd,J＝12.9,5.3Hz,1H),4.65(d,J＝28.9Hz,2H),3.51(d,J＝33.9Hz,4H),3.38(s,1H),3.10(d,J＝31.6Hz,4H),2.88(dd,J＝10.1,7.0Hz,1H),2.59(d,J＝17.2Hz,1H),2.54(d,J＝4.5Hz,1H),2.09-1.95(m,1H).LCMS(ESI)C₂₈H₂₈N₇O₄ ⁺[M+H]⁺： calculated 526.22, found 526.2) was prepared according to the procedure of scheme 2.

EXAMPLE 36 preparation of Compound GT-06437

The title compound GT-06437 (pale yellow solid, 37mg, yield 53％).¹H NMR(400MHz,DMSO-d6)δ11.09(s,1H),10.94(s,1H),9.37(s,1H),8.97(s,1H),8.21(dd,J＝7.9,1.6Hz,2H),7.66(d,J＝10.3Hz,1H),7.58(d,J＝7.4Hz,3H),5.08(dd,J＝12.8,5.4Hz,1H),4.65(d,J＝30.2Hz,2H),3.55(s,6H),3.14(s,4H),2.99-2.80(m,1H),2.59(d,J＝18.0Hz,1H),2.09-1.96(m,1H).LCMS(ESI)C₂₈H₂₇FN₇O₄ ⁺[M+H]⁺： calculated 544.21, found 544.3) was prepared according to the method of scheme 2.

EXAMPLE 37 preparation of Compound GT-06438

The title compound GT-06438 (grey solid, 42mg, yield 62％).¹H NMR(400MHz,DMSO-d6)δ11.03(d,J＝59.2Hz,2H),9.37(d,J＝1.3Hz,1H),8.98(d,J＝1.1Hz,1H),8.22(dd,J＝7.9,1.6Hz,2H),7.68-7.50(m,3H),6.77-6.53(m,2H),4.99(dd,J＝13.3,5.0Hz,1H),4.60(s,2H),4.25(dd,J＝55.3,17.3Hz,2H),3.60(dd,J＝20.2,16.2Hz,5H),3.09(dd,J＝29.4,21.6Hz,4H),2.95-2.85(m,1H),2.59(d,J＝16.9Hz,1H),2.33(tt,J＝13.3,6.8Hz,1H),2.04-1.88(m,1H).LCMS(ESI)C₂₈H₂₉FN₇O₃ ⁺[M+H]⁺： calculated 530.23, found 530.3) was prepared according to the procedure of scheme 2.

EXAMPLE 38 preparation of Compound GT-06439

The title compound GT-06439 (orange solid, 42mg, yield 64％).¹H NMR(400MHz,DMSO-d6)δ10.98(d,J＝32.6Hz,2H),9.38(d,J＝1.4Hz,1H),8.98(d,J＝1.4Hz,1H),8.22(dd,J＝7.9,1.7Hz,2H),7.62-7.55(m,3H),7.47(d,J＝8.3Hz,1H),7.01-6.83(m,2H),5.04(dd,J＝13.3,5.1Hz,1H),4.62(s,2H),4.24(dd,J＝52.7,17.0Hz,2H),3.57(d,J＝11.5Hz,3H),3.13(d,J＝11.2Hz,2H),2.92(ddd,J＝17.4,16.5,9.6Hz,3H),2.59(d,J＝16.6Hz,1H),2.35(dd,J＝12.9,4.4Hz,1H),2.08-1.89(m,1H).LCMS(ESI)C₂₈H₃₀N₇O₃ ⁺[M+H]⁺： calculated 512.24 found 512.3) was prepared according to the procedure of scheme 2.

EXAMPLE 39 preparation of Compound GT-06440

The title compound GT-06440 (grey solid, 31mg, yield 46％).¹H NMR(400MHz,DMSO-d6)δ10.97(s,2H),9.38(d,J＝1.4Hz,1H),8.97(d,J＝1.4Hz,1H),8.22(dd,J＝7.9,1.7Hz,2H),7.62-7.54(m,3H),7.43(d,J＝8.2Hz,1H),7.32(t,J＝7.7Hz,1H),5.05(dd,J＝13.3,5.1Hz,1H),4.61(s,2H),4.46(d,J＝16.8Hz,1H),4.28(d,J＝16.8Hz,1H),3.56(s,2H),3.42(s,3H),3.11(s,4H),2.97-2.85(m,1H),2.59(d,J＝17.2Hz,1H),2.40(qd,J＝13.5,4.5Hz,1H),2.03-1.92(m,1H).LCMS(ESI)C₂₈H₂₉FN₇O₃ ⁺[M+H]⁺： calculated 530.23, found 530.3) was prepared according to the procedure of scheme 2.

EXAMPLE 40 preparation of Compound GT-06441

The title compound GT-06441 (pale yellow solid, 38mg, yield 48％).¹H NMR(400MHz,DMSO-d6)δ11.06(s,1H),7.60(d,J＝8.3Hz,1H),7.57-7.52(m,3H),7.52-7.49(m,1H),7.45(dd,J＝13.4,8.4Hz,3H),7.39(d,J＝6.4Hz,1H),7.15(s,1H),7.02(d,J＝7.7Hz,1H),5.04(dd,J＝12.8,5.4Hz,1H),3.40(s,4H),3.21(s,2H),2.94-2.78(m,2H),2.58(d,J＝18.1Hz,3H),2.47(dd,J＝9.5,4.5Hz,1H),2.04-1.94(m,1H).LCMS(ESI)C₃₀H₂₈ClFN₅O₄ ⁺[M+H]⁺： calculated 572.18, found 572.2) was prepared according to the method of scheme 3.

EXAMPLE 41 preparation of Compound GT-06442

The title compound GT-06442 (pale yellow solid, 41mg, yield 50％).¹H NMR(400MHz,DMSO-d6)δ11.08(s,1H),8.12(s,1H),7.62(d,J＝10.3Hz,1H),7.55(dd,J＝7.2,5.4Hz,3H),7.45(dd,J＝18.9,7.6Hz,4H),7.39-7.35(m,1H),5.06(dd,J＝12.8,5.4Hz,1H),3.35(s,3H),3.27(d,J＝6.9Hz,1H),2.88(ddd,J＝16.8,13.8,5.4Hz,2H),2.74(s,1H),2.65-2.51(m,4H),2.50-2.44(m,1H),2.05-1.95(m,1H).LCMS(ESI)C₃₀H₂₆ClFN₅O₅ ⁺[M+H]⁺： calculated 590.16, found 590.2) was prepared according to the method of scheme 3.

EXAMPLE 42 preparation of Compound GT-06443

The title compound GT-06443 (white solid, 44mg, yield 55％).¹H NMR(400MHz,DMSO-d6)δ10.86(s,1H),7.47(dt,J＝7.4,3.1Hz,3H),7.44-7.33(m,4H),7.31(d,J＝6.5Hz,1H),6.59(s,1H),6.45(d,J＝12.4Hz,1H),4.90(dd,J＝13.3,5.1Hz,1H),4.22(d,J＝17.2Hz,1H),4.07(d,J＝17.2Hz,1H),3.31(s,4H),3.22(s,1H),3.10(s,1H),2.89-2.70(m,2H),2.50(d,J＝16.5Hz,2H),2.40-2.15(m,2H),1.91-1.81(m,1H).LCMS(ESI)C₃₀H₂₈ClFN₅O₄ ⁺[M+H]⁺： calculated 576.18, found 576.2) was prepared according to the procedure of scheme 3.

EXAMPLE 43 preparation of Compound GT-06444

The title compound GT-06444 (white solid, 36mg, yield 47％).¹H NMR(400MHz,DMSO-d6)δ10.93(s,1H),7.57-7.52(m,3H),7.52-7.40(m,5H),7.40-7.36(m,1H),6.89(s,1H),6.81(d,J＝8.3Hz,1H),5.01(dd,J＝13.3,5.1Hz,1H),4.21(dd,J＝54.5,16.9Hz,2H),3.48(s,2H),3.18(s,1H),2.89(ddd,J＝18.7,13.5,5.2Hz,2H),2.68(s,1H),2.58(d,J＝16.9Hz,2H),2.48-2.26(m,2H),1.99-1.90(m,1H).LCMS(ESI)C₃₀H₂₉ClN₅O₄ ⁺[M+H]⁺： calculated 558.19, found 558.2) was prepared according to the procedure of scheme 3.

EXAMPLE 44 preparation of Compound GT-06445

The title compound GT-06445 (white solid, 32mg, yield 40％).¹H NMR(400MHz,DMSO-d6)δ10.88(s,1H),7.50-7.45(m,3H),7.43-7.38(m,2H),7.38-7.33(m,2H),7.32-7.28(m,2H),7.17(t,J＝7.7Hz,1H),4.96(dd,J＝13.3,5.0Hz,1H),4.37(d,J＝16.7Hz,1H),4.19(d,J＝16.7Hz,1H),3.13(s,2H),2.93-2.74(m,2H),2.73-2.56(m,2H),2.51(d,J＝16.4Hz,2H),2.41-2.24(m,2H),1.93-1.82(m,1H).LCMS(ESI)C₃₀H₂₈ClFN₅O₄ ⁺[M+H]⁺： calculated 576.18, found 576.2) was prepared according to the procedure of scheme 3.

EXAMPLE 45 preparation of Compound GT-06446

The title compound GT-06446 (white solid, 23mg, yield 33％).¹H NMR(400MHz,DMSO-d6)δ10.96(s,2H),9.37(d,J＝1.3Hz,1H),8.98(d,J＝1.2Hz,1H),8.22(dd,J＝7.9,1.6Hz,2H),7.68-7.49(m,3H),7.33(dd,J＝29.4,8.9Hz,2H),5.05(dd,J＝13.3,5.1Hz,1H),4.61(s,2H),4.26(dd,J＝50.0,16.9Hz,2H),3.56(s,2H),3.40(s,3H),3.13(s,4H),2.89(d,J＝13.1Hz,1H),2.59(d,J＝16.5Hz,1H),2.37(dd,J＝13.1,4.4Hz,1H),2.03-1.90(m,1H).LCMS(ESI)C₂₈H₂₉FN₇O₃ ⁺[M+H]⁺： calculated 530.23, found 530.3) was prepared according to the procedure of scheme 2.

EXAMPLE 46 preparation of Compound GT-06447

The title compound GT-06447 (white solid, 26mg, yield 33％).¹H NMR(400MHz,DMSO-d6)δ10.95(s,1H),7.587.52(m,3H),7.49(dd,J＝12.6,6.8Hz,2H),7.43(d,J＝8.5Hz,2H),7.37(d,J＝6.7Hz,1H),7.34(s,1H),7.23(d,J＝7.2Hz,1H),5.03(dd,J＝13.2,5.1Hz,1H),4.24(dd,J＝53.3,17.0Hz,2H),3.38(s,2H),3.21(s,2H),3.01-2.81(m,2H),2.64(t,J＝33.9Hz,4H),2.33(dd,J＝13.1,4.5Hz,2H),2.01-1.89(m,1H).LCMS(ESI)C₃₀H₂₈ClFN₅O₄ ⁺[M+H]⁺： calculated 576.18, found 576.3) was prepared according to the procedure of scheme 3.

EXAMPLE 47 preparation of Compound GT-06460

The title compound GT-06460 (white solid, 44mg, yield 58％).¹H NMR(400MHz,DMSO-d6)δ11.06(s,1H),7.96(s,1H),7.59(d,J＝8.3Hz,1H),7.27(d,J＝5.6Hz,2H),7.18(t,J＝8.9Hz,2H),7.12(s,1H),7.00(d,J＝7.5Hz,1H),5.03(dd,J＝12.8,5.4Hz,1H),4.16(s,1H),3.43(dd,J＝28.9,7.6Hz,2H),3.32(t,J＝6.5Hz,2H),2.85(ddd,J＝74.1,39.8,33.0Hz,3H),2.57(d,J＝17.2Hz,2H),2.41(dd,J＝34.8,11.0Hz,3H),2.11(d,J＝17.9Hz,1H),2.02-1.87(m,2H),1.46(d,J＝9.9Hz,2H),0.99(d,J＝13.1Hz,6H).LCMS(ESI)C₃₂H₃₅FN₅O₅ ⁺[M+H]⁺： calculated 588.26, found 588.3) was prepared according to the procedure of scheme 3.

EXAMPLE 48 preparation of Compound GT-06461

The title compound GT-06461 (white solid, 48mg, yield 62％).¹H NMR(400MHz,DMSO-d6)δ11.00(s,1H),8.02(s,1H),7.53(d,J＝10.3Hz,1H),7.36(d,J＝7.0Hz,1H),7.23-7.15(m,2H),7.09(t,J＝8.9Hz,2H),4.98(dd,J＝12.7,5.4Hz,1H),4.11(s,1H),3.64-3.29(m,2H),3.21(d,J＝25.2Hz,1H),2.93-2.58(m,3H),2.50(d,J＝19.5Hz,3H),2.41-2.20(m,3H),2.06(s,1H),1.96-1.78(m,2H),1.39(d,J＝9.8Hz,2H),0.92(d,J＝10.6Hz,6H).LCMS(ESI)C₃₂H₃₄F₂N₅O₅ ⁺[M+H]⁺： calculated 606.25, found 606.3) was prepared according to the procedure of scheme 3.

EXAMPLE 49 preparation of Compound GT-06462

The title compound GT-06462 (white solid, 40mg, yield 54％).¹H NMR(400MHz,DMSO-d6)δ10.93(s,1H),7.41(d,J＝8.4Hz,1H),7.27(dd,J＝8.7,5.6Hz,2H),7.17(t,J＝8.9Hz,3H),6.86(s,1H),6.79(d,J＝8.3Hz,1H),5.01(dd,J＝13.3,5.1Hz,1H),4.20(dd,J＝54.5,16.9Hz,2H),3.32-3.01(m,3H),2.952.67(m,2H),2.58(d,J＝16.8Hz,2H),2.33(ddd,J＝23.6,17.6,12.0Hz,5H),2.17-1.83(m,4H),1.51-1.36(m,2H),0.99(d,J＝13.0Hz,6H).LCMS(ESI)C₃₂H₃₇FN₅O₄ ⁺[M+H]⁺： calculated 574.28, found 574.3) was prepared according to the procedure of FIG. 3.

EXAMPLE 50 preparation of Compound GT-06463

The title compound GT-06463 (white solid, 35mg, yield 46％).¹H NMR(400MHz,DMSO-d6)δ10.95(s,1H),7.36(d,J＝8.2Hz,1H),7.337.23(m,3H),7.18(dd,J＝17.3,8.4Hz,3H),5.03(dd,J＝13.3,5.0Hz,1H),4.43(d,J＝16.7Hz,1H),4.25(d,J＝16.7Hz,1H),3.37(s,3H),3.022.83(m,2H),2.58(d,J＝13.4Hz,3H),2.462.28(m,4H),2.00(t,J＝42.5Hz,4H),1.54-1.40(m,2H),0.99(d,J＝11.2Hz,6H).LCMS(ESI)C₃₂H₃₆F₂N₅O₄ ⁺[M+H]⁺： calculated 592.27, found 592.3) was prepared according to the procedure of scheme 3.

EXAMPLE 51 preparation of Compound GT-06464

The title compound GT-06464 (white solid, 46mg, yield 61％).¹H NMR(400MHz,DMSO-d6)δ10.94(s,1H),7.55(s,1H),7.33-7.23(m,2H),7.17(t,J＝8.9Hz,2H),6.64(s,1H),6.50(d,J＝12.3Hz,1H),4.97(dd,J＝13.3,5.1Hz,1H),4.28(d,J＝17.2Hz,1H),4.14(d,J＝17.2Hz,1H),3.353.25(m,3H),2.98-2.72(m,2H),2.63(dd,J＝45.2,12.5Hz,3H),2.47-2.25(m,4H),1.97(dd,J＝46.3,41.1Hz,4H),1.53-1.39(m,2H),0.99(d,J＝13.3Hz,6H).LCMS(ESI)C₃₂H₃₆F₂N₅O₄ ⁺[M+H]⁺： calculated 592.27, found 592.3) was prepared according to the procedure of scheme 3.

EXAMPLE 52 preparation of Compound GT-06465

The title compound GT-06465 (white solid, 14mg, yield 41％).¹H NMR(400MHz,DMSO-d6)δ10.99(s,1H),7.93(s,1H),7.52(d,J＝8.4Hz,1H),7.34(d,J＝8.5Hz,2H),7.18(d,J＝8.1Hz,2H),7.05(s,1H),6.93(d,J＝8.2Hz,1H),4.96(dd,J＝12.8,5.3Hz,1H),4.11(s,1H),2.86-2.58(m,3H),2.58-2.46(m,3H),2.39-2.23(m,3H),2.11-1.78(m,4H),1.38(s,2H),0.92(d,J＝10.3Hz,6H).LCMS(ESI)C₃₂H₃₅ClN₅O₅ ⁺[M+H]⁺： calculated 604.23, found 604.3) was prepared according to the procedure of scheme 3.

EXAMPLE 53 preparation of Compound GT-06466

The title compound GT-06466 (white solid, 16mg, yield 46％).¹H NMR(400MHz,DMSO-d6)δ11.01(s,1H),8.01(s,1H),7.54(d,J＝10.3Hz,1H),7.41 7.31(m,3H),7.17(d,J＝8.3Hz,2H),4.99(dd,J＝12.8,5.4Hz,1H),4.13(s,1H),3.56-3.30(m,2H),2.92-2.61(m,3H),2.53(dd,J＝32.1,16.3Hz,3H),2.31(dd,J＝55.2,10.1Hz,3H),2.19-1.75(m,4H),1.38(s,2H),0.92(d,J＝3.9Hz,6H).LCMS(ESI)C₃₂H₃₄ClFN₅O₅ ⁺[M+H]⁺： calculated 622.22, found 622.3) was prepared according to the procedure of scheme 3.

EXAMPLE 54 preparation of Compound GT-06467

The title compound GT-06467 (white solid, 8mg, yield 22％).¹H NMR(400MHz,DMSO-d6)δ10.88(s,1H),7.31(dd,J＝15.6,8.4Hz,3H),7.23-7.07(m,4H),4.96(dd,J＝13.3,5.1Hz,1H),4.36(d,J＝16.8Hz,1H),4.18(d,J＝16.8Hz,1H),3.32(s,3H),2.95-2.69(m,2H),2.54(t,J＝22.2Hz,4H),2.41-2.17(m,4H),2.10-1.82(m,3H),1.39(d,J＝10.8Hz,2H),0.92(d,J＝8.0Hz,6H).LCMS(ESI)C₃₂H₃₆ClFN₅O₄+⁺[M+H]⁺： calculated 608.24, found 608.3) was prepared according to the procedure of scheme 3.

EXAMPLE 55 preparation of Compound GT-06468

The title compound GT-06468 (white solid, 15mg, yield 44％).¹H NMR(400MHz,DMSO-d6)δ10.87(s,1H),7.51(s,1H),7.33(d,J＝8.5Hz,2H),7.18(d,J＝8.3Hz,2H),6.58(s,1H),6.44(d,J＝12.3Hz,1H),4.90(dd,J＝13.3,5.1Hz,1H),4.21(d,J＝17.2Hz,1H),4.07(d,J＝17.2Hz,1H),3.29-2.97(m,3H),2.88-2.67(m,2H),2.56(dd,J＝44.4,12.2Hz,3H),2.38-2.18(m,4H),1.91(dd,J＝44.6,39.7Hz,4H),1.39(d,J＝9.8Hz,2H),0.92(d,J＝10.8Hz,6H).LCMS(ESI)C₃₂H₃₆ClFN₅O₄ ⁺[M+H]⁺： calculated 608.24, found 608.3) was prepared according to the method of FIG. 3.

EXAMPLE 56 preparation of Compound GT-06469

The title compound GT-06469 (yellow solid, 10mg, yield 13％).¹H NMR(400MHz,DMSO-d6)δ10.99(s,1H),9.87(s,1H),8.32(s,1H),7.54(d,J＝8.3Hz,1H),7.40(d,J＝8.1Hz,2H),7.15-7.07(m,3H),6.95(d,J＝6.6Hz,1H),4.97(dd,J＝12.7,5.2Hz,1H),3.55(s,2H),3.05-2.74(m,8H),2.62-2.46(m,2H),2.27(s,2H),2.05-1.85(m,4H),1.41(s,2H),0.90(s,6H).LCMS(ESI)C₃₂H₃₇ClN₅O₄ ⁺[M+H]⁺： calculated 590.25, found 590.3) was prepared according to the procedure of scheme 1.

EXAMPLE 57 preparation of Compound GT-06470

The title compound GT-06470 (yellow solid, 18mg, yield 28％).¹H NMR(400MHz,DMSO-d6)δ11.08(s,1H),9.82(s,1H),8.42(s,1H),7.64(d,J＝10.3Hz,1H),7.50(dd,J＝17.3,7.6Hz,3H),7.16(d,J＝8.3Hz,2H),5.06(dd,J＝12.8,5.4Hz,1H),3.63(s,2H),3.17(d,J＝11.5Hz,3H),3.12-2.79(m,6H),2.56(dd,J＝15.6,12.3Hz,2H),2.33(s,2H),2.06-1.98(m,3H),1.49(t,J＝5.9Hz,2H),0.97(s,6H).LCMS(ESI)C₃₂H₃₆ClFN₅O₄ ⁺[M+H]⁺： calculated 608.24, found 608.3) was prepared according to the procedure of scheme 1.

EXAMPLE 58 preparation of Compound GT-06471

The title compound GT-06471 (yellow solid, 13mg, yield 19％).¹H NMR(400MHz,DMSO-d6)δ10.96(s,1H),9.70(s,1H),7.73(s,1H),7.48(d,J＝8.3Hz,2H),7.38(d,J＝8.2Hz,1H),7.27(t,J＝7.8Hz,1H),7.17(d,J＝8.3Hz,2H),5.04(dd,J＝13.3,5.1Hz,1H),4.45(d,J＝16.8Hz,1H),4.27(d,J＝16.8Hz,1H),3.61(s,2H),3.31-3.25(m,1H),3.09(d,J＝12.2Hz,2H),2.89(dd,J＝22.5,8.7Hz,5H),2.70-2.52(m,2H),2.45-2.28(m,3H),2.06-1.90(m,3H),1.49(t,J＝6.0Hz,2H),0.98(s,6H).LCMS(ESI)C₃₂H₃₈ClFN₅O₃ ⁺[M+H]⁺： calculated 594.26, found 594.3) was prepared according to the procedure of scheme 1.

EXAMPLE 59 preparation of Compound GT-06472

The title compound GT-06472 (yellow solid, 13mg, yield 20％).¹H NMR(400MHz,DMSO-d6)δ10.95(s,1H),9.94(s,1H),7.99(s,1H),7.46(t,J＝9.6Hz,2H),7.16(d,J＝8.3Hz,2H),6.71-6.54(m,2H),4.98(dd,J＝13.3,5.1Hz,1H),4.29(d,J＝17.1Hz,1H),4.15(d,J＝17.1Hz,1H),3.61(s,2H),3.28-3.23(m,1H),3.08-2.84(m,7H),2.63-2.53(m,2H),2.32(d,J＝12.6Hz,3H),2.05(s,2H),1.99-1.91(m,1H),1.49(t,J＝6.2Hz,2H),0.97(s,6H).LCMS(ESI)C₃₂H₃₈ClFN₅O₃ ⁺[M+H]⁺： calculated 594.26, found 594.3) was prepared according to the procedure of scheme 1.

EXAMPLE 60 preparation of Compound GT-06473

The title compound GT-06473 (yellow solid, 14mg, yield 21％).¹H NMR(400MHz,DMSO-d6)611.08(d,J＝8.3Hz,1H),9.92(s,1H),8.38(s,1H),7.61(d,J＝8.3Hz,1H),7.27-6.94(m,6H),5.04(dd,J＝12.8,5.4Hz,1H),3.70-3.52(m,2H),3.37(s,1H),3.32(s,2H),3.12-2.83(m,6H),2.56(dd,J＝17.4,12.2Hz,2H),2.34(s,2H),2.09-1.95(m,3H),1.49(t,J＝6.4Hz,2H),0.98(s,6H).LCMS(ESI)C₃₂H₃₇FN₅O₄ ⁺[M+H]⁺： calculated 574.28, found 574.3) was prepared according to the procedure of scheme 1.

EXAMPLE 61 preparation of Compound GT-06474

The title compound GT-06474 (yellow solid, 14mg, yield 20％).¹H NMR(400MHz,DMSO-d6)δ11.08(s,1H),9.69(s,1H),8.41(s,1H),7.64(d,J＝10.3Hz,1H),7.52(d,J＝6.8Hz,1H),7.27-7.12(m,4H),5.06(dd,J＝12.8,5.4Hz,1H),3.64(s,2H),3.31-3.23(m,2H),3.14(d,J＝11.5Hz,2H),3.08-2.82(m,5H),2.68-2.53(m,2H),2.31(s,2H),2.08-1.96(m,3H),1.48(d,J＝6.1Hz,2H),0.98(s,6H).LCMS(ESI)C₃₂H₃₆F₂N₅O₄ ⁺[M+H]⁺： calculated 592.27, found 592.3) was prepared according to the method of scheme 1.

EXAMPLE 62 preparation of Compound GT-06475

The title compound GT-06475 (yellow solid, 12mg, yield 18％).¹H NMR(400MHz,DMSO-d6)δ10.96(s,1H),9.75(s,1H),7.73(s,1H),7.38(d,J＝8.2Hz,1H),7.22(dt,J＝13.9,8.6Hz,5H),5.04(dd,J＝13.3,5.1Hz,1H),4.45(d,J＝16.9Hz,1H),4.27(d,J＝16.8Hz,1H),3.61(d,J＝3.8Hz,2H),3.33-3.32(m,1H),3.10(t,J＝11.5Hz,2H),2.92(dd,J＝19.3,11.8Hz,5H),2.57(dd,J＝17.7,10.6Hz,2H),2.45-2.28(m,3H),2.06(s,2H),2.00-1.91(m,1H),1.49(t,J＝6.1Hz,2H),0.98(s,6H).LCMS(ESI)C₃₂H₃₈F₂N₅O₃ ⁺[M+H]⁺： calculated 578.29, found 578.3) was prepared according to the procedure of scheme 1.

EXAMPLE 63 preparation of Compound GT-06476

The title compound GT-06476 (yellow solid, 10mg, yield 14％).¹H NMR(400MHz,DMSO-d6)δ10.94(s,1H),9.94(s,1H),7.98(s,1H),7.21(dt,J＝14.0,8.5Hz,4H),6.74-6.51(m,2H),4.98(dd,J＝13.3,5.0Hz,1H),4.29(d,J＝17.2Hz,1H),4.15(d,J＝17.2Hz,1H),3.60(s,2H),3.31-3.28(m,1H),3.14-2.81(m,7H),2.62-2.52(m,2H),2.38-2.25(m,3H),2.05(s,2H),1.98-1.89(m,1H),1.49(t,J＝6.1Hz,2H),0.98(s,6H).LCMS(ESI)C₃₂H₃₈F₂N₅O₃ ⁺[M+H]⁺： calculated 578.29, found 578.3) was prepared according to the procedure of scheme 1.

EXAMPLE 64 preparation of Compound GT-06536

The title compound GT-06536 (yellow solid, 14mg, yield 20％).¹H NMR(400MHz,DMSO-d6)δ10.94(d,J＝7.6Hz,1H),9.85(s,1H),7.60(d,J＝19.5Hz,1H),7.44(d,J＝8.4Hz,1H),7.25(t,J＝8.8Hz,2H),7.17(dd,J＝8.4,5.7Hz,2H),6.90(s,1H),6.84(d,J＝8.7Hz,1H),5.02(dd,J＝13.2,5.0Hz,1H),4.21(dd,J＝52.6,16.8Hz,2H),3.60(s,2H),3.30-3.26(m,1H),3.05-2.80(m,7H),2.65-2.52(m,2H),2.33(s,3H),2.05(s,2H),1.99-1.92(m,1H),1.49(t,J＝6.0Hz,2H),0.98(s,6H).LCMS(ESI)C₃₂H₃₉FN₅O₃ ⁺[M+H]⁺： calculated 560.30, found 560.4) was prepared according to the procedure of scheme 1.

EXAMPLE 65 preparation of Compound GT-06537

The title compound GT-06537 (yellow solid, 15mg, yield 19％).¹H NMR(400MHz,DMSO-d6)δ10.88(s,1H),9.73(s,1H),7.65(s,1H),7.39(t,J＝9.4Hz,2H),7.27(d,J＝10.7Hz,1H),7.16(d,J＝7.2Hz,1H),7.08(t,J＝9.1Hz,2H),4.96(dd,J＝13.3,5.0Hz,1H),4.15(dd,J＝50.2,16.9Hz,2H),3.54(s,2H),3.34(s,1H),3.05(s,2H),2.942.75(m,5H),2.50(dd,J＝16.8,10.8Hz,2H),2.29(dd,J＝15.7,11.4Hz,3H),1.97(s,2H),1.93-1.83(m,1H),1.42(t,J＝6.1Hz,2H),0.90(s,6H).LCMS(ESI)C₃₂H₃₈ClFN₅O₃ ⁺[M+H]⁺： calculated 594.26, found 594.3) was prepared according to the procedure of scheme 1.

EXAMPLE 66 preparation of Compound GT-06538

The title compound GT-06538 (yellow solid, 18mg, yield 21％).¹H NMR(400MHz,DMSO-d6)δ10.88(s,1H),9.62(s,1H),7.64(s,1H),7.28(d,J＝10.7Hz,1H),7.17(dd,J＝10.0,7.8Hz,3H),7.10(t,J＝7.0Hz,2H),4.96(dd,J＝13.2,5.1Hz,1H),4.15(dd,J＝49.8,16.9Hz,2H),3.54(s,2H),3.23-3.19(m,1H),3.02(s,2H),2.93-2.77(m,5H),2.56-2.44(m,2H),2.24(d,J＝7.6Hz,2H),1.98(s,2H),1.93-1.84(m,1H),1.42(t,J＝6.2Hz,2H),0.90(s,6H).LCMS(ESI)C₃₂H₃₈F₂N₅O₃ ⁺[M+H]⁺： calculated 578.29, found 578.3) was prepared according to the procedure of scheme 1.

EXAMPLE 67 preparation of Compound GT-06539

The title compound GT-06539 (white solid, 10mg, yield 14％).¹H NMR(400MHz,DMSO-d6)δ10.95(s,1H),7.40(d,J＝8.4Hz,2H),7.32(d,J＝10.7Hz,1H),7.29-7.19(m,4H),5.03(dd,J＝13.3,5.0Hz,1H),4.23(dd,J＝52.6,17.0Hz,2H),3.44(s,2H),3.00(s,2H),2.90(dd,J＝11.1,6.2Hz,1H),2.59(d,J＝15.6Hz,4H),2.47-2.28(m,4H),2.13(s,1H),1.99-1.91(m,2H),1.47(d,J＝9.9Hz,2H),0.99(d,J＝8.2Hz,6H).LCMS(ESI)C₃₂H₃₆ClFN₅O₄ ⁺[M+H]⁺： calculated 608.24, found 608.3) was prepared according to the procedure of scheme 3.

EXAMPLE 68 preparation of Compound GT-06540

The title compound GT-06540 (white solid, 30mg, yield 39％).¹H NMR(400MHz,DMSO-d6)δ10.94(s,1H),7.367.28(m,2H),7.26(dd,J＝8.5,5.7Hz,2H),7.18(dd,J＝16.6,7.8Hz,3H),5.02(dd,J＝13.2,5.1Hz,1H),4.22(dd,J＝52.8,16.9Hz,2H),3.42(s,2H),3.29(d,J＝6.1Hz,2H),2.92-2.84(m,1H),2.58(d,J＝16.8Hz,4H),2.48-2.28(m,4H),2.12(s,1H),1.93(d,J＝15.0Hz,2H),1.46(dd,J＝11.4,5.8Hz,2H),0.99(d,J＝11.1Hz,6H).LCMS(ESI)C₃₂H₃₆F₂N₅O₄ ⁺[M+H]⁺： calculated 592.27, found 592.3) was prepared according to the procedure of scheme 3.

EXAMPLE 69 preparation of Compound GT-06541

The title compound GT-06541 (white solid, 13mg, yield 19％).¹H NMR(400MHz,DMSO-d6)δ11.88(s,1H),11.07(s,1H),8.44(s,1H),7.92(s,3H),7.62(d,J＝8.2Hz,1H),7.27(d,J＝35.7Hz,5H),7.01(s,1H),5.69(s,1H),5.04(dd,J＝12.7,5.3Hz,1H),3.32-3.04(m,7H),2.89(dd,J＝22.2,9.2Hz,2H),2.58(d,J＝17.9Hz,2H),2.06-1.88(m,1H).LCMS(ESI)C₃₀H₂₈F₂N₅O₄ ⁺[M+H]⁺： calculated 560.21, found 560.2) was prepared according to the procedure of scheme 2.

EXAMPLE 70 preparation of Compound GT-06542

The title compound GT-06542 (white solid, 22mg, yield 30％).¹H NMR(400MHz,DMSO-d6)δ12.06(s,1H),11.07(s,1H),8.46(s,1H),7.84(d,J＝39.2Hz,3H),7.65-7.47(m,5H),7.22(s,1H),7.02(s,1H),5.69(s,1H),5.05(dd,J＝12.7,5.4Hz,1H),3.23(s,4H),3.06(s,3H),2.98-2.81(m,2H),2.58(d,J＝18.1Hz,2H),2.06-1.94(m,1H).LCMS(ESI)C₃₀H₂₈Cl₂N₅O₄ ⁺[M+H]⁺： calculated 592.15, found 592.2) was prepared according to the procedure of scheme 2.

EXAMPLE 71 preparation of Compound GT-06543

The title compound GT-06543 (white solid, 4mg, yield 5％).¹H NMR(400MHz,DMSO-d6)δ11.45(s,1H),11.07(s,1H),8.46(s,1H),7.76(d,J＝8.2Hz,4H),7.63(d,J＝8.2Hz,1H),7.23(d,J＝8.5Hz,1H),7.01(d,J＝8.3Hz,5H),5.48(d,J＝8.1Hz,1H),5.05(dd,J＝12.9,5.2Hz,1H),3.75(s,6H),3.19(d,J＝10.3Hz,4H),3.10(s,3H),2.97-2.78(m,2H),2.68-2.54(m,2H),2.03-1.94(m,1H).LCMS(ESI)C₃₂H₃₄N₅O₆ ⁺[M+H]⁺： calculated 584.25, found 584.3) was prepared according to the procedure of scheme 2.

EXAMPLE 72 preparation of Compound GT-06544

The title compound GT-06544 (yellow solid, 27mg, yield 39％).¹H NMR(400MHz,DMSO-d6)δ11.08(s,1H),10.91(s,1H),8.44(s,1H),8.00(s,1H),7.79(d,J＝8.5Hz,3H),7.64(d,J＝8.3Hz,1H),7.58(t,J＝5.9Hz,4H),7.24(s,1H),7.04(s,1H),5.05(dd,J＝12.8,5.3Hz,1H),4.42(s,2H),3.40(s,2H),3.32-3.19(m,2H),3.13(d,J＝10.8Hz,2H),3.03(s,2H),2.89(dd,J＝15.6,10.1Hz,1H),2.60(dd,J＝36.5,18.6Hz,2H),2.08-1.95(m,1H).LCMS(ESI)C₃₀H₂₉ClN₅O₄ ⁺[M+H]⁺： calculated 558.19, found 558.2) was prepared according to the procedure of scheme 1.

EXAMPLE 73 preparation of Compound GT-06545

The title compound GT-06545 (yellow solid, 24mg, yield 35％).¹H NMR(400MHz,DMSO-d6)δ11.09(d,J＝8.4Hz,1H),10.81(s,1H),8.44(s,1H),7.84-7.69(m,6H),7.64(d,J＝8.3Hz,1H),7.55(d,J＝8.6Hz,2H),7.24(s,1H),7.04(s,1H),5.06(dd,J＝12.9,5.3Hz,1H),4.40(s,2H),3.14(d,J＝11.4Hz,2H),3.07-2.92(m,2H),2.89(dd,J＝15.6,10.4Hz,1H),2.65-2.52(m,2H),2.10-1.91(m,1H).LCMS(ESI)C₃₀H₂₉ClN₅O₄ ⁺[M+H]⁺： calculated 558.19, found 558.2) was prepared according to the procedure of scheme 1.

EXAMPLE 74 preparation of Compound GT-06546

The title compound GT-06546 (yellow solid, 26mg, yield 38％).¹H NMR(400MHz,DMSO-d6)δ11.07(s,1H),10.15(s,1H),8.38(s,1H),7.62(t,J＝8.9Hz,1H),7.28(d,J＝7.3Hz,3H),7.23-7.13(m,1H),7.03(s,1H),5.04(dd,J＝12.7,5.3Hz,1H),4.36(s,2H),3.84(t,J＝5.3Hz,2H),3.67(s,2H),3.40(s,2H),3.32-3.19(m,2H),3.18-2.85(m,6H),2.58(d,J＝18.3Hz,2H),2.38(s,1H),2.04-1.96(m,1H).LCMS(ESI)C₂₉H₃₁FN₅O₅ ⁺[M+H]⁺： calculated 548.23, found 548.2) was prepared according to the procedure of scheme 1.

EXAMPLE 75 preparation of Compound GT-06547

The title compound GT-06547 (yellow solid, 26mg, yield 36％).¹H NMR(400MHz,DMSO-d6)δ11.00(s,1H),10.00(s,1H),8.30(s,1H),7.54(d,J＝8.3Hz,1H),7.43(d,J＝8.3Hz,2H),7.17(d,J＝8.2Hz,2H),7.12(s,1H),6.94(d,J＝7.6Hz,1H),4.97(dd,J＝12.8,5.4Hz,1H),4.29(s,2H),3.62(s,2H),2.93(s,6H),2.79(dd,J＝16.7,5.0Hz,2H),2.51(d,J＝18.3Hz,3H),2.17(s,2H),1.94-1.88(m,1H),1.16(s,6H).LCMS(ESI)C₃₁H₃₅ClN₅O₅ ⁺[M+H]⁺： calculated 592.23, found 592.3) was prepared according to the procedure of scheme 1.

EXAMPLE 76 preparation of Compound GT-07057

The title compound GT-07057 (white solid, 29mg, yield 43％).¹H NMR(500MHz,DMSO-d6)δ11.08(s,1H),7.66(d,J＝8.5Hz,1H),7.37(d,J＝8.4Hz,2H),7.33-7.30(m,2H),7.25-7.20(m,2H),5.07(dd,J＝12.8,5.4Hz,1H),4.24-3.90(m,6H),2.92-2.84(m,1H),2.65-2.55(m,4H),2.27(brs,2H),2.14-1.97(m,3H),1.44-1.39(m,2H),0.98(s,6H).LCMS(ESI)C₃₂H₃₅ClN₅O₅ ⁺[M+H]⁺： calculated 604.23, found 604.3) was prepared according to the procedure of FIG. 3.

EXAMPLE 77 preparation of Compound GT-07058

The title compound GT-07058 (white solid, 48mg, yield 68％).¹H NMR(500MHz,DMSO-d6)δ11.07(s,1H),9.80(d,J＝1.8Hz,1H),8.81(d,J＝1.8Hz,1H),7.48-7.40(m,3H),7.25(d,J＝8.5Hz,2H),6.86(d,J＝1.3Hz,1H),6.21(s,1H),5.04(dd,J＝12.8,5.4Hz,1H),2.94-2.79(m,1H),2.59-2.56(m,1H),2.48-2.46(m,1H),2.35(t,J＝6.2Hz,2H),2.10(s,2H),2.03-1.97(m,1H),1.46(t,J＝6.4Hz,2H),1.02(s,6H).LCMS(ESI)C₂₈H₂₈ClN₄O₅ ⁺[M+H]⁺： calculated 535.17, found 535.2) was prepared according to the procedure of scheme 3.

EXAMPLE 78 preparation of Compound GT-07059

The title compound GT-07059 (white solid, 26mg, yield 39％).¹H NMR(500MHz,DMSO-d6)δ10.98(s,1H),7.62(d,J＝8.0Hz,1H),7.54(s,1H),7.41(d,J＝8.0Hz,1H),7.36(d,J＝8.5Hz,2H),7.20(d,J＝8.5Hz,2H),5.09(dd,J＝13.3,5.1Hz,1H),4.41(d,J＝17.4Hz,1H),4.29(d,J＝17.4Hz,1H),3.03-2.86(m,4H),2.64-2.58(m,2H),2.42-2.36(m,2H),2.27(s,2H),2.21-2.15(m,1H),2.08(d,J＝1.7Hz,2H),2.04-1.94(m,1H),1.80(d,J＝12.5Hz,2H),1.57(s,1H),1.41(t,J＝6.3Hz,2H),1.35(d,J＝9.6Hz,2H),0.98(s,6H).LCMS(ESI)C₃₄H₄₀ClN₄O₄S⁺[M+H]⁺： calculated 635.25, found 635.3) was prepared according to the procedure of scheme 3.

Example 79 preparation of Compound GT-07066

The title compound GT-07066 (white solid, 26mg, yield 38％).1H NMR(500MHz,DMSO-d6)δ10.94(s,1H),8.70(s,1H),7.50(d,J＝8.5Hz,1H),7.40-7.34(m,2H),7.30(d,J＝8.6Hz,1H),7.26-7.19(m,1H),7.08-6.99(m,2H),5.04(dd,J＝13.3,5.1Hz,1H),4.31(d,J＝16.9Hz,1H),4.19(d,J＝16.9Hz,1H),3.33-3.20(m,3H),2.96-2.83(m,1H),2.63-2.54(m,4H),2.52-2.50(m,1H),2.44-2.31(m,2H),2.27(brs,2H),2.08-2.05(m,2H),2.01-1.89(m,1H),1.43-1.35(m,2H),0.98(s,6H).LCMS(ESI)C₃₂H₃₇ClN₅O₄ ⁺[M+H]⁺： calculated 590.25, found 590.3) was prepared according to the procedure of scheme 7.

EXAMPLE 80 preparation of Compound GT-06911

The title compound GT-06911 (white solid, 14mg, yield 35％).¹H NMR(400MHz,DMSO-d6)δ11.10(s,1H),8.80(d,J＝4.0Hz,1H),8.03-7.89(m,1H),7.89-7.61(m,3H),7.60-7.32(m,6H),7.32-7.00(m,2H),5.09(dd,J＝12.9,5.4Hz,1H),3.81(s,3H),3.30-3.06(m,6H),2.87(t,1H),2.70-2.53(m,2H),2.08-1.97(m,1H).LCMS(ESI)C₂₉H₂₉N₆O₄ ⁺[M+H]+： calculated 525.22, found 525.3) was prepared according to the procedure of scheme 2.

EXAMPLE 81 preparation of Compound GT-06902

The title compound GT-06902 (white solid, 16mg, yield 40％).¹H NMR(400MHz,DMSO-d6)δ11.09(s,1H),7.90(d,J＝6.1,3.2Hz,1H),7.70(d,J＝8.5Hz,1H),7.56-7.49(m,3H),7.43-7.35(m,5H),7.32-7.24(m,2H),5.08(dd,J＝12.9,5.3Hz,1H),3.68-3.59(m,4H),3.20-3.11(m,4H),2.88(td,J＝14.2,7.5Hz,1H),2.66-2.52(m,2H),2.13-1.88(m,1H).LCMS(ESI)C₃₀H₂₇ClN₅O₄ ⁺[M+H]⁺： calculated 556.17, found 556.2) was prepared according to the procedure of scheme 1.

EXAMPLE 82 preparation of Compound GT-07209

The title compound GT-07209 (white solid, 5mg, yield 6％).¹H NMR(400MHz,DMSO-d6)δ11.08(s,1H),7.93-7.87(m,1H),7.69(d,J＝8.5Hz,1H),7.57-7.46(m,3H),7.42-7.35(m,4H),7.32-7.25(m,2H),5.07(dd,J＝13.0,5.4Hz,1H),3.63(s,4H),3.27-3.20(m,2H),3.16(s,4H),2.94-2.76(m,2H),2.59(d,J＝16.6Hz,1H),2.08-1.98(m,1H)..LCMS(ESI)C₃₀H₂₉ClN₅O₄ ⁺[M+H]+： calculated 558.19, found 558.2) was prepared according to the method of FIG. 1

EXAMPLE 83 preparation of Compound GT-06903

The title compound GT-06903 (white solid, 22mg, yield 56％).¹H NMR(400MHz,DMSO-d6)δ11.10(s,1H),7.74-7.61(m,1H),7.46-7.31(m,3H),7.31-7.21(m,4H),5.09(dd,J＝12.8,5.4Hz,1H),3.70-3.52(m,5H),3.21(d,J＝25.8Hz,2H),3.14-2.64(m,5H),2.64-2.54(m,2H),2.50-2.30(m,3H),2.06-2.00(m,1H),1.80-1.60(m,3H).LCMS(ESI)C₃₀H₃₁FN₅O₄ ⁺[M+H]⁺： calculated 544.24, found 554.3) was prepared according to the procedure of scheme 1.

EXAMPLE 84 preparation of Compound GT-07211

The title compound GT-07211 (white solid, 22mg, yield 27％).¹H NMR(400MHz,DMSO-d6)δ11.08(s,1H),10.70(s,1H),7.69(dd,J＝14.0,8.4Hz,1H),7.45-7.19(m,6H),5.08(dd,J＝12.9,5.5Hz,1H),3.55(s,6H),3.11-2.80(m,5H),2.66-2.52(m,2H),2.42-2.32(m,1H),2.26(s,3H),2.09-1.96(m,1H),1.69(s,4H).LCMS(ESI)C₃₀H₃₃FN₅O₄ ⁺[M+H]⁺： calculated 546.25, found 546.3) was prepared according to the procedure of scheme 1.

EXAMPLE 85 preparation of Compound GT-06904

The title compound GT-06904 (white solid, 20mg, yield 49％).¹H NMR(400MHz,DMSO-d6)δ11.09(s,1H),7.69(d,J＝8.5Hz,1H),7.46(d,J＝8.5Hz,2H),7.39-7.31(m,3H),7.30-7.22(m,2H),5.07(dd,J＝12.9,5.4Hz,1H),4.37(s,2H),3.82(t,J＝5.5Hz,2H),3.62-3.54(m,4H),3.07-2.96(m,4H),2.93-2.83(m,1H),2.66-2.53(m,2H),2.48(s,2H),2.06-1.98(m,1H).LCMS(ESI)C₂₉H₂₉ClN₅O₅ ⁺[M+H]⁺： calculated 562.19, found 562.2) was prepared according to the procedure of scheme 1.

EXAMPLE 86 preparation of Compound GT-07212

The title compound GT-07212 (white solid, 8mg, yield 10％).¹H NMR(400MHz,DMSO-d6)δ11.08(d,J＝3.8Hz,1H),7.78-7.65(m,1H),7.52-7.24(m,6H),5.14-4.94(m,1H),4.32(d,J＝34.9Hz,2H),3.81(t,J＝5.4Hz,2H),3.66-3.54(m,6H),3.15-2.97(m,4H),2.91-2.81(m,1H),2.64-2.53(m,2H),2.48-2.31(m,2H),2.03(t,J＝12.3Hz,1H).LCMS(ESI)C₂₉H₃₁ClN₅O₅ ⁺[M+H]⁺： calculated 564.20, found 564.2) was prepared according to the method of scheme 1

EXAMPLE 87 preparation of Compound GT-06905

The title compound GT-06905 (white solid, 13mg, yield 31％).¹H NMR(400MHz,DMSO-d6)δ11.10(s,1H),7.70(d,J＝8.5Hz,1H),7.47-7.42(m,2H),7.37(d,J＝2.1Hz,1H),7.30-7.25(m,2H),7.25-7.20(m,2H),5.09(dd,J＝12.9,5.4Hz,1H),3.62-3.55(m,4H),3.05-2.94(m,4H),2.93-2.83(m,1H),2.67-2.54(m,2H),2.40(s,2H),2.18(s,2H),2.04(dd,J＝9.0,3.7Hz,1H),1.47(t,J＝6.5Hz,2H),0.99(s,6H).LCMS(ESI)C₃₂H₃₅ClN₅O₄ ⁺[M+H]⁺： calculated 588.24, found 588.3) was prepared according to the procedure of scheme 1.

EXAMPLE 88 preparation of Compound GT-07214

The title compound GT-07214 (white solid, 18mg, yield 25％).¹H NMR(400MHz,DMSO-d6)δ11.08(s,1H),10.83(s,1H),7.69(dd,J＝14.3,8.5Hz,1H),7.41(ddd,J＝24.0,15.3,5.1Hz,3H),7.32-7.18(m,3H),5.08(dd,J＝12.9,5.6Hz,1H),3.57(d,J＝4.8Hz,4H),3.09-2.79(m,5H),2.63-2.53(m,3H),2.37(d,J＝5.1Hz,1H),2.21(d,J＝43.8Hz,2H),2.02(d,J＝11.7Hz,3H),1.44(s,2H),0.97(d,J＝5.0Hz,6H).LCMS(ESI)C₃₂H₃₇ClN₅O₄ ⁺[M+H]⁺： calculated 590.25, found 590.3) was prepared according to the procedure of scheme 1.

EXAMPLE 89 preparation of Compound GT-06907

The title compound GT-06907 (pale yellow solid, 28mg, yield 43％).¹H NMR(500MHz,)δ11.13(s,1H),11.03(s,1H),8.07(d,J＝7.6Hz,1H),7.83(s,1H),7.65(d,J＝8.3Hz,2H),7.51(d,J＝8.4Hz,2H),7.42-7.39(m,1H),7.39-7.37(m,1H),7.35(s,1H),7.34(s,1H),7.26(d,J＝7.4Hz,1H),7.24(s,1H),5.02(dd,J＝12.8,5.4Hz,1H),2.82(d,J＝2.0Hz,1H),2.51(t,J＝15.2Hz,2H),1.96(d,J＝5.0Hz,1H).LCMS(ESI)C₂₆H₂₀ClN₄O₄ ⁺[M+H]⁺： calculated 487.12, found 487.2) was prepared according to the procedure of scheme 1.

EXAMPLE 90 preparation of Compound GT-06908

The title compound GT-06908 (pale yellow solid, 21mg, yield 33％).¹H NMR(500MHz,)δ11.01(s,1H),10.79(s,1H),7.60(d,J＝8.3Hz,1H),7.52(s,1H),7.25-7.20(m,2H),7.18(d,J＝8.9Hz,2H),4.99(dd,J＝12.8,5.4Hz,1H),3.26(s,1H),2.81(d,J＝2.0Hz,1H),2.58-2.45(m,2H),2.40(d,J＝4.6Hz,1H),2.36(s,2H),1.95(d,J＝5.4Hz,1H),1.66(s,4H).LCMS(ESI)C₂₆H₂₄FN₄O₄ ⁺[M+H]⁺： calculated 475.18, found 475.3) was prepared according to the method of scheme 1.

EXAMPLE 91 preparation of Compound GT-06909

The title compound GT-06909 (pale yellow solid, 10mg, yield 15％).¹H NMR(500MHz,)δ11.10(s,1H),10.90(s,1H),7.69(d,J＝8.3Hz,1H),7.61(s,1H),7.50(d,J＝8.4Hz,2H),7.26(d,J＝8.4Hz,2H),7.20(s,1H),5.09(dd,J＝12.8,5.4Hz,1H),2.92-2.89(m,1H),2.60(d,J＝19.8Hz,1H),2.54(s,2H),2.23(s,2H),2.06-2.02(m,1H),1.54(t,J＝6.5Hz,2H),1.25(s,2H),1.02(s,6H).LCMS(ESI)C₂₈H₂₈ClN₄O₄ ⁺[M+H]⁺： calculated 519.18, found 519.2) was prepared according to the method of scheme 1.

EXAMPLE 92 preparation of Compound GT-06906

The title compound GT-06906 (pale yellow solid, 6mg, yield 10%) was prepared according to the procedure of scheme 1. LCMS (ESI) C ₂₅H₂₂N₅O₄ ⁺[M+H]⁺ calculated 456.17, found 456.2.

EXAMPLE 93 preparation of Compound GT-06910

The title compound GT-06910 (pale yellow solid, 10mg, 12% yield) was prepared according to the method of scheme 1. LCMS (ESI) C ₂₈H₂₈ClN₄O₄ ⁺[M+H]⁺ calculated 519.18, found 519.2.

EXAMPLE 94 preparation of Compound GT-06962

The title compound GT-06962 (17 mg, white solid, yield 27％).¹H NMR(400MHz,MeOD)δ7.49(d,J＝8.5Hz,2H),7.45(d,J＝8.2Hz,1H),7.37-7.31(m,1H),7.24(d,J＝8.4Hz,2H),5.08(dd,J＝13.3,5.1Hz,1H),4.45(q,J＝16.7Hz,2H),4.33(s,2H),3.94(t,J＝5.5Hz,2H),3.79(s,2H),3.52(d,J＝8.9Hz,2H),3.20-3.09(m,2H),3.03-2.93(m,4H),2.87(dd,J＝13.4,5.2Hz,1H),2.80-2.71(m,1H),2.55-2.42(m,3H),2.17-2.11(m,1H).LCMS(ESI)C₂₉H₃₂ClFN₅O₄ ⁺[M+H]⁺： calculated 558.21, found 568.3) was prepared according to the procedure of scheme 1.

Example 95 preparation of Compound GT-06963

The title compound GT-06963 (17 mg, white solid, yield 27％).¹H NMR(400MHz,MeOD)δ7.47(d,J＝8.2Hz,2H),7.23(d,J＝8.2Hz,2H),6.72(s,1H),6.60(d,J＝12.7Hz,1H),5.03(dd,J＝13.8,5.5Hz,1H),4.42-4.25(m,4H),4.01-3.87(m,2H),3.85-3.71(m,2H),3.54-3.45(m,2H),3.19-3.07(m,2H),3.05-2.84(m,5H),2.80-2.71(m,1H),2.54-2.45(m,2H),2.44-2.37(m,1H),2.18-2.03(m,1H).LCMS(ESI)C₂₉H₃₂ClFN₅O₄ ⁺[M+H]⁺： calculated 558.21, found 568.3) was prepared according to the procedure of scheme 1.

EXAMPLE 96 preparation of Compound GT-07990

The title compound GT-07990 (27 mg, white solid, yield 48%) was prepared according to the procedure of scheme 1 LCMS (ESI) C ₃₄H₄₂ClN₆O₅ ⁺[M+H]⁺ calculated as 649.29, found 649.2.

EXAMPLE 97 preparation of Compound GT-07996

The title compound GT-07996 (33 mg, white solid, yield 58%) was prepared according to the procedure of scheme 1 LCMS (ESI) C ₃₄H₄₀ClN₆O₆ ⁺[M+H]⁺ calculated as 663.27, found 663.2.

EXAMPLE 98 preparation of Compound GT-08034

The title compound GT-08034 (10 mg, white solid, yield 55％).¹H NMR(400MHz,MeOD)δ7.55-7.47(m,3H),7.36-7.28(m,2H),6.99(s,1H),6.92-6.88(m,1H),5.28-5.00(m,3H),4.40-4.31(m,1H),4.14(s,1H),3.84(s,1H),3.67-3.61(m,2H),3.53-3.48(m,1H),3.30(s,4H),3.17-3.10(m,2H),3.02-2.83(m,2H),2.82-2.68(m,2H),2.55-2.36(m,1H),2.20-2.09(m,1H),2.09-1.98(m,2H).LCMS(ESI)C₂₉H₃₄ClFN₆O₃ ⁺[M+H]⁺： calculated 549.24, found 549.2) was prepared by the method described in scheme 1.

EXAMPLE 99 preparation of Compound GT-08040

The title compound GT-08040 (15 mg, white solid, yield 66％).¹H NMR(400MHz,MeOD)δ7.59(d,J＝8.2Hz,1H),7.52(d,J＝8.3Hz,2H),7.33-7.23(m,3H),7.06(d,J＝8.0Hz,1H),5.04(dd,J＝13.3,6.2Hz,1H),4.13(s,2H),3.84(s,2H),3.67-3.56(m,2H),3.56-3.46(m,2H),3.12(s,4H),2.99(s,2H),2.88-2.64(m,5H),2.14-2.04(m,1H).LCMS(ESI)C₂₉H₃₂ClN₆O₄ ⁺[M+H]⁺： calculated 563.22 found 563.2) was prepared by the method described in relation to scheme 1.

EXAMPLE 100 preparation of Compound GT-08865

The title compound GT-08865 (46 mg, white solid, yield 46％).¹H NMR(400MHz,DMSO-d6)δ11.10(s,1H),7.62(t,J＝7.5Hz,1H),7.50(d,J＝8.3Hz,1H),7.28(s,1H),7.11(d,J＝6.7Hz,1H),5.16-4.98(m,1H),2.84(d,J＝36.1Hz,6H),2.59(d,J＝18.7Hz,5H),2.08-1.98(m,1H),1.04(s,9H).LCMS(ESI)C₂₁H₂₈N₅O₄ ⁺[M+H]⁺： calculated 414.21, found 414.3) was prepared according to the procedure of scheme 5.

EXAMPLE 101 preparation of Compound GT-08531

The title compound GT-08531 (630 mg, white solid, yield 35％).¹H NMR(400MHz,DMSO-d6)δ11.06(s,1H),8.05(s,1H),7.60(d,J＝8.3Hz,1H),7.14(s,1H),7.01(d,J＝7.8Hz,1H),5.04(dd,J＝12.9,5.4Hz,1H),2.92-2.83(m,1H),2.73(dd,J＝45.1,17.9Hz,4H),2.57(dd,J＝19.7,5.9Hz,4H),2.46(d,J＝4.3Hz,2H),2.20(s,3H),2.03-1.96(m,1H).LCMS(ESI)C₁₈H₂₂N₅O₄ ⁺[M+H]⁺： calculated 372.17, found 372.2) was prepared according to the procedure of scheme 5.

EXAMPLE 102 preparation of Compound GT-08644

The title compound GT-08644 (110 mg, white solid, yield 38％).¹H NMR(400MHz,DMSO-d6)δ10.93(s,1H),7.43(d,J＝8.3Hz,1H),7.25(s,1H),6.90(s,1H),6.85-6.78(m,1H),5.02(dd,J＝13.3,5.1Hz,1H),4.30(d,J＝16.8Hz,1H),4.16(d,J＝16.8Hz,1H),2.95-2.85(m,1H),2.72(s,4H),2.59(d,J＝17.5Hz,2H),2.45(s,2H),2.34(ddd,J＝26.4,13.3,4.4Hz,2H),2.20(s,3H),1.99-1.91(m,1H).LCMS(ESI)C₁₈H₂₄N₅O₃ ⁺[M+H]⁺： calculated 358.19, found 358.2) was prepared according to the procedure of scheme 5.

EXAMPLE 103 preparation of Compound GT-08711

The title compound GT-08711 (43 mg, white solid, yield 21％).¹H NMR(400MHz,DMSO-d6)δ11.06(s,1H),8.01(s,1H),7.60(d,J＝8.3Hz,1H),7.16(s,1H),7.03(s,1H),5.04(dd,J＝12.9,5.4Hz,1H),2.93-2.82(m,2H),2.70(d,J＝23.7Hz,4H),2.65-2.52(m,4H),2.15-1.55(m,2H),1.04(s,9H).LCMS(ESI)C₂₁H₂₈N₅O₄ ⁺[M+H]⁺： calculated 414.21, found 414.3) was prepared according to the procedure of scheme 5.

EXAMPLE 104 preparation of Compound GT-09057

The title compound GT-09057 (63 mg, white solid, yield 41％).¹H NMR(400MHz,DMSO-d6)δ11.01(s,1H),9.71(s,1H),7.31(t,J＝7.7Hz,1H),7.14(s,1H),7.09(s,1H),7.07(d,J＝1.2Hz,1H),5.10(dd,J＝13.3,5.0Hz,1H),4.35(d,J＝17.4Hz,1H),4.22(d,J＝17.4Hz,1H),3.46-3.43(m,2H),3.21(d,J＝8.7Hz,2H),3.15(d,J＝12.9Hz,2H),2.99-2.89(m,1H),2.84(s,3H),2.79(s,2H),2.62(d,J＝17.1Hz,1H),2.39(ddd,J＝26.5,13.3,4.4Hz,1H),2.07-1.98(m,1H).LCMS(ESI)C₁₈H₂₄N₅O₃ ⁺[M+H]⁺： calculated 358.19, found 358.2) was prepared according to the method of FIG. 5.

EXAMPLE 105 preparation of Compound GT-09058

The title compound GT-09058 (190 mg, white solid, yield 50％).¹H NMR(400MHz,DMSO-d6)δ11.11(s,1H),9.75(s,1H),7.95(s,1H),7.65(dd,J＝8.4,7.2Hz,1H),7.54(d,J＝8.5Hz,1H),7.15(d,J＝6.7Hz,1H),5.07(dd,J＝12.7,5.4Hz,1H),3.47(s,2H),3.27(s,2H),3.09(s,4H),2.93(d,J＝5.9Hz,1H),2.83(s,3H),2.59(d,J＝19.1Hz,1H),2.54(s,1H),2.10-1.99(m,1H).LCMS(ESI)C₁₈H₂₂N₅O₄ ⁺[M+H]⁺： calculated 372.17, found 372.2) was prepared according to the method of FIG. 5.

EXAMPLE 106 preparation of Compound GT-09917

The title compound GT-09917 (51 mg, white solid, yield 31％).¹H NMR(400MHz,DMSO-d6)δ11.09(s,1H),8.15(s,1H),7.57(d,J＝8.2Hz,1H),7.51-7.39(m,1H),5.05(dd,J＝12.8,5.4Hz,1H),3.35-3.30(m,4H),2.88-2.82(m,1H),2.73(s,4H),2.63-2.51(m,2H),2.02(d,J＝5.7Hz,1H),1.41(d,J＝8.2Hz,9H).LCMS(ESI)C₂₂H₂₇FN₅O₆ ⁺[M+H]⁺： calculated 476.19, found 476.2) was prepared by reference to the method of scheme 5.

EXAMPLE 107 preparation of Compound GT-09918

The title compound GT-09918 (53 mg, white solid, yield 34％).¹H NMR(400MHz,DMSO-d6)δ11.08(s,1H),8.51(s,1H),7.00(s,1H),6.79(s,1H),5.05(dd,J＝12.8,5.4Hz,1H),3.36(s,4H),2.88(ddd,J＝16.8,14.0,5.5Hz,4H),2.58(dd,J＝17.2,2.4Hz,2H),2.46(dd,J＝13.3,4.3Hz,1H),2.05-1.97(m,1H),1.42(s,9H).LCMS(ESI)C₂₂H₂₇FN₅O₆ ⁺[M+H]⁺： calculated 476.19, found 476.2) was prepared by reference to the method of scheme 5.

EXAMPLE 108 preparation of Compound GT-09919

The title compound GT-09919 (32 mg, white solid, yield 19％).¹H NMR(400MHz,DMSO-d6)δ11.03(s,1H),8.03(s,1H),6.79(s,1H),6.47(s,1H),5.00(dd,J＝12.8,5.4Hz,1H),3.47(d,J＝11.2Hz,4H),3.35(s,4H),3.30(s,4H),3.16(s,4H),2.90-2.83(m,1H),2.61-2.52(m,2H),1.97(dd,J＝10.8,5.7Hz,1H),1.42(d,J＝3.1Hz,18H).LCMS(ESI)C₃₁H₄₄N₇O₈ ⁺[M+H]⁺： calculated 642.32, found 642.4) was prepared according to the procedure of scheme 5.

EXAMPLE 109 preparation of Compound GT-08710

The title compound GT-08710 (68 mg, white solid, yield 35％).¹H NMR(400MHz,DMSO-d6)δ11.06(s,1H),8.06(s,1H),7.60(d,J＝8.3Hz,1H),7.15(s,1H),7.02(d,J＝7.1Hz,1H),5.04(dd,J＝12.9,5.3Hz,1H),2.95-2.51(m,12H),1.99(dd,J＝9.5,6.3Hz,1H),1.00(d,J＝5.3Hz,6H).LCMS(ESI)C₂₀H₂₆N₅O₄ ⁺[M+H]⁺： calculated 400.20, found 400.3) was prepared according to the procedure of scheme 5.

EXAMPLE 110 preparation of Compound GT-08881

The title compound GT-08881 (53 mg, white solid, yield 36％).¹H NMR(400MHz,DMSO-d6)δ10.93(s,1H),7.43(d,J＝8.3Hz,1H),7.27(s,1H),6.90(s,1H),6.83(d,J＝8.2Hz,1H),5.02(dd,J＝13.3,5.1Hz,1H),4.29(d,J＝16.8Hz,1H),4.16(d,J＝16.9Hz,1H),2.96-2.82(m,2H),2.74(s,5H),2.58(d,J＝16.4Hz,4H),2.33(dd,J＝13.1,4.4Hz,1H),1.93(dd,J＝12.0,6.9Hz,1H),1.02(s,6H).LCMS(ESI)C₂₀H₂₇N₅O₃ ⁺[M+H]⁺： calculated 385.21, found 385.3) was prepared according to the procedure of scheme 5.

EXAMPLE 111 preparation of Compound GT-08880

The title compound GT-08880 (16 mg, white solid, yield 20％).¹H NMR(400MHz,DMSO-d6)δ11.01(s,1H),7.28(t,J＝7.5Hz,1H),7.04(dd,J＝15.3,7.4Hz,2H),6.76(s,1H),5.09(dd,J＝13.1,4.8Hz,1H),4.28(dd,J＝39.5,17.3Hz,2H),3.00-2.85(m,2H),2.82-2.53(m,8H),2.44-2.25(m,2H),2.08-2.00(m,1H),0.99(s,6H).LCMS(ESI)C₂₀H₂₈N₅O₃ ⁺[M+H]⁺： calculated 386.22, found 386.3) was prepared according to the procedure of scheme 5.

EXAMPLE 112 preparation of Compound GT-08866

The title compound GT-08866 (142 mg, white solid, yield 38％).¹H NMR(400MHz,DMSO-d6)δ11.10(s,1H),7.61(t,J＝7.6Hz,1H),7.49(d,J＝8.4Hz,1H),7.33(s,1H),7.10(d,J＝6.8Hz,1H),5.05(dd,J＝12.3,4.9Hz,1H),2.81(dd,J＝41.7,21.4Hz,5H),2.69-2.51(m,7H),2.07-1.97(m,1H),0.98(d,J＝6.2Hz,6H).LCMS(ESI)C₂₀H₂₆N₅O₄ ⁺[M+H]⁺： calculated 400.20, found 400.3) was prepared according to the procedure of scheme 5.

EXAMPLE 113 preparation of Compound GT-09018

The title compound GT-09018 (8 mg, white solid, yield 18％).¹H NMR(400MHz,DMSO-d6)δ10.92(s,1H),8.20(s,1H),7.42(d,J＝8.4Hz,1H),7.19(s,1H),6.90(s,1H),6.82(d,J＝8.3Hz,1H),5.01(dd,J＝13.3,5.1Hz,1H),4.29(d,J＝16.8Hz,1H),4.15(d,J＝16.8Hz,1H),2.89(s,2H),2.76-2.56(m,8H),2.33(qd,J＝13.7,9.0Hz,1H),2.01-1.90(m,1H),1.03(s,9H).LCMS(ESI)C₂₁H₃₀N₅O₃ ⁺[M+H]⁺： calculated 400.23, found 400.3) was prepared according to the method of scheme 5.

EXAMPLE 114 preparation of Compound GT-09138

The title compound GT-09138 (13 mg, white solid, yield 20％).¹H NMR(400MHz,MeOD)δ7.35(t,J＝7.7Hz,1H),7.25(d,J＝3.4Hz,1H),7.23(dd,J＝4.7,0.9Hz,1H),5.14(dd,J＝13.2,5.2Hz,1H),4.44(s,2H),3.64(d,J＝12.2Hz,2H),3.42-3.32(m,4H),3.02-2.86(m,3H),2.84-2.75(m,1H),2.57-2.45(m,1H),2.26-2.12(m,1H),1.47(s,9H).LCMS(ESI)C₂₁H₃₀N₅O₃ ⁺[M+H]⁺： calculated 400.23, found 400.3) was prepared according to the method of scheme 5.

EXAMPLE 115 preparation of Compound GT-09129

The title compound GT-09129 (24 mg, white solid, yield 39％).¹H NMR(400MHz,MeOD)δ7.73(d,J＝8.2Hz,2H),7.68(d,J＝8.2Hz,2H),7.56(d,J＝8.4Hz,1H),7.04(s,1H),6.96(dd,J＝8.4,1.7Hz,1H),5.08(dd,J＝13.3,5.1Hz,1H),4.46(s,2H),4.43-4.28(m,4H),3.54(d,J＝12.4Hz,2H),3.48-3.41(m,4H),3.29-3.16(m,3H),3.06-2.93(m,4H),2.82-2.72(m,1H),2.51-2.40(m,1H),2.20-2.08(m,1H),1.94(d,J＝14.7Hz,2H),1.88-1.75(m,3H),1.57-1.52(m,1H).LCMS(ESI)C₃₀H₃₉N₆O₃ ⁺[M+H]⁺： calculated 531.31, found 531.3) was prepared according to the method of scheme 2.

EXAMPLE 116 preparation of Compound GT-09130

The title compound GT-09130 (13 mg, white solid, yield 26％).¹H NMR(400MHz,MeOD)δ7.73(d,J＝8.1Hz,2H),7.68(d,J＝8.1Hz,2H),7.48(t,J＝7.3Hz,1H),7.44-7.38(m,1H),5.09(dd,J＝13.3,5.1Hz,1H),4.53-4.45(m,4H),4.36(s,2H),3.55(d,J＝11.3Hz,2H),3.45-4.39(m,4H),3.28-3.22(m,2H),3.13-3.03(m,4H),2.77(d,J＝15.6Hz,1H),2.56-2.41(m,1H),2.37-2.32(m,1H),2.24-2.10(m,1H),1.94(d,J＝14.2Hz,2H),1.89-1.73(m,3H),1.55-1.51(m,1H).LCMS(ESI)C₃₀H₃₈FN₆O₃ ⁺[M+H]⁺： calculated 549.30, found 549.3) was prepared according to the method of scheme 2.

EXAMPLE 117 preparation of Compound GT-09131

The title compound GT-09131 (33 mg, white solid, yield 67％).¹H NMR(400MHz,MeOD)δ7.74(d,J＝8.2Hz,2H),7.69(d,J＝8.2Hz,2H),7.41(d,J＝7.0Hz,1H),7.35(d,J＝10.5Hz,1H),5.09(dd,J＝13.3,5.2Hz,1H),4.47(s,2H),4.43-4.29(m,4H),3.55(d,J＝12.2Hz,2H),3.47-3.40(m,4H),3.25(d,J＝12.1Hz,2H),3.16-3.06(m,2H),3.04-2.95(m,2H),2.82-2.72(m,1H),2.53-2.42(m,1H),2.40-2.33(m,1H),2.24-2.10(m,1H),1.94(d,J＝14.5Hz,2H),1.86-1.75(m,3H),1.56-1.51(m,1H).LCMS(ESI)C₃₀H₃₈FN₆O₃ ⁺[M+H]⁺： calculated 549.30, found 549.3) was prepared according to the method of scheme 2.

EXAMPLE 118 preparation of Compound GT-09132

The title compound GT-09132 (29 mg, white solid, yield 59％).¹H NMR(400MHz,MeOD)δ7.73(d,J＝8.2Hz,2H),7.69(d,J＝8.2Hz,2H),6.78(s,1H),6.67(d,J＝11.9Hz,1H),5.04(dd,J＝13.3,5.1Hz,1H),4.46(s,2H),4.42-4.27(m,4H),3.53(d,J＝12.3Hz,2H),3.48-3.39(m,4H),3.25-3.20(m,2H),3.00(t,J＝12.1Hz,4H),2.80-2.71(m,1H),2.53-2.28(m,2H),2.20-2.07(m,1H),1.94(d,J＝14.5Hz,2H),1.86-1.75(1m,3H),1.59-1.44(m,1H).LCMS(ESI)C₃₀H₃₈FN₆O₃ ⁺[M+H]⁺： calculated 549.30, found 549.3) was prepared according to the method of scheme 2.

EXAMPLE 119 preparation of Compound (GT-09133)

The title compound GT-09133 (32 mg, white solid, yield 65％).¹H NMR(400MHz,MeOD)δ7.74(d,J＝8.2Hz,2H),7.68(d,J＝8.3Hz,2H),7.32(d,J＝7.7Hz,1H),7.23(d,J＝6.5Hz,1H),7.21-7.15(m,1H),5.15(dd,J＝13.2,5.2Hz,1H),4.56-4.45(m,4H),4.35(s,2H),3.57-3.49(m,2H),3.47-3.41(m,4H),3.02-2.96(m,4H),2.82-2.77(m,1H),2.58-2.50(m,1H),2.48-2.34(m,2H),2.31-2.27(m,1H),2.24-2.10(m,1H),1.92(d,J＝15.2Hz,2H),1.85-1.77(m,3H),1.59-1.45(m,1H).LCMS(ESI)C₃₀H₃₉N₆O₃ ⁺[M+H]⁺： calculated 531.31, found 531.3) was prepared according to the method of scheme 2.

EXAMPLE 120 preparation of Compound GT-09134

The title compound GT-09134 (24 mg, white solid, yield 49%) was prepared according to the method of scheme 2 LCMS (ESI) C ₃₂H₄₁N₆O₃ ⁺[M+H]⁺:calculated 557.32, found 557.3.

EXAMPLE 121 preparation of Compound GT-09135

The title compound GT-09135 (30 mg, white solid, yield 61％).¹H NMR(400MHz,MeOD)δ7.79(d,J＝8.2Hz,2H),7.69(d,J＝8.2Hz,2H),7.57(d,J＝8.3Hz,1H),7.02(s,1H),6.95(d,J＝8.3Hz,1H),5.08(dd,J＝13.3,5.1Hz,1H),4.46-4.29(m,6H),4.01(s,2H),3.46(d,J＝12.6Hz,2H),3.19-3.11(m,4H),3.06-2.94(m,2H),2.93-2.83(m,1H),2.80-2.74(m,1H),2.51-2.44(m,4H),2.41-2.33(m,1H),2.19-2.11(m,2H),1.93(d,J＝15.0Hz,2H),1.88-1.73(m,3H),1.60-1.47(m,1H).LCMS(ESI)C₃₂H₄₁N₆O₃ ⁺[M+H]⁺： calculated 557.32, found 557.3) was prepared according to the method of scheme 2.

EXAMPLE 122 preparation of Compound GT-09197

The title compound GT-09197 (16 mg, white solid, yield 33％).¹H NMR(400MHz,MeOD)δ7.66(s,4H),7.57(d,J＝8.2Hz,1H),7.08(s,1H),6.98(d,J＝8.2Hz,1H),5.08(dd,J＝13.3,5.1Hz,1H),4.63(s,2H),4.42-4.30(m,2H),4.45-4.27(m,4H),4.05(t,J＝10.8Hz,2H),3.88(s,1H),3.40(d,J＝11.4Hz,2H),3.03-2.81(m,5H),2.73(d,J＝15.6Hz,1H),2.49-2.30(m,2H),2.18-2.04(m,5H),1.91(d,J＝14.7Hz,2H),1.79(t,J＝12.8Hz,3H),1.57-1.42(m,1H).LCMS(ESI)C₃₃H₄₃N₆O₃ ⁺[M+H]⁺： calculated 571.34, found 571.3) was prepared according to the method of scheme 2.

EXAMPLE 123 preparation of Compound GT-09198

The title compound GT-09198 (26 mg, white solid, yield 53％).¹H NMR(400MHz,MeOD)δ7.75(d,J＝8.1Hz,2H),7.68(d,J＝8.0Hz,2H),7.56(d,J＝8.5Hz,1H),7.06(s,1H),6.95(d,J＝8.0Hz,1H),5.08(dd,J＝13.3,5.1Hz,1H),4.49(s,2H),4.46-4.29(m,4H),3.67-3.54(m,2H),3.54-3.44(m,4H),3.28-3.24(m,1H),3.15-3.08(m,2H),3.03-2.98(m,2H),2.92-2.84(m,1H),2.80-2.74(m,1H),2.46(dd,J＝13.2,4.4Hz,1H),2.42-2.33(m,1H),2.24-2.09(m,3H),1.92(t,J＝13.8Hz,2H),1.89-1.73(m,3H),1.56-1.49(m,1H).LCMS(ESI)C₃₁H₄₁N₆O₃ ⁺[M+H]⁺： calculated 545.32, found 545.3) was prepared according to the method of scheme 2.

EXAMPLE 124 preparation of Compound GT-09199

The title compound GT-09199 (33 mg, white solid, yield 67％).¹H NMR(400MHz,MeOD)δ7.68-7.52(m,5H),7.12-7.03(m,1H),6.99-6.92(m,1H),5.08(dd,J＝13.3,5.0Hz,1H),4.42-4.23(m,7H),3.79-3.57(m,3H),3.22-3.00(m,4H),2.92-2.84(m,2H),2.81-2.66(m,2H),2.54-2.37(m,2H),2.20-2.12(m,2H),1.84(brs,4H),1.67(brs,2H).LCMS(ESI)C₃₁H₃₉N₆O₃ ⁺[M+H]⁺： calculated 543.31, found 543.3) was prepared according to the method of scheme 2.

EXAMPLE 125 preparation of Compound GT-09200

The title compound GT-09200 (33 mg, white solid, yield 67％).¹H NMR(400MHz,MeOD)δ7.79(d,J＝8.1Hz,2H),7.68(d,J＝8.1Hz,2H),7.58-7.51(m,1H),7.07(s,1H),6.99-6.91(m,1H),5.07(dd,J＝13.3,5.0Hz,1H),4.56(d,J＝13.2Hz,1H),4.45-4.31(m,6H),3.83-3.74(m,1H),3.69-3.53(m,1H),3.45(d,J＝12.2Hz,3H),3.03-2.97(m,3H),2.86(dd,J＝12.5,3.9Hz,1H),2.76(d,J＝17.8Hz,1H),2.50-2.34(m,4H),2.26-2.07(m,2H),1.94(d,J＝14.2Hz,2H),1.85-1.78(m,3H),1.58-1.44(m,1H).LCMS(ESI)C₃₁H₃₉N₆O₃ ⁺[M+H]⁺： calculated 543.31, found 543.3) was prepared according to the method of scheme 2.

EXAMPLE 126 preparation of Compound GT-09201

The title compound GT-09201 (34 mg, white solid, yield 69％).¹H NMR(400MHz,MeOD)δ7.82(d,J＝8.0Hz,2H),7.67(d,J＝8.2Hz,2H),7.54(d,J＝8.4Hz,1H),7.20(s,1H),7.08(d,J＝8.4Hz,1H),5.08(dd,J＝13.3,5.1Hz,1H),4.49(s,2H),4.43-4.30(m,4H),3.60(d,J＝11.5Hz,2H),3.52(s,2H),3.45(d,J＝12.1Hz,2H),3.37-3.34(m,2H),3.00(dt,J＝12.5,6.3Hz,2H),2.91-2.82(m,1H),2.81-2.70(m,1H),2.51-2.42(m,1H),2.39-2.24(m,3H),2.19-2.06(m,3H),1.93(d,J＝14.5Hz,2H),1.87-1.77(m,3H),1.57-1.47(m,1H).LCMS(ESI)C₃₂H₄₁N₆O₃ ⁺[M+H]⁺： calculated 557.32, found 557.3) was prepared according to the method of scheme 2.

EXAMPLE 127 preparation of Compound GT-09202

The title compound GT-09202 (37 mg, white solid, yield 75％).¹H NMR(400MHz,MeOD)δ7.74(d,J＝8.2Hz,2H),7.69(d,J＝8.2Hz,2H),7.61(d,J＝8.3Hz,1H),7.32(s,1H),7.12(d,J＝7.3Hz,1H),5.06(dd,J＝12.5,5.5Hz,1H),4.47(s,2H),4.36(s,2H),3.55(d,J＝12.2Hz,2H),3.48-3.41(m,4H),3.25(d,J＝12.6Hz,2H),3.13-2.98(m,4H),2.90-2.80(m,1H),2.77-2.74(m,1H),2.68-2.65(m,1H),2.13-2.09(m,1H),1.94(d,J＝14.6Hz,2H),1.85-1.75(m,3H),1.55-1.49(m,1H).LCMS(ESI)C₃₀H₃₇N₆O₄ ⁺[M+H]⁺： calculated 545.29, found 545.3) was prepared according to the method of scheme 2.

EXAMPLE 128 preparation of Compound GT-09203

The title compound GT-09203 (14 mg, white solid, yield 28％).¹H NMR(400MHz,MeOD)δ7.80-7.72(m,5H),7.47(d,J＝2.2Hz,1H),7.36(dd,J＝8.5,2.3Hz,1H),5.09(dd,J＝12.4,5.4Hz,1H),4.39(s,2H),4.06(d,J＝14.0Hz,2H),3.92-3.85(m,2H),3.74-3.65(m,4H),3.50(d,J＝12.1Hz,2H),3.29-3.25(m,1H),3.02(td,J＝12.3,2.8Hz,2H),2.90-2.81(m,1H),2.80-2.74(m,1H),2.73(s,1H),2.70(s,1H),2.19-2.06(m,1H),1.94(d,J＝14.0Hz,2H),1.89-1.76(m,3H),1.62-1.47(m,1H).LCMS(ESI)C₃₀H₃₇N₆O₄ ⁺[M+H]⁺： calculated 545.29, found 545.3) was prepared according to the method of scheme 2.

EXAMPLE 129 preparation of Compound GT-09213

The title compound GT-09213 (24 mg, white solid, yield 49％).¹H NMR(400MHz,MeOD)δ7.76(q,J＝8.3Hz,4H),7.69(d,J＝8.5Hz,1H),7.20(s,1H),7.18(dd,J＝8.5,2.2Hz,1H),5.11(dd,J＝13.3,5.1Hz,1H),4.51-4.32(m,5H),3.96-3.85(m,5H),3.66-3.58(m,4H),3.50(d,J＝12.3Hz,2H),3.05-2.98(m,2H),2.92-2.84(m,1H),2.82-2.72(m,1H),2.47(dd,J＝13.2,4.7Hz,1H),2.43-2.33(m,1H),2.23-2.10(m,1H),1.94(d,J＝14.0Hz,2H),1.89-1.80(m,3H),1.61-1.49(m,1H).LCMS(ESI)C₃₀H₃₉N₆O₃ ⁺[M+H]⁺： calculated 531.31, found 531.3) was prepared according to the method of scheme 2.

EXAMPLE 130 preparation of Compound GT-09708

The title compound GT-09708 (36 mg, white solid, yield 48％).¹H NMR(400MHz,DMSO-d6)δ10.96(s,1H),7.43(t,J＝8.8Hz,4H),7.32(d,J＝8.8Hz,2H),7.19(d,J＝8.4Hz,2H),6.97(d,J＝8.9Hz,2H),5.04(dd,J＝13.2,5.1Hz,1H),4.45(d,J＝16.7Hz,1H),4.27(d,J＝16.7Hz,1H),3.77(d,J＝13.8Hz,2H),3.70-3.52(m,4H),3.37-3.28(m,4H),3.20(t,J＝12.0Hz,2H),2.90-2.73(m,6H),2.59(d,J＝16.3Hz,1H),2.39(d,J＝12.7Hz,1H),2.34-2.22(m,3H),2.11(s,2H),1.99-1.94(m,1H),1.48(t,J＝6.4Hz,2H),1.02(s,6H).LCMS(ESI)C₄₃H₅₀ClFN₇O₄ ⁺[M+H]⁺： calculated 782.36, found 782.4) was prepared according to the procedure of scheme 3.

EXAMPLE 131 preparation of Compound GT-09709

The title compound GT-09709 (20 mg, white solid, yield 28％).¹H NMR(400MHz,DMSO-d6)δ10.96(s,1H),9.38(s,1H),7.76(s,1H),7.41(d,J＝8.2Hz,1H),7.29(t,J＝7.7Hz,2H),6.94(d,J＝8.0Hz,1H),6.83(d,J＝8.0Hz,1H),5.04(dd,J＝13.3,5.0Hz,1H),4.45(d,J＝16.8Hz,1H),4.27(d,J＝16.8Hz,1H),4.21(s,2H),3.81(s,3H),3.30-3.27(m,2H),3.24-3.15(m,2H),3.07(s,4H),2.96-2.84(m,1H),2.59(d,J＝17.3Hz,1H),2.44-2.35(m,1H),1.98-1.94(m,1H).LCMS(ESI)C₂₅H₂₉FN₅O₅ ⁺[M+H]⁺： calculated 498.21, found 498.2) was prepared according to the procedure of scheme 1.

EXAMPLE 132 preparation of Compound GT-09741

The title compound GT-09741 (19 mg, white solid, yield 33％).¹H NMR(400MHz,DMSO-d6)δ10.95(s,1H),7.36(d,J＝7.7Hz,1H),7.27(t,J＝7.7Hz,1H),7.17(d,J＝8.1Hz,2H),7.11(d,J＝8.1Hz,2H),5.03(dd,J＝13.3,5.1Hz,1H),4.43(d,J＝16.8Hz,1H),4.25(d,J＝16.8Hz,1H),4.10(q,J＝6.4Hz,1H),3.67-3.58(m,1H),2.95-2.83(m,1H),2.75-2.54(m,5H),2.42-2.40(m,4H),2.37-2.29(m,1H),2.02-1.90(m,1H),1.85-1.78(m,1H),1.34(d,J＝7.1Hz,1H),1.28(d,J＝6.8Hz,3H),0.86(dd,J＝6.6,1.3Hz,6H).LCMS(ESI)C₃₀H₃₇FN₅O₄ ⁺[M+H]⁺： calculated 550.28, found 550.3) was prepared according to the procedure of scheme 3.

EXAMPLE 133 preparation of Compound GT-09971

The title compound GT-09971 (9 mg, white solid, yield 23％).¹H NMR(400MHz,MeOD)δ7.69-7.66(m,4H),7.57-7.51(m,5H),7.07-7.03(m,2H),5.82(s,1H),5.17-5.06(m,1H),4.46-4.35(m,2H),3.80-3.60(m,2H),3.27-3.18(m,3H),3.12-3.02(m,3H),2.99-2.96(m,1H),2.92-2.89(m,1H),2.82-2.76(m,1H),2.70-2.60(m,1H),2.52-2.39(m,1H),2.23-2.11(m,1H).LCMS(ESI)C₃₂H₃₂Cl₂N₅O₃ ⁺[M+H]⁺： calculated 604.19, found 604.2) was prepared according to the procedure of scheme 2.

EXAMPLE 134 preparation of Compound GT-09972

The title compound GT-09972 (25 mg, white solid, yield 49％).¹H NMR(400MHz,DMSO-d6)δ10.94(s,1H),7.56-7.52(m,3H),7.50-7.40(m,6H),6.82(s,1H),6.74(d,J＝8.1Hz,1H),5.03(dd,J＝13.3,5.1Hz,1H),4.31(dd,J＝16.7,6.2Hz,1H),4.18(d,J＝17.0Hz,1H),2.96-2.86(m,2H),2.78-2.65(m,5H),2.62-2.55(m,4H),2.43-2.32(m,2H),2.02-1.92(m,1H).LCMS(ESI)C₃₂H₃₁ClN₅O₄ ⁺[M+H]⁺： calculated 584.21, found 584.2) was prepared according to the procedure of scheme 3.

EXAMPLE 135 preparation of Compound GT-09973

The title compound GT-09973 (35 mg, white solid, yield 68％).¹H NMR(400MHz,DMSO-d6)δ10.92(s,1H),7.57-7.51(m,3H),7.50-7.40(m,6H),6.84(s,1H),6.77(d,J＝8.0Hz,1H),5.00(dd,J＝13.2,5.0Hz,1H),4.53(s,1H),4.27(dd,J＝16.9,3.2Hz,1H),4.14(dd,J＝17.0,3.3Hz,1H),3.54-3.42(m,2H),2.97-2.81(m,2H),2.71-2.65(m,2H),2.63-2.54(m,3H),2.35-2.24(m,1H),1.99-1.79(m,2H),1.69(brs,1H).LCMS(ESI)C₃₂H₃₁ClN₅O₄ ⁺[M+H]⁺： calculated 584.21, found 584.2) was prepared according to the procedure of scheme 3.

EXAMPLE 136 preparation of Compound GT-09974

The title compound GT-09974 (29 mg, white solid, yield 57％).¹H NMR(400MHz,DMSO-d6)δ10.92(s,1H),7.56-7.52(m,3H),7.49-7.39(m,7H),6.87(s,1H),6.79(d,J＝8.1Hz,1H),5.01(dd,J＝13.3,5.1Hz,1H),4.28(d,J＝16.9Hz,1H),4.14(d,J＝16.9Hz,1H),3.54-3.43(m,4H),3.21(s,2H),2.96-2.83(m,1H),2.59-2.54(m,2H),2.38-2.25(m,2H),1.97-1.91(m,1H),1.55(brs,2H),1.44(brs,2H).LCMS(ESI)C₃₃H₃₃ClN₅O₄ ⁺[M+H]⁺： calculated 598.22, found 598.3) was prepared according to the procedure of scheme 3.

EXAMPLE 137 preparation of Compound GT-09975

The title compound GT-09975 (26 mg, white solid, yield 50％).¹H NMR(400MHz,DMSO-d6)δ10.93(s,1H),7.56-7.51(m,3H),7.51-7.38(m,6H),6.90(s,1H),6.83(s,1H),5.02(dd,J＝13.3,5.1Hz,1H),4.30(d,J＝16.8Hz,1H),4.19(d,J＝16.8Hz,1H),3.61-3.57(m,4H),3.26-3.11(m,1H),3.05-2.75(m,4H),2.58(d,J＝16.9Hz,2H),2.40-2.26(m,1H),1.97-1.93(m,1H),1.69(brs,1H).LCMS(ESI)C₃₁H₃₁ClN₅O₄ ⁺[M+H]⁺： calculated 572.21, found 572.2) was prepared according to the procedure of scheme 3.

EXAMPLE 138 preparation of Compound GT-09976

The title compound GT-09976 (32 mg, white solid, yield 62％).¹H NMR(400MHz,DMSO-d6)δ10.92(s,1H),7.57-7.53(m,5H),7.49-7.42(m,4H),6.86(s,1H),6.79(d,J＝8.3Hz,1H),5.01(dd,J＝13.3,5.0Hz,1H),4.28(d,J＝16.9Hz,1H),4.15(d,J＝17.0Hz,1H),3.60(s,1H),3.23(s,2H),3.12-2.99(m,1H),2.94-2.83(m,1H),2.70-2.63(m,1H),2.60-2.55(m,2H),2.37-2.28(m,1H),2.04-1.87(m,2H),1.64(s,1H).LCMS(ESI)C₃₁H₂₉ClN₅O₄ ⁺[M+H]⁺： calculated 570.19, found 570.2) was prepared according to the procedure of scheme 3.

EXAMPLE 139 preparation of Compound GT-09977

The title compound GT-09977 (29 mg, white solid, yield 56％).¹H NMR(400MHz,DMSO-d6)δ10.92(s,1H),7.58-7.51(m,4H),7.50-7.36(m,5H),6.91(s,1H),6.81(d,J＝8.4Hz,1H),5.08-4.96(m,1H),4.33-4.24(m,1H),4.15(d,J＝16.3Hz,1H),3.68-3.63(m,4H),3.21-3.08(m,1H),2.97-2.81(m,2H),2.58(d,J＝18.1Hz,2H),2.37-2.29(m,1H),2.02-1.87(m,1H),1.82-1.64(m,1H).LCMS(ESI)C₃₁H₂₉ClN₅O₄ ⁺[M+H]⁺： calculated 570.19, found 570.2) was prepared according to the method of scheme 3.

EXAMPLE 140 preparation of Compound GT-09978

The title compound GT-09978 (27 mg, white solid, yield 52％).¹H NMR(400MHz,DMSO-d6)δ10.92(s,1H),7.60-7.44(m,7H),7.39(d,J＝8.4Hz,2H),6.95(s,1H),6.88(t,J＝8.7Hz,1H),5.01(dd,J＝13.3,5.1Hz,1H),4.28(d,J＝16.8Hz,1H),4.13(dd,J＝17.0,3.4Hz,1H),3.56-3.51(m,4H),3.30-3.18(m,2H),2.98-2.84(m,2H),2.58(d,J＝16.8Hz,2H),2.36-2.30(m,1H),2.07-1.88(m,2H),1.66-1.53(m,1H).LCMS(ESI)C₃₂H₃₁ClN₅O₄ ⁺[M+H]⁺： calculated 584.21, found 584.3) was prepared according to the procedure of scheme 3.

EXAMPLE 141 preparation of Compound GT-09980

The title compound GT-09980 (14 mg, white solid, yield 26％).¹H NMR(400MHz,DMSO-d6)δ10.94(s,1H),7.43(s,1H),7.40(d,J＝8.0Hz,2H),7.29(d,J＝8.4Hz,2H),6.78(s,1H),6.74-6.67(m,1H),5.03(dd,J＝13.4,4.3Hz,1H),4.30(d,J＝16.7Hz,1H),4.17(d,J＝16.8Hz,1H),3.32-3.20(m,5H),2.95-2.84(m,2H),2.72-2.63(m,2H),2.63-2.55(m,4H),2.39-2.27(m,4H),1.98-1.91(m,1H),1.45(t,J＝6.3Hz,2H),0.99(s,6H).LCMS(ESI)C₃₄H₃₉ClN₅O₄ ⁺[M+H]⁺： calculated 616.27, found 616.3) was prepared according to the procedure of scheme 3.

EXAMPLE 142 preparation of Compound GT-09981

The title compound GT-09981 (24 mg, white solid, yield 44％).¹H NMR(400MHz,DMSO-d6)δ10.92(s,1H),7.42-7.38(m,3H),7.28(d,J＝8.5Hz,2H),6.82(s,1H),6.75(d,J＝7.6Hz,1H),5.00(dd,J＝13.2,5.0Hz,1H),4.37(d,J＝4.3Hz,1H),4.27(dd,J＝16.9,3.5Hz,1H),4.13(dd,J＝16.9,2.5Hz,1H),3.75(s,1H),3.32-3.21(m,2H),2.95-2.73(m,3H),2.57(d,J＝17.3Hz,2H),2.41-2.27(m,3H),2.24-2.18(m,1H),2.00-1.88(m,2H),1.78(brs,1H),1.65(brs,1H),1.51-1.43(m,2H),1.27-1.16(m,1H),0.99(d,J＝4.2Hz,6H).LCMS(ESI)C₃₄H₃₉ClN₅O₄ ⁺[M+H]⁺： calculated 616.27, found 616.3) was prepared according to the procedure of scheme 3.

EXAMPLE 143 preparation of Compound GT-09982

The title compound GT-09982 (18 mg, white solid, yield 34％).¹H NMR(400MHz,DMSO-d6)δ10.93(s,1H),7.43-7.36(m,3H),7.28(d,J＝8.4Hz,2H),6.85(s,1H),6.77(d,J＝8.3Hz,1H),5.01(dd,J＝13.4,5.1Hz,1H),4.28(d,J＝16.8Hz,1H),4.14(d,J＝16.9Hz,1H),3.25-3.15(m,3H),2.94-2.85(m,1H),2.58(d,J＝17.7Hz,2H),2.35-2.24(m,5H),2.14(s,3H),2.01-1.86(m,1H),1.43-1.40(m,5H),1.35-1.19(m,2H),0.98(s,6H).LCMS(ESI)C₃₅H₄₁ClN₅O₄ ⁺[M+H]⁺： calculated 630.28, found 630.3) was prepared according to the procedure of scheme 3.

EXAMPLE 144 preparation of Compound GT-09983

The title compound GT-09983 (19 mg, white solid, yield 35％).¹H NMR(400MHz,DMSO-d6)δ10.92(s,1H),7.44-7.36(m,3H),7.32-7.25(m,2H),6.84(d,J＝6.5Hz,1H),6.76(t,J＝8.1Hz,1H),5.01(dd,J＝13.2,5.0Hz,1H),4.28(d,J＝16.8Hz,1H),4.14(d,J＝16.8Hz,1H),3.34-3.18(m,3H),3.03-2.83(m,2H),2.80-2.65(m,2H),2.58(d,J＝15.9Hz,2H),2.39-2.32(m,4H),2.23-2.08(m,1H),1.95-1.91(m,2H),1.74(brs,1H),1.65-1.51(m,1H),1.51-1.37(m,2H),0.99(s,6H).LCMS(ESI)C₃₃H₃₉ClN₅O₄ ⁺[M+H]⁺： calculated 604.27, found 604.3) was prepared according to the procedure of scheme 3.

EXAMPLE 145 preparation of Compound GT-09984

The title compound GT-09984 (37 mg, white solid, yield 68％).¹H NMR(400MHz,DMSO-d6)δ10.92(s,1H),7.43-7.40(m,3H),7.29(d,J＝8.5Hz,2H),6.83(s,1H),6.77(d,J＝8.4Hz,1H),5.01(dd,J＝13.2,5.1Hz,1H),4.27(d,J＝17.0Hz,1H),4.13(d,J＝16.8Hz,1H),3.99(s,1H),3.67(s,1H),3.34-2.99(m,3H),2.89-2.84(m,1H),2.57(d,J＝19.2Hz,2H),2.41-2.18(m,4H),2.00-1.85(m,3H),1.48-1.41(m,2H),1.29(brs,1H),0.96(d,J＝3.3Hz,6H).LCMS(ESI)C₃₃H₃₇ClN₅O₄ ⁺[M+H]⁺： calculated 602.25, found 602.3) was prepared according to the procedure of scheme 3.

EXAMPLE 146 preparation of Compound GT-09985

The title compound GT-09985 (36 mg, white solid, yield 66％).¹H NMR(400MHz,DMSO-d6)δ10.92(s,1H),7.50-7.32(m,4H),7.28(d,J＝8.4Hz,1H),6.88(s,1H),6.79(d,J＝8.0Hz,1H),5.01(dd,J＝13.0,4.7Hz,1H),4.27(d,J＝17.1Hz,1H),4.14(d,J＝16.7Hz,1H),3.40-3.22(m,4H),2.99-2.81(m,2H),2.65-2.52(m,2H),2.43-2.29(m,3H),2.28-2.13(m,2H),2.01-1.85(m,2H),1.76-1.65(m,1H),1.50-1.39(m,2H),0.99(s,6H).LCMS(ESI)C₃₃H₃₇ClN₅O₄ ⁺[M+H]⁺： calculated 602.25, found 602.3) was prepared according to the method of scheme 3.

EXAMPLE 147 preparation of Compound GT-09986

The title compound GT-09986 (25 mg, white solid, yield 46％).¹H NMR(400MHz,DMSO-d6)δ10.92(s,1H),7.46-7.34(m,4H),7.21(d,J＝8.0Hz,1H),7.02-6.82(m,2H),5.01(dd,J＝13.3,5.1Hz,1H),4.28(d,J＝16.7Hz,1H),4.13(d,J＝16.8Hz,1H),3.36-3.24(m,2H),3.24-3.08(m,2H),3.00(s,1H),2.95-2.81(m,1H),2.58(d,J＝16.4Hz,2H),2.38-2.28(m,4H),2.20-2.06(m,1H),2.03-1.88(m,3H),1.72(brs,1H),1.52-1.34(m,3H),0.98(d,J＝14.1Hz,6H).LCMS(ESI)C₃₄H₃₉ClN₅O₄ ⁺[M+H]⁺： calculated 616.27, found 616.3) was prepared according to the procedure of scheme 3.

EXAMPLE 148 preparation of Compound GT-09987

The title compound GT-09987 (25 mg, white solid, yield 47％).¹H NMR(400MHz,DMSO-d6)δ10.94(s,1H),7.42(d,J＝8.4Hz,1H),7.36-7.25(m,2H),7.17(t,J＝7.9Hz,2H),6.87-6.61(m,2H),5.03(dd,J＝13.2,5.0Hz,1H),4.30(d,J＝17.0Hz,1H),4.16(d,J＝16.9Hz,1H),3.38-3.31(m,5H),2.98-2.84(m,2H),2.60-2.51(m,4H),2.44-2.20(m,5H),2.05-1.88(m,2H),1.45(t,J＝6.0Hz,2H),0.99(s,6H).LCMS(ESI)C₃₄H₃₉FN₅O₄ ⁺[M+H]⁺： calculated 600.30, found 600.4) was prepared according to the procedure of scheme 3.

Example 149 preparation of Compound GT-09988

The title compound GT-09988 (32 mg, white solid, yield 61％).¹H NMR(400MHz,DMSO-d6)δ10.92(s,1H),7.41(d,J＝8.3Hz,1H),7.30(dd,J＝8.5,5.7Hz,2H),7.16(t,J＝8.8Hz,2H),6.82(s,1H),6.75(d,J＝8.2Hz,1H),5.01(dd,J＝13.3,5.1Hz,1H),4.36(s,1H),4.27(dd,J＝16.9,3.6Hz,1H),4.13(dd,J＝17.0,2.6Hz,1H),3.76(s,1H),2.89-2.83(m,1H),2.80(d,J＝9.8Hz,2H),2.59-2.52(m,3H),2.46-2.39(m,2H),2.39-2.27(m,2H),2.26-2.13(m,1H),2.01-1.86(m,2H),1.77(brs,1H),1.64(brs,1H),1.54-1.39(m,2H),1.20-1.16(m,1H),0.99(d,J＝3.8Hz,6H).LCMS(ESI)C₃₄H₃₉FN₅O₄ ⁺[M+H]⁺： calculated 600.30, found 600.4) was prepared according to the procedure of scheme 3.

Example 150 preparation of Compound GT-09989

The title compound GT-09989 (28 mg, white solid, yield 54％).¹H NMR(400MHz,DMSO-d6)δ10.93(s,1H),7.42(d,J＝8.3Hz,1H),7.30(dd,J＝8.7,5.6Hz,2H),7.18(t,J＝8.9Hz,2H),6.88(s,1H),6.80(d,J＝8.4Hz,1H),5.01(dd,J＝13.2,5.1Hz,1H),4.28(d,J＝17.0Hz,1H),4.15(d,J＝16.9Hz,1H),3.45-3.37(m,4H),3.32(s,2H),3.22(s,2H),2.94-2.85(m,1H),2.58(d,J＝16.5Hz,2H),2.33(dd,J＝12.9,4.5Hz,1H),2.26(brs,2H),2.13(s,2H),1.99-1.87(m,1H),1.50-1.39(m,4H),1.33(brs,1H),0.98(s,6H).LCMS(ESI)C₃₅H₄₁FN₅O₄ ⁺[M+H]⁺： calculated 614.31, found 614.4) was prepared according to the procedure of scheme 3.

EXAMPLE 151 preparation of Compound GT-09990

The title compound GT-09990 (26 mg, white solid, yield 49％).¹H NMR(400MHz,DMSO-d6)δ10.93(s,1H),7.41(d,J＝8.4Hz,1H),7.33-7.28(m,2H),7.19-7.13(m,2H),6.84(d,J＝8.6Hz,1H),6.78(d,J＝9.3Hz,1H),5.01(dd,J＝13.3,4.9Hz,1H),4.28(d,J＝16.8Hz,1H),4.14(d,J＝16.8Hz,1H),3.34-3.26(m,2H),3.00-2.89(m,1H),2.83-2.66(m,2H),2.62-2.55(m,4H),2.44-2.28(m,4H),2.19-2.12(m,1H),2.02-1.85(m,2H),1.75(brs,1H),1.63-1.36(m,3H),0.98(s,6H).LCMS(ESI)C₃₃H₃₉FN₅O₄ ⁺[M+H]⁺： calculated 588.30, found 588.3) was prepared according to the method of scheme 3.

EXAMPLE 152 preparation of Compound GT-09991

The title compound GT-09991 (29 mg, white solid, yield 55％).¹H NMR(400MHz,DMSO-d6)δ10.92(s,1H),7.41(d,J＝8.4Hz,1H),7.30(dd,J＝8.7,5.6Hz,2H),7.19(t,J＝8.9Hz,2H),6.83(s,1H),6.77(d,J＝8.3Hz,1H),5.01(dd,J＝13.3,5.1Hz,1H),4.27(d,J＝16.9Hz,1H),4.13(d,J＝16.9Hz,1H),3.98(s,1H),3.67(s,1H),3.24(brs,2H),3.18-2.98(m,2H),2.96-2.83(m,1H),2.57(d,J＝17.8Hz,2H),2.41-2.29(m,2H),2.29-2.16(m,1H),1.98-1.83(m,3H),1.47-1.41(m,2H),1.30(s,1H),0.96(d,J＝3.2Hz,6H).LCMS(ESI)C₃₃H₃₇FN₅O₄ ⁺[M+H]⁺： calculated 586.28, found 586.3) was prepared according to the procedure of scheme 3.

EXAMPLE 153 preparation of Compound GT-09994

The title compound GT-09994 (33 mg, white solid, yield 62％).¹H NMR(400MHz,DMSO-d6)δ10.93(s,1H),7.45-7.34(m,2H),7.32-7.28(m,1H),7.24(t,J＝8.7Hz,1H),7.17(t,J＝8.8Hz,1H),6.88(s,1H),6.79(d,J＝7.9Hz,1H),5.09-4.96(m,1H),4.27(d,J＝15.1Hz,1H),4.14(d,J＝16.7Hz,1H),3.32-3.23(m,5H),3.01-2.80(m,2H),2.74-2.62(m,2H),2.41-2.32(m,3H),2.28-2.13(m,2H),2.02-1.83(m,2H),1.53-1.38(m,2H),1.00(d,J＝1.6Hz,6H)LCMS(ESI)C₃₃H₃₇FN₅O₄ ⁺[M+H]⁺： calculated 586.28, found 586.3) was prepared according to the procedure of scheme 3.

EXAMPLE 154 preparation of Compound GT-09992

The title compound GT-09992 (73 mg, white solid, yield 77％).¹H NMR(400MHz,DMSO-d6)δ10.95(s,1H),9.42(d,J＝13.9Hz,1H),8.97(d,J＝13.9Hz,1H),8.24-8.21(m,3H),7.63-7.51(m,4H),7.44(d,J＝8.5Hz,1H),6.95(s,2H),5.01(dd,J＝13.3,5.1Hz,1H),4.76(d,J＝3.5Hz,1H),4.66(d,J＝19.9Hz,1H),4.26(d,J＝16.9Hz,1H),4.13(d,J＝16.6Hz,1H),3.59-3.44(m,2H),3.15-2.83(m,7H),2.68-2.56(m,3H),2.26(dd,J＝13.1,4.3Hz,1H),1.99-1.87(m,1H).LCMS(ESI)C₃₀H₃₂N₇O₃ ⁺[M+H]⁺： calculated 538.26, found 538.3) was prepared according to the procedure of scheme 2.

EXAMPLE 155 preparation of Compound GT-09993

The title compound GT-09993 (33 mg, white solid, yield 68％).¹H NMR(400MHz,DMSO-d6)δ10.95(s,1H),9.37(s,1H),9.00(s,1H),8.21(dd,J＝7.9,1.5Hz,2H),7.61-7.56(m,3H),7.48(d,J＝8.3Hz,1H),6.99(s,1H),6.91(d,J＝8.1Hz,1H),5.03(dd,J＝13.3,5.0Hz,1H),4.50(s,2H),4.33(d,J＝16.9Hz,1H),4.21(d,J＝16.9Hz,1H)),4.17(s,2H),3.23-3.10(m,2H),3.01(d,J＝11.7Hz,2H),2.96-2.84(m,1H),2.60(d,J＝17.4Hz,2H),2.45-2.25(m,5H),2.01-1.95(m,1H).LCMS(ESI)C₃₀H₃₂N₇O₃ ⁺[M+H]⁺： calculated 538.26, found 538.3) was prepared according to the procedure of scheme 2.

EXAMPLE 156 preparation of Compound GT-10026

The title compound GT-10026 (15 mg, white solid, yield 32％).¹H NMR(400MHz,DMSO-d6)δ10.94(s,1H),9.30(d,J＝1.2Hz,1H),8.87(d,J＝1.2Hz,1H),8.19(dd,J＝7.7,1.5Hz,2H),7.59-7.54(m,3H),7.47(d,J＝8.3Hz,1H),7.02(s,1H),6.93(d,J＝7.7Hz,1H),5.03(dd,J＝13.3,5.0Hz,1H),4.72(d,J＝5.8Hz,2H),4.31(d,J＝17.0Hz,1H),4.18(d,J＝16.9Hz,1H),4.13-4.00(m,4H),2.97-2.84(m,2H),2.58(d,J＝17.3Hz,2H),2.38-2.30(m,2H),2.13-1.99(m,2H),2.00-1.88(m,2H).LCMS(ESI)C₃₁H₃₄N₇O₃ ⁺[M+H]⁺：, calculated 552.27, found 552.3) was prepared according to the procedure of scheme 2.

EXAMPLE 157 preparation of Compound GT-10028

The title compound GT-10028 (23 mg, white solid, yield 48％).¹H NMR(400MHz,DMSO-d6)δ11.19(s,1H),10.93(s,1H),9.36(d,J＝1.2Hz,1H),9.02(d,J＝1.2Hz,1H),8.21(dd,J＝7.7,1.6Hz,2H),7.59-7.55(m,3H),7.45(d,J＝8.4Hz,1H),6.95(s,1H),6.88(d,J＝8.1Hz,1H),5.02(dd,J＝13.3,5.1Hz,1H),4.66(s,2H),4.29(d,J＝16.9Hz,1H),4.16(d,J＝16.9Hz,1H),3.51-3.41(m,4H),3.31-3.25(m,1H),3.18-3.14(m,1H),3.08-2.96(m,1H),2.96-2.83(m,1H),2.58(d,J＝17.2Hz,2H),2.40-2.29(m,1H),2.10(brs,2H),2.00-1.86(m,1H)LCMS(ESI)C₂₉H₃₂N₇O₃ ⁺[M+H]⁺： calculated 526.26, found 526.3) was prepared according to the procedure of scheme 2.

EXAMPLE 158 preparation of Compound GT-10029

The title compound GT-10029 (26 mg, white solid, yield 55％).¹H NMR(400MHz,DMSO-d6)δ10.93(s,1H),9.36(d,J＝1.2Hz,1H),9.02(d,J＝1.2Hz,1H),8.21(dd,J＝7.7,1.6Hz,2H),7.59-7.55(m,3H),7.45(d,J＝8.4Hz,1H),6.95(s,1H),6.88(d,J＝8.1Hz,1H),5.03(dd,J＝13.3,5.0Hz,1H),4.88-4.76(m,1H),4.59-4.45(m,2H),4.31(d,J＝17.0Hz,1H),4.18(d,J＝16.4Hz,1H),3.80(s,1H),3.71-3.53(m,2H),3.34-3.25(m,2H),2.97-2.82(m,2H),2.59(d,J＝17.1Hz,2H),2.40-2.21(m,1H),2.00-1.89(m,1H).LCMS(ESI)C₂₉H₃₀N₇O₃ ⁺[M+H]⁺： calculated 524.24, found 524.3) was prepared according to the procedure of scheme 2.

EXAMPLE 159 preparation of Compound GT-10056

The title compound GT-10056 (23 mg, white solid, yield 48％).¹H NMR(400MHz,DMSO-d6)δ11.06(s,1H),8.04(s,1H),7.59(d,J＝8.3Hz,1H),7.57-7.51(m,3H),7.48(d,J＝5.9Hz,1H),7.46-7.41(m,2H),7.38(d,J＝6.4Hz,1H),7.14(s,1H),7.01(d,J＝8.2Hz,1H),5.03(dd,J＝12.8,5.4Hz,1H),3.45-3.38(m,2H),3.34-3.26(m,4H),3.26-3.15(m,2H),2.91-2.78(m,2H),2.59(s,1H),2.61-2.58(m,1H),2.49-2.39(m,2H),2.01-1.95(m,1H).LCMS(ESI)C₂₉H₃₀N₇O₃ ⁺[M+H]⁺： calculated 524.24, found 524.3) was prepared according to the procedure of scheme 2.

EXAMPLE 160 preparation of Compound GT-10057

The title compound GT-10057 (11 mg, white solid, yield 21％).¹H NMR(400MHz,DMSO-d6)δ11.08(s,1H),8.11(s,1H),7.54(dd,J＝8.3,2.6Hz,4H),7.48(t,J＝6.9Hz,2H),7.42(d,J＝8.3Hz,2H),7.37(t,J＝7.1Hz,2H),5.04(dd,J＝12.7,5.4Hz,1H),3.43-3.40(m,2H),3.26-3.19(m,2H),2.91-2.82(m,2H),2.79-2.70(m,1H),2.57(d,J＝21.0Hz,2H),2.48-2.37(m,2H),2.06-1.93(m,1H).LCMS(ESI)C₃₀H₂₆ClFN₅O₅ ⁺[M+H]⁺： calculated 590.16, found 590.2) was prepared according to the method of scheme 3.

EXAMPLE 161 preparation of Compound GT-10058

The title compound GT-10058 (6 mg, white solid, yield 12％).¹H NMR(400MHz,DMSO-d6)δ11.07(s,1H),8.42(s,1H),7.56-7.51(m,4H),7.48-7.44(m,2H),7.38(d,J＝7.4Hz,2H),6.96(s,1H),6.75(s,1H),5.03(dd,J＝12.8,5.4Hz,1H),3.44-3.40(m,2H),3.26-3.14(m,2H),3.10-2.89(m,2H),2.88-2.79(m,1H),2.59-2.56(m,2H),2.48-2.36(m,2H),2.02-1.95(m,1H).LCMS(ESI)C₃₀H₂₆ClFN₅O₅ ⁺[M+H]⁺： calculated 590.16, found 590.2) was prepared according to the method of scheme 3.

EXAMPLE 162 preparation of Compound GT-10059

The title compound GT-10059 (7 mg, white solid, yield 13％).¹H NMR(400MHz,DMSO-d6)δ11.09(s,1H),8.07(s,1H),7.52(d,J＝8.2Hz,1H),7.41-7.35(m,3H),7.24(d,J＝8.4Hz,2H),5.04(dd,J＝12.8,5.4Hz,1H),3.31-3.15(m,4H),2.94-2.81(m,2H),2.60-2.55(m,2H),2.40-2.21(m,3H),2.21-2.06(m,2H),2.06-1.85(m,3H),1.57-1.38(m,2H),0.99(d,J＝9.2Hz,6H).LCMS(ESI)C₃₂H₃₄ClFN₅O₅ ⁺[M+H]⁺： calculated 622.22, found 622.3) was prepared according to the method of scheme 3.

Example 163 preparation of Compound GT-10060

The title compound GT-10060 (14 mg, white solid, yield 26％).¹H NMR(400MHz,DMSO-d6)δ11.08(s,1H),8.37(s,1H),7.40(d,J＝8.5Hz,2H),7.28-7.24(m,2H),6.94(s,1H),6.75(s,1H),5.03(dd,J＝12.7,5.4Hz,1H),3.31-3.13(m,4H),3.01-2.74(m,3H),2.57(d,J＝18.6Hz,2H),2.37-2.33(m,3H),2.22-2.06(m,1H),2.04-1.78(m,3H),1.51-1.41(m,2H),0.98(d,J＝11.1Hz,6H).LCMS(ESI)C₃₂H₃₄ClFN₅O₅ ⁺[M+H]⁺： calculated 622.22, found 622.2) was prepared according to the method of scheme 3.

EXAMPLE 164 preparation of Compound GT-10061

The title compound GT-10061 (20 mg, white solid, yield 38％).¹H NMR(400MHz,DMSO-d6)δ10.94(s,1H),9.29(s,1H),7.50(d,J＝7.9Hz,2H),7.44(d,J＝8.3Hz,1H),7.19(d,J＝8.1Hz,2H),6.94(s,1H),6.90(d,J＝8.4Hz,1H),5.03(dd,J＝13.2,5.0Hz,1H),4.30(d,J＝16.8Hz,1H),4.17(d,J＝17.0Hz,1H),3.61(s,2H),3.28-3.11(m,3H),3.03(brs,2H),2.97-2.84(m,2H),2.59(d,J＝17.7Hz,2H),2.36-2.31(m,2H),2.13(s,4H),2.02(d,J＝17.3Hz,2H),2.01-1.88(m,2H),1.48(s,2H),0.97(s,6H).LCMS(ESI)C₃₄H₄₁ClN₅O₃ ⁺[M+H]⁺： calculated 602.29, found 602.4) was prepared according to the procedure of scheme 1.

Example 165 preparation of Compound GT-10062

The title compound GT-10062 (9 mg, white solid, yield 17％).¹H NMR(400MHz,DMSO-d6)δ11.09(s,1H),8.43(s,1H),7.54(d,J＝8.1Hz,1H),7.47-7.43(m,3H),7.16(d,J＝9.2Hz,2H),5.05(dd,J＝12.7,5.4Hz,1H),3.60(s,2H),3.18-3.13(m,3H),3.05-2.81(m,5H),2.55(d,J＝4.7Hz,2H),2.38-2.27(m,2H),2.10-1.93(m,4H),1.54-1.42(m,2H),0.97(s,6H)LCMS(ESI)C₃₂H₃₆ClFN₅O₄ ⁺[M+H]⁺： calculated 608.24, found 608.3) was prepared according to the procedure of scheme 1.

EXAMPLE 166 preparation of Compound GT-10063

The title compound GT-10063 (12 mg, white solid, yield 23％).¹H NMR(400MHz,DMSO-d6)δ11.08(s,1H),9.97(s,1H),8.81(s,1H),7.47(d,J＝8.3Hz,2H),7.16(d,J＝8.2Hz,2H),7.00(s,1H),6.82(s,1H),5.04(dd,J＝12.8,5.4Hz,1H),3.61(s,2H),3.19-3.06(m,2H),3.06-2.93(m,4H),2.92-2.78(m,2H),2.55(d,J＝4.8Hz,2H),2.33(s,2H),2.10-1.95(m,4H),1.47(t,J＝6.6Hz,2H),0.97(s,6H).LCMS(ESI)C₃₂H₃₆ClFN₅O₄ ⁺[M+H]⁺： calculated 608.24, found 608.3) was prepared according to the method of scheme 1.

EXAMPLE 167 preparation of Compound GT-10065

The title compound GT-10065 (17 mg, white solid, yield 32％).¹H NMR(400MHz,DMSO-d6)δ10.97(s,1H),7.52-7.46(m,2H),7.46-7.41(m,1H),7.21(d,J＝8.4Hz,2H),7.17(s,1H),6.69(d,J＝8.1Hz,1H),5.06(dd,J＝13.1,5.1Hz,1H),4.30(d,J＝16.7Hz,1H),4.18(d,J＝16.6Hz,1H),3.76-3.60(m,3H),3.00-2.80(m,5H),2.65-2.55(m,2H),2.45-2.41(m,2H),2.33-2.27(m,4H),2.05(s,2H),2.02-1.97(m,2H),1.48(t,J＝6.3Hz,3H),0.98(s,6H).LCMS(ESI)C₃₄H₄₁ClN₅O₃ ⁺[M+H]⁺： calculated 602.29, found 602.4) was prepared according to the procedure of scheme 1.

EXAMPLE 168 preparation of Compound GT-10066

The title compound GT-10066 (14 mg, white solid, yield 26％).¹H NMR(400MHz,DMSO-d6)δ10.93(s,1H),7.48-7.43(m,4H),7.23(d,J＝8.3Hz,2H),6.93(s,1H),5.02(dd,J＝13.2,4.9Hz,1H),4.28(d,J＝17.0Hz,1H),4.15(d,J＝17.0Hz,1H),3.79(s,2H),3.55(d,J＝4.8Hz,2H),3.19(d,J＝11.4Hz,2H),2.92-2.87(m,2H),2.63-2.54(m,2H),2.41-2.31(m,3H),2.10(s,2H),2.04-1.91(m,3H),1.50(t,J＝5.9Hz,2H),1.31-1.25(m,2H),0.98(s,6H).LCMS(ESI)C₃₄H₄₁ClN₅O₃ ⁺[M+H]⁺： calculated 602.29, found 602.3) was prepared according to the method of scheme 1.

EXAMPLE 169 preparation of Compound GT-10067

The title compound GT-10067 (16 mg, white solid, yield 31％).¹H NMR(400MHz,DMSO-d6)δ10.93(s,1H),7.47-7.42(m,3H),7.21(d,J＝8.3Hz,2H),6.88(s,1H),6.81(d,J＝7.5Hz,1H),5.02(dd,J＝13.3,5.1Hz,1H),4.29(d,J＝17.0Hz,1H),4.15(d,J＝16.9Hz,1H),4.00-3.87(m,2H),3.67(d,J＝5.6Hz,2H),3.63-3.50(m,4H),3.35-3.24(m,2H),2.97-2.84(m,1H),2.60(s,1H),2.55-2.51(m,2H),2.37-2.30(m,1H),2.18(brs,2H),2.05(brs,2H),1.99-1.87(m,2H),1.63-1.56(m,1H),1.50-1.38(m,2H),0.96(s,6H).LCMS(ESI)C₃₅H₄₃ClN₅O₃ ⁺[M+H]⁺： calculated 616.30, found 616.4) was prepared according to the procedure of scheme 1.

EXAMPLE 170 preparation of Compound GT-10068

The title compound GT-10068 (14 mg, white solid, yield 26％).¹H NMR(400MHz,DMSO-d6)δ10.94(s,1H),9.93(s,1H),7.47(d,J＝8.4Hz,2H),7.43(d,J＝8.3Hz,1H),7.17(d,J＝8.4Hz,2H),6.86(s,1H),6.79(d,J＝7.9Hz,1H),5.02(dd,J＝13.1,5.2Hz,1H),4.29(d,J＝16.8Hz,1H),4.15(d,J＝16.8Hz,1H),3.60(s,2H),3.18-3.02(m,3H),2.93-2.80(m,4H),2.59(d,J＝17.4Hz,2H),2.40-2.22(m,4H),2.05(s,2H),2.00-1.83(m,2H),1.78-1.65(m,1H),1.47(t,J＝6.2Hz,2H),0.96(s,6H).LCMS(ESI)C₃₃H₄₁ClN₅O₃ ⁺[M+H]⁺： calculated 590.29, found 590.3) was prepared according to the method of scheme 1.

EXAMPLE 171 preparation of Compound GT-10069

The title compound GT-10069 (16 mg, white solid, yield 30％).¹H NMR(400MHz,DMSO-d6)δ10.93(s,1H),7.72(s,1H),7.47(d,J＝8.4Hz,2H),7.19(d,J＝8.4Hz,1H),6.93(s,1H),6.84(d,J＝7.5Hz,1H),5.03(dd,J＝12.6,5.7Hz,1H),4.30(d,J＝16.8Hz,1H),4.16(d,J＝17.0Hz,1H),3.71-3.66(m,1H),3.55-3.43(m,2H),3.32-3.13(m,4H),3.01-2.84(m,2H),2.63-2.53(m,2H),2.44-2.20(m,4H),2.13-2.01(m,2H),2.01-1.93(m,1H),1.51-1.41(m,2H),0.99(s,3H),0.97(s,3H).LCMS(ESI)C₃₃H₃₉ClN₅O₃ ⁺[M+H]⁺： calculated 588.27, found 588.3) was prepared according to the method of scheme 1.

EXAMPLE 172 preparation of Compound GT-10070

The title compound GT-10070 (14 mg, white solid, yield 28％).¹H NMR(400MHz,DMSO-d6)δ11.07(s,1H),8.69(d,J＝7.7Hz,1H),8.17(d,J＝7.9Hz,1H),8.07(s,1H),7.63(d,J＝8.4Hz,1H),7.22(s,1H),7.08(s,1H),5.05(dd,J＝13.0,5.3Hz,1H),4.74(s,1H),4.42-4.10(m,1H),3.81(brs,2H),3.76-3.65(m,2H),3.56(s,4H),3.13-2.95(m,2H),2.97-2.85(m,2H),2.58(d,J＝16.2Hz,2H),2.07-1.87(m,4H).LCMS(ESI)C₂₉H₃₀N₉O₆ ⁺[M+H]⁺： calculated 600.23, found 600.3) was prepared according to the procedure of scheme 3.

EXAMPLE 173 preparation of Compound GT-10124

The title compound GT-10124 (15 mg, white solid, yield 31％).¹H NMR(400MHz,DMSO-d6)δ9.11(s,1H),9.02-8.95(m,3H),8.89-8.84(m,2H),8.47(d,J＝8.1Hz,1H),8.40(s,1H),7.63(d,J＝8.4Hz,1H),7.10(d,J＝7.8Hz,1H),5.10(dd,J＝13.3,5.1Hz,1H),4.75(s,2H),4.48-4.41(m,2H),3.90(s,1H),3.75-3.52(m,4H),3.22-3.17(m,2H),2.93-2.82(m,2H),2.82-2.72(m,1H),2.50-2.31(m,3H),2.20-2.10(m,1H).LCMS(ESI)C₃₀H₃₂N₇O₃ ⁺[M+H]⁺： calculated 538.26, found 538.3) was prepared according to the procedure of scheme 2.

EXAMPLE 174 preparation of Compound GT-10125

The title compound GT-10125 (19 mg, white solid, yield 40％).¹H NMR(400MHz,DMSO-d6)δ9.13(s,1H),9.00(d,J＝6.9Hz,2H),8.85(d,J＝6.9Hz,2H),8.47(d,J＝1.3Hz,2H),7.57(d,J＝8.4Hz,1H),7.02(s,1H),6.95(d,J＝8.2Hz,1H),5.08(dd,J＝13.3,5.1Hz,1H),4.51(s,2H),4.38(d,J＝9.0Hz,2H),4.10(s,3H),3.23(d,J＝12.3Hz,2H),3.19-3.08(m,3H),2.94(d,J＝12.3Hz,1H),2.87(dd,J＝13.3,5.3Hz,1H),2.80-2.73(m,1H),2.39-2.33(m,1H),2.18-2.09(m,2H).LCMS(ESI)C₃₀H₃₂N₇O₃ ⁺[M+H]⁺： calculated 538.26, found 538.3) was prepared according to the procedure of scheme 2.

EXAMPLE 175 preparation of Compound GT-10126

The title compound GT-10126 (15 mg, white solid, yield 32％).¹H NMR(400MHz,DMSO-d6)δ9.06(d,J＝1.9Hz,1H),8.99(d,J＝6.9Hz,2H),8.83(d,J＝6.9Hz,2H),8.44(d,J＝8.1Hz,1H),8.35(dd,J＝8.2,2.2Hz,1H),7.75(dd,J＝8.3,4.3Hz,1H),7.47(d,J＝7.0Hz,1H),7.33-7.29(m,1H),5.13(dd,J＝13.4,5.0Hz,1H),4.70(s,2H),4.53(d,J＝11.5Hz,1H),4.48(dd,J＝9.8,2.2Hz,2H),4.32-4.29(m,1H),4.20(s,1H),4.01(s,3H),3.58-3.42(m,4H),2.92-2.84(m,1H),2.83-2.72(m,1H),2.37-2.32(m,3H),2.22-2.15(m,1H).LCMS(ESI)C₃₁H₃₄N₇O₃ ⁺[M+H]⁺： calculated 552.27, found 552.3) was prepared according to the procedure of scheme 2.

EXAMPLE 176 preparation of Compound GT-10127

The title compound GT-10127 (10 mg, white solid, yield 21％).¹H NMR(400MHz,DMSO-d6)δ9.10(d,J＝1.5Hz,1H),8.99(d,J＝6.8Hz,2H),8.89-8.83(m,2H),8.46(d,J＝8.2Hz,1H),8.44-8.38(m,1H),7.59-7.51(m,1H),7.08(s,1H),6.96(d,J＝8.4Hz,1H),5.08(dd,J＝13.3,5.1Hz,1H),4.67(s,2H),4.38(d,J＝8.2Hz,2H),3.61(s,4H),3.46-3.37(m,2H),3.28-3.24(m,1H),3.17-3.06(m,2H),2.91-2.84(m,1H),2.82-2.72(m,1H),2.46(dd,J＝13.2,4.7Hz,1H),2.38(dd,J＝12.3,6.8Hz,1H),2.14-2.07(m,1H).LCMS(ESI)C₂₉H₃₂N₇O₃ ⁺[M+H]⁺： calculated 526.26, found 526.3) was prepared according to the procedure of FIG. 2.

EXAMPLE 177 preparation of Compound GT-10128

The title compound GT-10128 (13 mg, white solid, yield 27％).¹H NMR(400MHz,DMSO-d6)δ9.12(s,1H),8.99(d,J＝6.8Hz,2H),8.85(d,J＝6.3Hz,2H),8.46(s,2H),7.55(d,J＝8.4Hz,1H),7.07(s,1H),6.97(d,J＝8.5Hz,1H),5.06(dd,J＝13.3,5.1Hz,1H),4.59-4.51(m,1H),4.43(t,J＝8.4Hz,1H),4.41-4.34(m,2H),3.76(d,J＝10.3Hz,1H),3.70(d,J＝14.4Hz,1H),3.63(d,J＝12.9Hz,1H),3.43(d,J＝11.9Hz,1H),2.92-2.85(m,2H),2.82-2.65(m,2H),2.51-2.44(m,3H),2.20-2.09(m,1H).LCMS(ESI)C₂₉H₃₀N₇O₃ ⁺[M+H]⁺： calculated 524.24, found 524.3) was prepared according to the procedure of scheme 2.

EXAMPLE 178 preparation of Compound GT-10129

The title compound GT-10129 (11 mg, white solid, yield 23％).¹H NMR(400MHz,DMSO-d6)δ9.12(s,1H),8.99(d,J＝6.8Hz,2H),8.85(d,J＝6.3Hz,2H),8.46(s,2H),7.55(d,J＝8.4Hz,1H),7.07(s,1H),6.97(d,J＝8.5Hz,1H),5.08(dd,J＝13.3,5.1Hz,1H),4.42(s,2H),4.40-4.30(m,4H),3.77(s,1H),2.87(dd,J＝13.4,5.2Hz,1H),2.82-2.73(m,1H),2.54-2.41(m,3H),2.39-2.31(m,2H),2.20-2.09(m,2H).LCMS(ESI)C₂₉H₃₀N₇O₃ ⁺[M+H]⁺： calculated 524.24, found 524.3) was prepared according to the procedure of FIG. 2.

Example 179 preparation of Compound GT-10130

The title compound GT-10130 (10 mg, white solid, yield 20％).¹H NMR(400MHz,DMSO-d6)δ7.79(d,J＝8.3Hz,2H),7.71-7.63(m,4H),7.55(d,J＝8.9Hz,1H),7.48(d,J＝8.5Hz,2H),6.95-6.91(m,2H),5.03(dd,J＝13.3,5.1Hz,1H),4.56(s,2H),4.31(s,2H),3.87-3.82(m,2H),3.13-3.05(m,4H),3.01 2.98(m,2H),2.92-2.83(m,1H),2.78(dd,J＝10.1,7.5Hz,1H),2.72-2.57(m,1H),2.36(dd,J＝13.1,4.9Hz,1H),2.12-2.03(m,1H).LCMS(ESI)C₃₂H₃₃ClN₅O₃ ⁺[M+H]⁺： calculated 570.23, found 570.3) was prepared according to the procedure of scheme 1.

EXAMPLE 180 preparation of Compound GT-10131

The title compound GT-10131 (15 mg, white solid, yield 30％).¹H NMR(400MHz,MeOD)δ7.78(d,J＝8.2Hz,2H),7.68-7.64(m,4H),7.58(d,J＝8.3Hz,1H),7.48(d,J＝8.6Hz,2H),7.03(s,1H),6.97(d,J＝8.8Hz,1H),5.09(dd,J＝13.3,5.1Hz,1H),4.38-4.33(m,4H),4.06(s,2H),3.26-3.22(m,2H),3.21-3.16(m,2H),3.01-2.97(m,2H),2.79-2.75(m,1H),2.52-2.48(m,3H),2.42-2.35(m,1H),2.17-2.07(m,1H).LCMS(ESI)C₃₂H₃₃ClN₅O₃ ⁺[M+H]⁺： calculated 570.23, found 570.3) was prepared according to the procedure of scheme 1.

EXAMPLE 181 preparation of Compound GT-10132

The title compound GT-10132 (16 mg, white solid, yield 32％).¹H NMR(400MHz,DMSO-d6)δ7.75(d,J＝8.3Hz,2H),7.64(d,J＝8.6Hz,2H),7.60(d,J＝8.3Hz,2H),7.55(d,J＝8.4Hz,1H),7.47(d,J＝8.6Hz,2H),7.02(s,1H),6.93(dd,J＝8.4,1.6Hz,1H),5.08(dd,J＝13.3,5.2Hz,1H),4.46(s,2H),4.36(d,J＝7.5Hz,2H),4.08(d,J＝10.9Hz,2H),4.01(d,J＝10.8Hz,2H),2.94-2.85(m,6H),2.45(dd,J＝13.1,4.7Hz,1H),2.18-2.12(m,1H),2.11-1.95(m,4H).LCMS(ESI)C₃₂H₃₅ClN₅O₃ ⁺[M+H]⁺： calculated 584.24, found 584.3) was prepared according to the procedure of scheme 1.

EXAMPLE 182 preparation of Compound GT-10133

The title compound GT-10133 (24 mg, white solid, yield 47％).¹H NMR(400MHz,DMSO-d6)δ7.77(d,J＝8.3Hz,2H),7.69-7.64(m,4H),7.56(d,J＝8.4Hz,1H),7.51-7.44(m,2H),7.01(s,1H),6.94(d,J＝8.4Hz,1H),5.07(dd,J＝13.4,5.1Hz,1H),4.49(s,2H),4.39-4.32(m,2H),3.60-3.58(m,2H),3.55-3.43(m,2H),3.29-3.24(m,2H),3.17-2.99(m,2H),2.91-2.84(m,1H),2.82-2.71(m,1H),2.45-2.37(m,1H),2.29-2.17(m,1H),2.15-2.05(m,2H).LCMS(ESI)C₃₁H₃₃ClN₅O₃ ⁺[M+H]⁺： calculated 558.23, found 558.3) was prepared according to the procedure of scheme 1.

EXAMPLE 183 preparation of Compound GT-10134

The title compound GT-10134 (21 mg, white solid, yield 42％).¹H NMR(400MHz,DMSO-d6)δ7.77(d,J＝8.2Hz,2H),7.71-7.64(m,4H),7.55(d,J＝8.4Hz,1H),7.48(d,J＝8.6Hz,2H),7.03(s,1H),6.95(d,J＝8.3Hz,1H),5.08(dd,J＝13.4,5.1Hz,1H),4.53(d,J＝13.1Hz,1H),4.43-4.28(m,4H),3.80(s,1H),3.65-3.55(m,1H),3.34-3.31(m,2H),3.17-3.05(m,1H),2.93-2.83(m,1H),2.82-2.69(m,1H),2.51-2.44(m,1H),2.41(s,2H),2.20-2.09(m,1H).LCMS(ESI)C₃₁H₃₁ClN₅O₃ ⁺[M+H]⁺： calculated 556.21, found 556.3) was prepared according to the procedure described in scheme 1.

EXAMPLE 184 preparation of Compound GT-10135

The title compound GT-10135 (21 mg, white solid, yield 45％).¹H NMR(400MHz,DMSO-d6)δ7.60-7.50(m,2H),7.34(s,2H),6.98-6.91(m,2H),6.73(d,J＝3.4Hz,1H),6.53(dd,J＝3.4,1.9Hz,1H),5.07(dd,J＝13.2,5.1Hz,1H),4.77(s,2H),4.37-4.22(m,2H),3.91-3.86(m,2H),3.63-3.48(m,1H),3.23-3.04(m,4H),3.05-2.97(m,2H),2.88(dd,J＝12.9,4.9Hz,1H),2.82-2.72(m,1H),2.69-2.63(m,1H),2.41(dd,J＝13.2,4.6Hz,1H),2.20-2.05(m,1H).LCMS(ESI)C₂₈H₃₀N₅O₄S⁺[M+H]⁺： calculated 532.20, found 532.3) was prepared according to the procedure of scheme 1.

EXAMPLE 185 preparation of Compound GT-10136

The title compound GT-10136 (16 mg, white solid, yield 34％).¹H NMR(400MHz,DMSO-d6)δ7.58(d,J＝8.4Hz,1H),7.55(d,J＝1.4Hz,1H),7.35(d,J＝3.8Hz,1H),7.31(d,J＝3.7Hz,1H),7.02(s,1H),6.96(d,J＝8.3Hz,1H),6.71(d,J＝3.4Hz,1H),6.53(dd,J＝3.4,1.9Hz,1H),5.09(dd,J＝13.3,5.1Hz,1H),4.52(s,2H),4.45-4.30(m,2H),4.08(s,2H),3.20(d,J＝11.2Hz,2H),3.01(d,J＝12.3Hz,2H),2.91-2.83(m,1H),2.81-2.69(m,1H),2.50-2.37(m,5H),2.18-2.12(m,1H).LCMS(ESI)C₂₈H₃₀N₅O₄S⁺[M+H]⁺： calculated 532.20, found 532.3) was prepared according to the procedure of scheme 1.

EXAMPLE 186 preparation of Compound GT-10137

The title compound GT-10137 (21 mg, white solid, yield 45％).¹H NMR(400MHz,DMSO-d6)δ7.59(d,J＝8.4Hz,1H),7.55-7.52(m,1H),7.29(s,2H),7.09(s,1H),6.98(dd,J＝8.4,1.6Hz,1H),6.69(d,J＝3.4Hz,1H),6.53(dd,J＝3.4,1.9Hz,1H),5.09(dd,J＝13.3,5.1Hz,1H),4.65(s,2H),4.38(q,J＝17.0Hz,2H),4.12-4.03(m,4H),2.99-2.82(m,4H),2.80-2.70(m,1H),2.51-2.40(m,1H),2.18-2.00(m,6H).LCMS(ESI)C₂₉H₃₂N₅O₄S⁺[M+H]⁺： calculated 546.22, found 546.3) was prepared according to the procedure of scheme 1.

EXAMPLE 187 preparation of Compound GT-10138

The title compound GT-10138 (16 mg, white solid, yield 34％).¹H NMR(400MHz,DMSO-d6)δ7.58-7.53(m,2H),7.34(d,J＝3.8Hz,1H),7.31(d,J＝3.8Hz,1H),7.01(s,1H),6.93(d,J＝8.3Hz,1H),6.72(d,J＝3.4Hz,1H),6.53(dd,J＝3.4,1.9Hz,1H),5.08(dd,J＝13.3,5.2Hz,1H),4.68(s,2H),4.41-4.31(m,2H),3.67-3.61(m,2H),3.56-3.45(m,2H),3.30-3.23(m,2H),3.13-3.02(m,2H),2.93-2.83(m,1H),2.82-2.71(m,1H),2.43-2.39(m,1H),2.27-2.01(m,3H).LCMS(ESI)C₂₇H₃₀N₅O₄S⁺[M+H]⁺： calculated 520.20, found 520.3) was prepared according to the procedure of scheme 1.

EXAMPLE 188 preparation of Compound GT-10139

The title compound GT-10139 (23 mg, white solid, yield 49％).¹H NMR(400MHz,DMSO-d6)δ7.58-7.54(m,2H),7.35(d,J＝3.7Hz,1H),7.30(d,J＝3.7Hz,1H),7.04(s,1H),6.95(d,J＝8.4Hz,1H),6.71(d,J＝3.3Hz,1H),6.53(dd,J＝3.4,1.8Hz,1H),5.08(dd,J＝13.2,5.4Hz,1H),4.71(d,J＝14.0Hz,1H),4.57(d,J＝14.1Hz,1H),4.40-4.34(m,3H),3.80(s,1H),3.75(s,1H),3.58-3.44(m,1H),3.37(d,J＝9.9Hz,1H),3.21-3.09(m,1H),2.86(dd,J＝13.3,5.1Hz,1H),2.76(d,J＝17.3Hz,1H),2.53-2.29(m,3H),2.20-2.05(m,1H).LCMS(ESI)C₂₇H₂₈N₅O₄S⁺[M+H]⁺： calculated 518.19, found 518.2) was prepared according to the procedure described in scheme 1.

EXAMPLE 189 preparation of Compound GT-10141

The title compound GT-10141 (15 mg, white solid, yield 40％).¹H NMR(400MHz,DMSO-d6)δ7.72(dd,J＝7.0,2.0Hz,1H),7.63-7.59(m,2H),7.56(d,J＝8.5Hz,2H),7.44(dd,J＝5.2,1.9Hz,1H),7.41(d,J＝8.5Hz,2H),6.90(d,J＝10.3Hz,1H),6.79(s,1H),6.75(dd,J＝8.4,1.8Hz,1H),5.12(dd,J＝13.4,5.2Hz,1H),4.55(s,2H),4.45-4.33(m,3H),3.67(dd,J＝11.3,7.9Hz,2H),3.26-3.17(m,1H),3.01(d,J＝9.5Hz,1H),2.87-2.83(m,1H),2.83-2.75(m,1H),2.74-2.64(m,3H),2.61-2.54(m,2H),2.48(dd,J＝13.1,4.7Hz,1H),2.23-2.13(m,1H).LCMS(ESI)C₃₂H₃₃ClN₅O₃ ⁺[M+H]⁺： calculated 570.23, found 570.3) was prepared according to the procedure of scheme 1.

EXAMPLE 190 preparation of Compound GT-10142

The title compound GT-10142 (19 mg, white solid, yield 51％).¹H NMR(400MHz,DMSO-d6)δ7.86(s,1H),7.80(dt,J＝7.5,1.5Hz,1H),7.69(d,J＝8.5Hz,2H),7.65-7.53(m,3H),7.51-7.46(m,2H),6.97-6.90(m,2H),5.09(dd,J＝13.2,5.2Hz,1H),4.58(s,2H),4.31(s,2H),3.85(dd,J＝11.0,7.9Hz,2H),3.16-3.04(m,4H),3.02-2.94(m,2H),2.88(dd,J＝13.4,5.1Hz,1H),2.82-2.73(m,1H),2.68-2.64(m,2H),2.45-2.30(m,1H),2.19-2.08(m,1H).LCMS(ESI)C₃₂H₃₃ClN₅O₃ ⁺[M+H]⁺： calculated 570.23, found 570.3) was prepared according to the procedure of scheme 1.

EXAMPLE 191 preparation of Compound GT-10143

The title compound GT-10143 (12 mg, white solid, yield 33％).¹H NMR(400MHz,DMSO-d6)δ7.55(d,J＝8.3Hz,1H),7.24-7.16(m,5H),6.76(s,1H),5.12(dd,J＝13.5,5.1Hz,1H),4.39-4.30(m,2H),3.84(dd,J＝11.3,8.0Hz,2H),3.77(s,2H),3.65(s,1H),3.45-3.37(m,1H),3.06(d,J＝9.1Hz,1H),3.00-2.88(m,4H),2.84-2.75(m,1H),2.62-2.57(m,4H),2.46(dd,J＝13.1,4.8Hz,1H),2.37(brs,3H),2.29(brs,3H),2.23-2.12(m,1H).LCMS(ESI)C₃₂H₃₇FN₅O₃ ⁺[M+H]⁺： calculated 558.29, found 558.3) was prepared according to the procedure of scheme 1.

EXAMPLE 192 preparation of Compound GT-10144

The title compound GT-10144 (14 mg, white solid, yield 37％).¹H NMR(400MHz,DMSO-d6)δ7.58(d,J＝8.4Hz,1H),7.49(d,J＝8.3Hz,2H),7.29(d,J＝8.2Hz,2H),6.81(s,1H),6.78(d,J＝8.5Hz,1H),5.11(dd,J＝13.2,5.1Hz,1H),4.41-4.35(m,4H),3.94(t,J＝5.4Hz,2H),3.91-3.84(m,3H),3.36(brs,1H),3.21-3.13(m,1H),2.99-2.94(m,3H),2.81(brs,1H),2.78-2.69(m,1H),2.68-2.58(m,3H),2.54-2.43(m,4H),2.19-2.13(m,1H).LCMS(ESI)C₃₁H₃₅ClN₅O₄ ⁺[M+H]⁺： calculated 576.24, found 576.3) was prepared according to the procedure of scheme 1.

EXAMPLE 193 preparation of Compound GT-10145

The title compound GT-10145 (11 mg, white solid, yield 30％).¹H NMR(400MHz,DMSO-d6)δ7.55(d,J＝8.4Hz,1H),7.31(d,J＝8.8Hz,2H),7.22(d,J＝8.8Hz,2H),6.79(s,1H),6.76(d,J＝8.5Hz,1H),5.12(dd,J＝13.2,5.0Hz,1H),4.39-4.33(m,4H),3.94(t,J＝5.4Hz,2H),3.87-3.83(m,3H),3.36(d,J＝5.2Hz,1H),3.14(d,J＝9.5Hz,1H),2.96-2.87(m,3H),2.81-2.78(m,2H),2.68-2.56(m,3H),2.54-2.42(m,4H),2.22-2.11(m,1H).LCMS(ESI)C₃₁H₃₅FN₅O₄ ⁺[M+H]⁺： calculated 560.27, found 560.3) was prepared according to the procedure of scheme 1.

EXAMPLE 194 preparation of Compound GT-10146

The title compound GT-10146 (20 mg, white solid, yield 50％).¹H NMR(400MHz,DMSO-d6)δ7.58(d,J＝8.3Hz,1H),7.49(d,J＝8.4Hz,2H),7.26(d,J＝8.3Hz,2H),6.78(s,1H),6.76(d,J＝8.4Hz,1H),5.11(dd,J＝13.2,5.2Hz,1H),4.42-4.32(m,4H),3.89(s,2H),3.83(dd,J＝11.2,7.6Hz,2H),3.36(brs,1H),3.06(d,J＝8.8Hz,1H),2.95-2.92(m,3H),2.83-2.73(m,1H),2.68-2.55(m,4H),2.47(dd,J＝13.2,4.6Hz,1H),2.39-2.36(m,2H),2.20-2.15(m,1H),1.32(s,6H).LCMS(ESI)C₃₃H₃₉ClN₅O₄ ⁺[M+H]⁺： calculated 604.27, found 604.3) was prepared according to the procedure of scheme 1.

EXAMPLE 195 preparation of Compound GT-10147

The title compound GT-10147 (16 mg, white solid, yield 40％).¹H NMR(400MHz,DMSO-d6)δ7.58(d,J＝8.0Hz,1H),7.50(d,J＝8.5Hz,2H),7.25(d,J＝8.3Hz,2H),6.76-6.74(m,2H),5.12(dd,J＝13.2,5.1Hz,1H),4.38(t,J＝10.0Hz,3H),3.88-3.84(m,3H),3.37(d,J＝6.3Hz,1H),3.04(d,J＝8.5Hz,1H),2.96-2.93(m,4H),2.90-2.77(m,4H),2.68-2.61(m,5H),2.50-2.43(m,1H),2.32-2.21(m,2H),2.21-2.11(m,1H).LCMS(ESI)C₃₂H₃₅ClFN₅O₃ ⁺[M+H]⁺： calculated 610.24, found 610.3) was prepared according to the procedure of scheme 1.

EXAMPLE 196 preparation of Compound GT-10148

The title compound GT-10148 (13 mg, white solid, yield 32％).¹H NMR(400MHz,DMSO-d6)δ7.58(d,J＝8.4Hz,1H),7.46(d,J＝8.5Hz,2H),7.22(d,J＝8.4Hz,2H),6.78(s,1H),6.76(d,J＝8.4Hz,1H),5.12(dd,J＝13.2,5.1Hz,1H),4.42-4.32(m,2H),3.87-3.81(m,2H),3.77(s,2H),3.35-3.31(m,1H),3.29(s,3H),3.17-3.08(m,1H),2.97-2.93(m,3H),291-2.88(m,2H),2.81-2.71(m,3H),2.66-2.54(m,3H),2.50-2.45(m,1H),2.35-2.31(m,2H),2.22-2.13(m,1H),2.05-2.00(m,1H),1.80-1.71(m,1H),1.34(s,3H).LCMS(ESI)C₃₄H₄₁ClN₅O₄ ⁺[M+H]⁺： calculated 618.28, found 618.3) was prepared according to the procedure of scheme 1.

Example 197 preparation of Compound GT-10149

The title compound GT-10149 (7 mg, white solid, yield 19％).¹H NMR(400MHz,DMSO-d6)δ7.54(d,J＝8.3Hz,1H),7.24-7.13(m,5H),6.77-6.74(m,1H),5.12(dd,J＝13.4,5.2Hz,1H),4.35-4.32(m,2H),3.86-3.76(m,3H),3.26(dd,J＝11.8,6.4Hz,1H),3.02-2.97(m,4H),2.85-2.77(m,1H),2.63-2.55(m,4H),2.49-2.41(m,1H),2.33(brs,3H),2.19-2.12(m,3H),1.64-1.58(m,2H),1.05(s,6H).LCMS(ESI)C₃₄H₄₁FN₅O₃ ⁺[M+H]⁺： calculated 586.32, found 586.4) was prepared according to the procedure of scheme 1.

EXAMPLE 198 preparation of Compound GT-10232

The title compound GT-10232 (28 mg, white solid, yield 74％).¹H NMR(400MHz,MeOD)δ7.88-7.79(m,1H),7.63-7.51(m,5H),7.47-7.38(m,3H),6.94(s,1H),6.88(d,J＝8.4Hz,1H),5.07(dd,J＝13.6,5.0Hz,1H),4.42-4.28(m,4H),3.82(s,2H),3.05(d,J＝12.8Hz,2H),2.95(d,J＝12.5Hz,2H),2.86(dd,J＝13.2,5.1Hz,1H),2.80-2.69(m,1H),2.43(dd,J＝13.1,5.0Hz,1H),2.22-2.06(m,3H),1.57-1.44(m,2H).LCMS(ESI)C₃₂H₃₃ClN₅O₃ ⁺[M+H]⁺： calculated 570.23, found 570.3) was prepared according to the procedure of scheme 1.

Example 199 preparation of Compound GT-10233

The title compound GT-10233 (27 mg, white solid, yield 72％).¹H NMR(400MHz,MeOD)δ7.90(s,1H),7.78(s,1H),7.72-7.64(m,2H),7.61-7.56(m,3H),7.48(dd,J＝8.5,1.6Hz,2H),7.02(s,1H),6.95(d,J＝8.1Hz,1H),5.08(dd,J＝13.1,3.7Hz,1H),4.44-4.26(m,4H),4.04(s,2H),3.16(d,J＝11.6Hz,2H),3.06(d,J＝11.9Hz,2H),2.97-2.81(m,1H),2.76(d,J＝17.7Hz,1H),2.56-2.33(m,5H),2.19-2.05(m,1H).LCMS(ESI)C₃₂H₃₃ClN₅O₃ ⁺[M+H]⁺： calculated 570.23, found 570.3) was prepared according to the procedure of scheme 1.

Example 200 preparation of Compound GT-10234

The title compound GT-10234 (12 mg, white solid, yield 32％).¹H NMR(400MHz,MeOD)δ7.55(d,J＝8.4Hz,1H),7.28-7.20(m,2H),7.15(t,J＝8.6Hz,2H),6.96(s,1H),6.90(d,J＝8.4Hz,1H),5.07(dd,J＝13.5,5.2Hz,1H),4.43-4.26(m,2H),3.89(s,2H),3.64(s,2H),3.11-2.98(m,4H),2.91-2.81(m,1H),2.77-2.67(m,1H),2.45-2.35(m,3H),2.31(s,2H),2.23-2.07(m,3H),1.82(s,4H),1.54-1.40(m,2H).LCMS(ESI)C₃₂H₃₇FN₅O₃ ⁺[M+H]⁺： calculated 558.29, found 558.3) was prepared according to the procedure of scheme 1.

EXAMPLE 201 preparation of Compound GT-10235

The title compound GT-10235 (13 mg, white solid, yield 34％).¹H NMR(400MHz,MeOD)δ7.58(d,J＝8.3Hz,1H),7.52(d,J＝8.3Hz,2H),7.34(d,J＝8.3Hz,2H),7.00(s,1H),6.94(d,J＝8.1Hz,1H),5.10(dd,J＝13.3,5.1Hz,1H),4.48-4.27(m,5H),3.97-3.92(m,3H),3.71(s,2H),3.15-3.05(m,4H),2.97-2.85(m,1H),2.76(d,J＝15.7Hz,1H),2.53(s,2H),2.45(dd,J＝13.2,4.5Hz,1H),2.21-2.06(m,3H),1.46-1.44(m,2H).LCMS(ESI)C₃₁H₃₅ClN₅O₄ ⁺[M+H]⁺： calculated 576.24, found 576.3) was prepared according to the procedure of scheme 1.

EXAMPLE 202 preparation of Compound GT-10236

The title compound GT-10236 (12 mg, white solid, yield 32％).¹H NMR(400MHz,MeOD)δ7.54(d,J＝8.3Hz,1H),7.35-7.28(m,2H),7.22-7.17(m,2H),6.95(s,1H),6.89(d,J＝8.4Hz,1H),5.06(dd,J＝13.3,5.1Hz,1H),4.38(s,2H),4.33(d,J＝7.7Hz,2H),3.97-3.89(m,3H),3.72(s,2H),3.19-3.09(m,1H),3.07(s,3H),2.91-2.81(m,1H),2.75(d,J＝17.7Hz,1H),2.51(s,2H),2.46-2.37(m,1H),2.33-2.30(m,1H),2.18-2.05(m,3H),1.45-1.42(m,2H).LCMS(ESI)C₃₁H₃₅FN₅O₄ ⁺[M+H]⁺： calculated 560.27, found 560.3) was prepared according to the procedure of scheme 1.

EXAMPLE 203 preparation of Compound GT-10237

The title compound GT-10237 (12 mg, white solid, yield 30％).¹H NMR(400MHz,MeOD)δ7.55(d,J＝8.4Hz,1H),7.47(d,J＝8.3Hz,2H),7.27(d,J＝8.4Hz,2H),6.95(s,1H),6.89(d,J＝8.4Hz,1H),5.07(dd,J＝13.3,5.1Hz,1H),4.40(s,2H),4.34(d,J＝7.2Hz,2H),3.89(s,2H),3.73(s,2H),3.14-2.97(m,4H),2.92-2.81(m,1H),2.75(d,J＝15.4Hz,1H),2.43(dd,J＝13.2,4.7Hz,1H),2.39(s,2H),2.16-2.11(m,3H),1.51-1.40(m,2H),1.31(s,6H).LCMS(ESI)C₃₃H₃₉ClN₅O₄ ⁺[M+H]⁺： calculated 604.27, found 604.3) was prepared according to the procedure of scheme 1.

EXAMPLE 204 preparation of Compound GT-10238

The title compound GT-10238 (12 mg, white solid, yield 30％).¹H NMR(400MHz,MeOD)δ7.55(d,J＝9.0Hz,1H),7.47(d,J＝7.3Hz,2H),7.26(d,J＝7.6Hz,2H),6.96(s,1H),6.90(d,J＝8.9Hz,1H),5.07(dd,J＝12.4,4.2Hz,1H),4.34(q,J＝17.3Hz,2H),3.91(s,2H),3.69(s,2H),3.15-3.02(m,3H),2.94-2.85(m,3H),2.81-2.60(m,4H),2.52-2.36(m,1H),2.33-2.06(m,5H),1.49-1.38(m,2H).LCMS(ESI)C₃₂H₃₅ClF₂N₅O₃ ⁺[M+H]⁺： calculated 610.24, found 610.3) was prepared according to the procedure of scheme 1.

EXAMPLE 205 preparation of Compound GT-10239

The title compound GT-10239 (8 mg, white solid, yield 20％).¹H NMR(400MHz,MeOD)δ7.56(d,J＝8.5Hz,1H),7.44(d,J＝7.9Hz,2H),7.22(d,J＝8.1Hz,2H),6.96(s,1H),6.90(d,J＝8.4Hz,1H),5.07(dd,J＝13.0,4.7Hz,1H),4.35(q,J＝17.0Hz,2H),3.91(s,2H),3.64(s,2H),3.33(s,3H),3.12-3.01(m,4H),2.86(dd,J＝14.1,5.9Hz,1H),2.76(d,J＝17.3Hz,1H),2.61-2.48(m,1H),2.47-2.29(m,4H),2.21-2.01(m,4H),1.82-1.65(m,1H),1.52-1.40(m,2H),1.35(s,3H).LCMS(ESI)C₃₄H₄₁ClN₅O₄ ⁺[M+H]⁺： calculated 618.28, found 618.3) was prepared according to the procedure of scheme 1.

EXAMPLE 206 preparation of Compound GT-10240

The title compound GT-10240 (9 mg, white solid, yield 20％).¹H NMR(400MHz,MeOD)δ7.55(d,J＝8.3Hz,1H),7.25-7.12(m,4H),6.95(s,1H),6.90(d,J＝7.9Hz,1H),5.07(dd,J＝13.2,5.1Hz,1H),4.41-4.25(m,2H),3.84(s,2H),3.66(s,2H),3.12-3.03(m,3H),2.91-2.84(m,1H),2.80-2.71(m,1H),2.47-2.40(m,1H),2.39-2.34(m,2H),2.32-2.26(m,1H),2.23-2.06(m,5H),1.61(t,J＝6.3Hz,2H),1.52-1.38(m,2H),1.03(s,6H).LCMS(ESI)C₃₄H₃₄₁FN₅O₃ ⁺[M+H]⁺： calculated 586.32, found 586.4) was prepared according to the procedure of scheme 1.

EXAMPLE 207 preparation of Compound GT-10241

The title compound GT-10241 (22 mg, white solid, yield 59％).¹H NMR(400MHz,MeOD)δ7.61-7.57(m,2H),7.56-7.49(m,4H),7.43-7.37(m,3H),7.12(s,1H),7.01(d,J＝8.4Hz,1H),5.08(dd,J＝13.2,5.0Hz,1H),4.49(d,J＝8.3Hz,2H),4.36(t,J＝12.7Hz,2H),4.02(d,J＝10.5Hz,2H),3.74(d,J＝10.7Hz,2H),3.04-2.69(m,6H),2.43-2.40(m,1H),2.18-2.00(m,3H),1.82(s,2H).LCMS(ESI)C₃₃H₃₅ClN₅O₃ ⁺[M+H]⁺： calculated 584.24, found 584.3) was prepared according to the procedure of scheme 1.

EXAMPLE 208 preparation of Compound GT-10242

The title compound GT-10242 (23 mg, white solid, yield 62％).¹H NMR(400MHz,MeOD)δ7.81(s,1H),7.74(d,J＝7.5Hz,1H),7.67(d,J＝8.5Hz,2H),7.64-7.58(m,1H),7.54(dd,J＝14.5,7.7Hz,2H),7.47(d,J＝8.4Hz,2H),7.15(s,1H),7.04(d,J＝7.7Hz,1H),5.08(dd,J＝13.1,4.9Hz,1H),4.50(s,2H),4.39(q,J＝17.3Hz,2H),4.12(d,J＝10.6Hz,2H),4.04(d,J＝10.0Hz,2H),3.13-2.92(m,3H),2.91-2.84(m,2H),2.75(d,J＝15.5Hz,1H),2.44-2.40(m,1H),2.123-2.11(m,5H).LCMS(ESI)C₃₃H₃₅ClN₅O₃ ⁺[M+H]⁺： calculated 584.24, found 584.3) was prepared according to the procedure of scheme 1.

EXAMPLE 209 preparation of Compound GT-10243

The title compound GT-10243 (15 mg, white solid, yield 41％).¹H NMR(400MHz,MeOD)δ7.63(d,J＝8.4Hz,1H),7.28-7.20(m,2H),7.19-7.11(m,3H),7.07(d,J＝7.2Hz,1H),5.09(dd,J＝13.3,5.1Hz,1H),4.40(q,J＝16.9Hz,2H),4.10(d,J＝11.1Hz,2H),3.78(s,2H),3.68(d,J＝11.2Hz,2H),3.06(brs,2H),2.98-2.82(m,3H),2.76(d,J＝17.4Hz,1H),2.46(dd,J＝13.3,4.6Hz,1H),2.36(s,2H),2.16(brs,5H),1.78(brs,6H).LCMS(ESI)C₃₃H₃₉FN₅O₃ ⁺[M+H]⁺： calculated 572.30, found 572.3) was prepared according to the procedure of scheme 1.

EXAMPLE 210 preparation of Compound GT-10244

The title compound GT-10244 (20 mg, white solid, yield 53％).¹H NMR(400MHz,MeOD)δ7.62(d,J＝8.4Hz,1H),7.47(d,J＝8.3Hz,2H),7.28(d,J＝8.3Hz,2H),7.14(s,1H),7.03(d,J＝8.1Hz,1H),5.09(dd,J＝13.2,5.1Hz,1H),4.39(q,J＝17.0Hz,2H),4.23(s,2H),4.10(d,J＝10.8Hz,2H),3.92-3.86(m,4H),3.66(d,J＝11.1Hz,2H),3.11-2.94(m,2H),2.92-2.84(m,2H),2.76(d,J＝15.8Hz,2H),2.54-2.42(m,3H),2.18-2.04(m,3H),1.78(brs,2H).LCMS(ESI)C₃₂H₃₇ClN₅O₄ ⁺[M+H]⁺： calculated 590.25, found 590.3) was prepared according to the procedure of scheme 1.

EXAMPLE 211 preparation of Compound GT-10245

The title compound GT-10245 (17 mg, white solid, yield 46％).¹H NMR(400MHz,MeOD)δ7.65(d,J＝8.4Hz,1H),7.34-7.27(m,2H),7.24-7.16(m,3H),7.08(dd,J＝8.3,1.8Hz,1H),5.09(dd,J＝13.3,5.1Hz,1H),4.41(q,J＝17.1Hz,2H),4.24(s,2H),4.11(d,J＝11.2Hz,2H),3.90(t,J＝5.5Hz,2H),3.87(s,2H),3.67(d,J＝11.1Hz,2H),3.19-3.12(m,2H),2.98-2.92(m,2H),2.87(dd,J＝13.4,5.3Hz,1H),2.82-2.68(m,1H),2.53-2.40(m,3H),2.23-2.08(m,3H),1.82(s,2H).LCMS(ESI)C₃₂H₃₇FN₅O₄ ⁺[M+H]⁺： calculated 574.28, found 574.3) was prepared according to the procedure of scheme 1.

EXAMPLE 212 preparation of Compound GT-10246

The title compound GT-10246 (21 mg, white solid, yield 51％).¹H NMR(400MHz,MeOD)δ7.62(d,J＝8.4Hz,1H),7.47(d,J＝8.5Hz,2H),7.26(d,J＝8.5Hz,2H),7.16(s,1H),7.04(d,J＝8.4Hz,1H),5.09(dd,J＝13.2,5.1Hz,1H),4.39(q,J＝17.0Hz,2H),4.26(s,2H),4.10(d,J＝10.7Hz,2H),3.88(s,2H),3.67(d,J＝10.9Hz,2H),3.02(s,2H),2.96-2.81(m,3H),2.76(d,J＝15.5Hz,1H),2.50-2.41(m,1H),2.34(s,2H),2.19-2.08(m,3H),1.78(s,2H),1.30(s,6H).LCMS(ESI)C₃₄H₄₁ClN₅O₄ ⁺[M+H]⁺： calculated 618.28, found 618.3) was prepared according to the procedure of scheme 1.

EXAMPLE 213 preparation of Compound GT-10247

The title compound GT-10247 (16 mg, white solid, yield 40％).¹H NMR(400MHz,MeOD)δ7.60(d,J＝8.3Hz,1H),7.47(d,J＝7.5Hz,2H),7.25(d,J＝7.6Hz,2H),7.12(s,1H),7.01(d,J＝8.0Hz,1H),5.09(dd,J＝13.2,4.8Hz,1H),4.38(q,J＝17.4Hz,2H),4.11(d,J＝10.7Hz,2H),3.83(s,2H),3.68(d,J＝11.2Hz,2H),3.03-2.82(m,3H),2.82-2.69(m,4H),2.65(s,3H),2.53-2.37(m,1H),2.24-2.01(m,5H),1.75(s,2H).LCMS(ESI)C₃₃H₃₇ClF₂N₅O₃ ⁺[M+H]⁺： calculated 624.25, found 624.3) was prepared according to the procedure of scheme 1.

EXAMPLE 214 preparation of Compound GT-10248

The title compound GT-10248 (14 mg, white solid, yield 35％).¹H NMR(400MHz,MeOD)δ7.61(d,J＝8.3Hz,1H),7.44(d,J＝8.4Hz,2H),7.21(d,J＝8.4Hz,2H),7.14(s,1H),7.03(d,J＝6.9Hz,1H),5.09(dd,J＝13.2,4.9Hz,1H),4.39(q,J＝16.7Hz,2H),4.08(d,J＝10.8Hz,2H),3.77(s,2H),3.67(t,J＝12.1Hz,2H),3.27(s,3H),3.07-2.94(m,2H),2.95-2.69(m,4H),2.53-2.43(m,2H),2.32(d,J＝18.3Hz,1H),2.25(s,2H),2.17-2.09(m,3H),2.02-1.96(m,1H),1.73(s,3H),1.30(s,3H).LCMS(ESI)C₃₅H₄₃ClN₅O₄ ⁺[M+H]⁺： calculated 632.30, found 632.4) was prepared according to the procedure of scheme 1.

EXAMPLE 215 preparation of Compound GT-10249

The title compound GT-10249 (11 mg, white solid, yield 29％).¹H NMR(400MHz,MeOD)δ7.60(d,J＝8.4Hz,1H),7.22-7.14(m,4H),7.11(s,1H),7.01(d,J＝8.3Hz,1H),5.08(dd,J＝13.2,5.1Hz,1H),4.38(q,J＝17.2Hz,2H),4.08(d,J＝11.0Hz,2H),3.80(s,2H),3.65(d,J＝11.1Hz,2H),3.08-2.61(m,6H),2.49-2.40(m,1H),2.20(s,2H),2.14-2.05(m,5H),1.72(s,2H),1.55(t,J＝6.1Hz,2H),1.02(s,6H).LCMS(ESI)C₃₅H₄₃FN₅O₃ ⁺[M+H]⁺： calculated 600.33, found 600.4) was prepared according to the procedure of scheme 1.

EXAMPLE 216 preparation of Compound GT-10251

The title compound GT-10251 (22 mg, white solid, yield 58％).¹H NMR(400MHz,MeOD)δ7.79-7.77(m,1H),7.57-7.54(m,5H),7.43-7.31(m,3H),6.91(s,1H),6.83(d,J＝8.1Hz,1H),5.07(dd,J＝12.5,3.7Hz,1H),4.47(s,2H),4.34(q,J＝17.0Hz,2H),3.43-3.40(m,2H),3.21-3.14(m,2H),3.11-3.01(m,1H),3.01-2.87(m,3H),2.88-2.73(m,2H),2.49-2.40(m,1H),2.20-2.04(m,1H),1.87(s,2H).LCMS(ESI)C₃₁H₃₃ClN₅O₃ ⁺[M+H]⁺： calculated 558.23, found 558.3) was prepared according to the procedure of scheme 1.

EXAMPLE 217 preparation of Compound GT-10252

The title compound GT-10252 (25 mg, white solid, yield 66％).¹H NMR(400MHz,MeOD)δ7.87(s,1H),7.79-7.76(m,1H),7.71-7.67(m,2H),7.63-7.52(m,3H),7.51-7.43(m,2H),7.02(s,1H),6.94(d,J＝6.7Hz,1H),5.07(dd,J＝16.1,3.9Hz,1H),4.52(s,2H),4.42-4.25(m,2H),3.67-3.55(m,2H),3.55-3.43(m,2H),3.37-3.35(m,1H),3.25-3.21(m,2H),3.16-2.98(m,1H),2.87(d,J＝13.8Hz,1H),2.76(d,J＝16.5Hz,1H),2.49-2.35(m,1H),2.25-2.16(m,1H),2.16-2.02(m,2H).LCMS(ESI)C₃₁H₃₃ClN₅O₃ ⁺[M+H]⁺： calculated 558.23, found 558.3) was prepared according to the procedure of scheme 1.

EXAMPLE 218 preparation of Compound GT-10253

The title compound GT-10253 (13 mg, white solid, yield 35％).¹H NMR(400MHz,MeOD)δ7.53(d,J＝8.2Hz,1H),7.25-7.09(m,4H),6.93(s,1H),6.85(d,J＝8.3Hz,1H),5.07(dd,J＝12.8,2.4Hz,1H),4.42-4.26(m,2H),3.71(s,2H),3.57-3.46(m,2H),3.21-3.09(m,3H),3.01-2.84(m,3H),2.85-2.73(m,2H),2.52-2.41(m,1H),2.36(s,2H),2.23(s,2H),2.16-2.09(m,1H),1.99-1.90(m,1H),1.81(brs,5H).LCMS(ESI)C₃₁H₃₇FN₅O₃ ⁺[M+H]⁺： calculated 546.29, found 546.3) was prepared according to the procedure of scheme 1.

EXAMPLE 219 preparation of Compound GT-10254

The title compound GT-10254 (22 mg, white solid, yield 57％).¹H NMR(400MHz,MeOD)δ7.54(d,J＝8.4Hz,1H),7.47(d,J＝8.3Hz,2H),7.24(d,J＝8.4Hz,2H),6.93(s,1H),6.84(d,J＝8.7Hz,1H),5.07(dd,J＝13.5,4.3Hz,1H),4.39-4.31(m,4H),3.92(t,J＝5.4Hz,2H),3.80(s,2H),3.57-3.45(m,2H),3.21-3.08(m,3H),2.97-2.86(m,3H),2.76(d,J＝17.9Hz,1H),2.56-2.34(m,4H),2.16-2.07(m,1H),2.01-1.77(m,2H).LCMS(ESI)C₃₀H₃₅ClN₅O₄ ⁺[M+H]⁺： calculated 564.24, found 564.3) was prepared according to the procedure of scheme 1.

Example 220 preparation of Compound GT-10255

The title compound GT-10255 (20 mg, white solid, yield 54％).¹H NMR(400MHz,MeOD)δ7.53(d,J＝8.4Hz,1H),7.27(dd,J＝8.6,5.4Hz,2H),7.19(t,J＝8.7Hz,2H),6.94(s,1H),6.84(d,J＝8.4Hz,1H),5.07(dd,J＝13.3,5.1Hz,1H),4.40-4.27(m,4H),3.92(t,J＝5.5Hz,2H),3.80(s,2H),3.60-3.43(m,2H),3.21-3.10(m,3H),3.02-2.83(m,4H),2.80-2.71(m,1H),2.53-2.39(m,3H),2.15-2.11(m,1H),1.93(brs,1H),1.85(brs,1H).LCMS(ESI)C₃₀H₃₅FN₅O₄ ⁺[M+H]⁺： calculated 548.27, found 548.3) was prepared according to the procedure of scheme 1.

EXAMPLE 221 preparation of Compound GT-10256

The title compound GT-10256 (23 mg, white solid, yield 57％).¹H NMR(400MHz,MeOD)δ7.54(d,J＝8.5Hz,1H),7.46(d,J＝7.7Hz,2H),7.22(d,J＝7.7Hz,2H),6.94(s,1H),6.85(d,J＝7.6Hz,1H),5.08(dd,J＝12.6,3.9Hz,1H),4.45-4.25(m,4H),3.81(s,2H),3.61-3.43(m,2H),3.24-3.06(m,3H),3.06-2.84(m,4H),2.76(d,J＝17.2Hz,1H),2.52-2.37(m,1H),2.35(s,2H),2.22-2.05(m,1H),1.94(brs,1H),1.87(brs,1H),1.30(s,6H).LCMS(ESI)C₃₂H₃₉ClN₅O₄ ⁺[M+H]⁺： calculated 592.27, found 592.3) was prepared according to the procedure of scheme 1.

EXAMPLE 222 preparation of Compound GT-10257

The title compound GT-10257 (18 mg, white solid, yield 44％).¹H NMR(400MHz,MeOD)δ7.54(d,J＝8.4Hz,1H),7.47(d,J＝8.3Hz,2H),7.20(d,J＝8.3Hz,2H),6.93(s,1H),6.84(d,J＝8.1Hz,1H),5.08(dd,J＝13.1,4.6Hz,1H),4.42-4.25(m,2H),3.76(s,2H),3.61-3.43(m,2H),3.25-3.08(m,3H),3.06-2.74(m,7H),2.67(s,2H),2.46-2.40(m,1H),2.31-2.17(m,2H),2.14-2.10(m,1H),1.95(brs,1H),1.86(brs,1H).LCMS(ESI)C₃₁H₃₅ClF₂N₅O₃ ⁺[M+H]⁺： calculated 598.24, found 598.3) was prepared according to the procedure of scheme 1.

Example 223 preparation of Compound GT-10258

The title compound GT-10258 (11 mg, white solid, yield 27％).¹H NMR(400MHz,MeOD)δ7.53(d,J＝8.1Hz,1H),7.43(d,J＝7.9Hz,2H),7.17(d,J＝8.0Hz,2H),6.94(s,1H),6.85(d,J＝7.1Hz,1H),5.07(dd,J＝13.1,4.6Hz,1H),4.34(q,J＝17.1Hz,3H),3.70(s,2H),3.61-3.48(m,2H),3,21(s,3H),3.18-3.11(m,2H),3.01-2.85(m,4H),2.76(d,J＝15.7Hz,1H),2.53-2.45(m,2H),2.35-2.29(m,4H),2.18-2.11(m,1H),2.05-1.98(m,2H),1.86(brs,1H),1.79-1.71(m,1H),1.32(s,3H).LCMS(ESI)C₃₃H₄₁ClN₅O₄ ⁺[M+H]⁺： calculated 606.28, found 606.3) was prepared according to the procedure of scheme 1.

EXAMPLE 224 preparation of Compound GT-10259

The title compound GT-10259 (16 mg, white solid, yield 41％).¹H NMR(400MHz,MeOD)δ7.53(d,J＝8.0Hz,1H),7.23-7.11(m,4H),6.93(s,1H),6.84(d,J＝7.9Hz,1H),5.07(dd,J＝14.8,6.9Hz,1H),4.34(q,J＝16.9Hz,2H),3.73(s,2H),3.61-3.44(m,2H),3.26-3.07(m,3H),3.04-2.84(m,4H),2.76(d,J＝15.5Hz,1H),2.52-2.37(m,1H),2.27(s,2H),2.14(s,3H),1.92(s,1H),1.85(s,1H),1.58(t,J＝6.0Hz,2H),1.02(s,6H).LCMS(ESI)C₃₃H₄₁FN₅O₃ ⁺[M+H]⁺： calculated 574.32, found 574.4) was prepared according to the procedure of scheme 1.

EXAMPLE 225 preparation of Compound GT-10287

The title compound GT-10287 (25 mg, white solid, yield 66％).¹H NMR(400MHz,MeOD)δ7.81(s,1H),7.62-7.50(m,5H),7.46-7.33(m,3H),6.99(s,1H),6.90(d,J＝8.0Hz,1H),5.08(dd,J＝14.8,6.9Hz,,1H),4.53-4.26(m,4H),3.95(s,1H),3.58(s,1H),3.45(d,J＝11.8Hz,1H),3.05(d,J＝11.6Hz,1H),2.99(brs,1H),2.92-2.81(m,1H),2.79-2.72(m,1H),2.48-2.41(m,1H),2.34(d,J＝11.7Hz,1H),2.20-1.97(m,2H),1.38(d,J＝11.9Hz,1H).LCMS(ESI)C₃₁H₃₁ClN₅O₃ ⁺[M+H]⁺： calculated 556.21, found 556.3) was prepared according to the procedure of scheme 1.

EXAMPLE 226 preparation of Compound GT-10288

The title compound GT-10288 (26 mg, white solid, yield 69％).¹H NMR(400MHz,MeOD)δ7.90(s,1H),7.79-7.75(m,1H),7.69(d,J＝8.3Hz,2H),7.60(t,J＝8.7Hz,2H),7.52(d,J＝8.3Hz,1H),7.47(d,J＝8.3Hz,2H),7.03(s,1H),6.94(d,J＝8.2Hz,1H),5.14-5.00(m,1H),4.67-4.64(m,1H),4.57(d,J＝13.0Hz,1H),4.47-4.24(m,4H),3.79-3.73(m,1H),3.65-3.54(m,1H),3.51-3.45(m,1H),3.12(brs,1H),2.96-2.82(m,1H),2.77-3.73(m,1H),2.55-2.30(m,3H),2.20-2.04(m,1H).LCMS(ESI)C₃₁H₃₁ClN₅O₃ ⁺[M+H]⁺： calculated 556.21, found 556.3) was prepared according to the procedure of scheme 1.

EXAMPLE 227 preparation of Compound GT-10289

The title compound GT-10289 (14 mg, white solid, yield 38％).¹H NMR(400MHz,MeOD)δ7.53(d,J＝8.3Hz,1H),7.31-7.10(m,4H),7.02(s,1H),6.93(d,J＝8.1Hz,1H),5.20-5.00(m,1H),4.34(q,J＝17.1Hz,2H),4.20(d,J＝20.3Hz,1H),3.94-3.67(m,2H),3.59(s,2H),3.56-3.43(m,1H),3.22-2.96(m,2H),2.96-2.82(m,1H),2.82-2.65(m,1H),2.57-2.25(m,5H),2.22-2.00(m,2H),1.81(brs,4H),1.28(d,J＝10.5Hz,1H).LCMS(ESI)C₃₁H₃₅FN₅O₃ ⁺[M+H]⁺： calculated 544.27, found 544.3) was prepared according to the procedure of scheme 1.

EXAMPLE 228 preparation of Compound GT-10290

The title compound GT-10290 (25 mg, white solid, yield 65％).¹H NMR(400MHz,MeOD)δ7.59-7.43(m,3H),7.35-7.22(m,2H),7.01(s,1H),6.92(d,J＝7.8Hz,1H),5.17-5.02(m,1H),4.36(s,3H),4.34-4.15(m,2H),3.93(s,2H),3.83(d,J＝13.8Hz,2H),3.76-3.45(m,3H),3.18-2.98(m,2H),2.96-2.71(m,3H),2.55-2.44(m,3H),2.41-2.27(m,1H),2.21-2.02(m,2H),1.30(d,J＝11.2Hz,1H).LCMS(ESI)C₃₀H₃₃ClN₅O₄ ⁺[M+H]⁺： calculated 562.22, found 562.3) was prepared according to the procedure of scheme 1.

EXAMPLE 229 preparation of Compound GT-10291

The title compound GT-10291 (18 mg, white solid, yield 48％).¹H NMR(400MHz,MeOD)δ7.53(d,J＝8.2Hz,1H),7.43-7.12(m,4H),7.01(s,1H),6.92(d,J＝7.1Hz,1H),5.16-5.02(m,1H),4.36(s,4H),4.25-4.20(m,1H),3.93(s,2H),3.84(d,J＝12.8Hz,1H),3.75-3.45(m,3H),3.21-2.98(m,2H),2.98-2.72(m,2H),2.62-2.25(m,4H),2.23-2.00(m,2H),1.28(d,J＝10.7Hz,1H).LCMS(ESI)C₃₀H₃₃FN₅O₄ ⁺[M+H]⁺： calculated 546.25, found 546.3) was prepared according to the procedure of scheme 1.

EXAMPLE 230 preparation of Compound GT-10292

The title compound GT-10292 (22 mg, white solid, yield 55％).¹H NMR(400MHz,MeOD)δ7.61-7.42(m,3H),7.36-7.20(m,2H),7.01(s,1H),6.92(d,J＝7.2Hz,1H),5.17-5.03(m,1H),4.37(s,4H),4.22-6.16(m,1H),4.01-3.76(m,2H),3.75-3.44(m,3H),3.14-2.98(m,2H),2.96-2.85(m,1H),2.82-2.69(m,1H),2.52-2.33(m,4H),2.22-1.99(m,2H),1.31(s,6H).LCMS(ESI)C₃₂H₃₇ClN₅O₄ ⁺[M+H]⁺： calculated 590.25, found 590.3) was prepared according to the procedure of scheme 1.

EXAMPLE 231 preparation of Compound GT-10293

The title compound GT-10293 (20 mg, white solid, yield 49％).¹H NMR(400MHz,MeOD)δ7.64-7.42(m,3H),7.29-7.21(m,2H),7.01(s,1H),6.93(d,J＝8.1Hz,1H),5.18-5.02(m,1H),4.49-4.32(m,2H),4.32-4.15(m,1H),3.99-3.73(m,2H),3.73-3.44(m,3H),3.20-2.95(m,2H),2.96-2.56(m,7H),2.56-2.35(m,1H),2.35-2.18(m,2H),2.18-2.01(m,2H).LCMS(ESI)C₃₁H₃₃ClF₂N₅O₃ ⁺[M+H]⁺： calculated 596.22, found 596.3) was prepared according to the procedure of scheme 1.

EXAMPLE 232 preparation of Compound GT-10294

The title compound GT-10294 (20 mg, white solid, yield 49％).¹H NMR(400MHz,MeOD)δ7.54-7.43(m,3H),7.25-7.18(m,2H),7.03(s,1H),6.93(d,J＝7.2Hz,1H),5.16-5.02(m,1H),4.49-4.31(m,2H),4.24-4.14(m,1H),3.95-3.69(m,2H),3.61-3.51(m,3H),3.28(s,3H),3.19-2.95(m,2H),2.93-2.74(m,3H),2.52-2.30(m,5H),2.23-1.96(m,3H),1.86-1.68(m,1H),1.33(s,3H).LCMS(ESI)C₃₃H₃₉ClN₅O₄ ⁺[M+H]⁺： calculated 604.27, found 604.3) was prepared according to the procedure of scheme 1.

EXAMPLE 233 preparation of Compound GT-10295

The title compound GT-10295 (16 mg, white solid, yield 41％).¹H NMR(400MHz,MeOD)δ7.53(d,J＝8.2Hz,1H),7.30-7.09(m,4H),7.01(s,1H),6.93(d,J＝8.0Hz,1H),5.16-5.01(m,1H),4.45-4.33(m,2H),4.16(d,J＝27.3Hz,1H),3.76(d,J＝13.8Hz,1H),3.63(d,J＝7.0Hz,1H),3.61-3.41(m,2H),3.13-3.01(m,2H),2.95-2.62(m,3H),2.56-2.34(m,2H),2.30(s,2H),2.25-2.00(m,4H),1.60(s,2H),1.04(s,6H).LCMS(ESI)C₃₃H₃₉FN₅O₃ ⁺[M+H]⁺： calculated 572.30, found 572.3) was prepared according to the procedure of scheme 1.

EXAMPLE 234 preparation of Compound GT-10330

The title compound GT-10330 (8 mg, white solid, 22% yield) was prepared according to the procedure of scheme 2 LCMS (ESI) C ₃₂H₃₄N₅O₃ ⁺[M+H]⁺:calculated 536.27, found 536.3.

EXAMPLE 235 preparation of Compound GT-10331

The title compound GT-10331 (10 mg, white solid, yield 28％).¹H NMR(400MHz,MeOD)δ7.74(d,J＝6.6Hz,3H),7.63-7.40(m,7H),7.28(s,1H),7.19(s,1H),7.08(d,J＝7.9Hz,1H),5.64(s,1H),5.08(dd,J＝13.3,4.8Hz,1H),4.47-4.31(m,2H),3.60(d,J＝11.5Hz,2H),3.51(s,2H),3.00-2.82(m,2H),2.77(d,J＝15.7Hz,1H),2.54-2.41(m,1H),2.33(brs,2H),2.25(brs,1H),2.19-2.00(m,3H).LCMS(ESI)C₃₂H₃₄N₅O₃ ⁺[M+H]⁺： calculated 536.27, found 536.3) was prepared according to the procedure of FIG. 2.

EXAMPLE 236 preparation of Compound GT-10332

The title compound GT-10332 (14 mg, white solid, yield 29％).¹H NMR(400MHz,MeOD)δ7.69(s,4H),7.62-7.38(m,8H),5.50(s,1H),5.05(dd,J＝12.7,5.4Hz,1H),3.54-3.38(m,2H),3.18(brs,4H),2.93-2.77(m,2H),2.74-2.63(m,3H),2.13-2.02(m,1H).LCMS(ESI)C₃₀H₂₉FN₅O₄ ⁺[M+H]⁺： calculated 542.22, found 542.3) was prepared according to the procedure of scheme 2.

EXAMPLE 237 preparation of Compound GT-10333

The title compound GT-10333 (12 mg, white solid, yield 25％).¹H NMR(400MHz,MeOD)δ7.68(s,4H),7.58-7.40(m,6H),7.09(s,1H),6.83(s,1H),5.48(s,1H),5.09-5.00(m,1H),3.43(dd,J＝20.6,15.5Hz,3H),3.27-3.14(m,2H),3.10-2.98(m,2H),2.86-2.69(m,4H),2.13-1.96(m,1H).LCMS(ESI)C₃₀H₂₉FN₅O₄ ⁺[M+H]⁺： calculated 542.22, found 542.3) was prepared according to the procedure of scheme 2.

EXAMPLE 238 preparation of Compound GT-10334

The title compound GT-10334 (25 mg, white solid, yield 66％).¹H NMR(400MHz,MeOD)δ7.84(s,1H),7.65-7.47(m,5H),7.45-7.35(m,3H),6.98(s,1H),6.90(d,J＝7.5Hz,1H),5.07(dd,J＝13.3,4.7Hz,1H),4.48(s,2H),4.34(q,J＝16.8Hz,2H),3.41(s,2H),3.21(d,J＝9.9Hz,2H),3.15-3.04(m,2H),2.94-2.83(m,1H),2.76(d,J＝17.2Hz,1H),2.44(dd,J＝13.1,4.3Hz,1H),2.28(brs,2H),2.16-2.10(m,1H),2.02-1.97(m,2H).LCMS(ESI)C₃₂H₃₃ClN₅O₃ ⁺[M+H]⁺： calculated 570.23, found 570.2) was prepared according to the procedure of scheme 1.

EXAMPLE 239 preparation of Compound GT-10335

The title compound GT-10335 (35 mg, white solid, yield 70％).¹H NMR(400MHz,MeOD)δ7.77(s,1H),7.61-7.52(m,4H),7.48(t,J＝7.8Hz,2H),7.41-7.36(m,3H),5.04(dd,J＝12.7,5.4Hz,1H),4.44(s,2H),3.48-3.37(m,2H),3.20-2.95(m,6H),2.82(dd,J＝17.8,4.3Hz,1H),2.77-2.63(m,2H),2.17-2.03(m,1H).LCMS(ESI)C₃₀H₂₈ClFN₅O₄ ⁺[M+H]⁺： calculated 576.18, found 576.2) was prepared according to the procedure of FIG. 3.

EXAMPLE 240 preparation of Compound GT-10336

The title compound GT-10336 (30 mg, white solid, yield 60％).¹H NMR(400MHz,MeOD)δ7.77(s,1H),7.64-7.50(m,4H),7.40-7.35(m,3H),7.03(s,1H),6.79(s,1H),5.03(dd,J＝12.6,5.2Hz,1H),4.44(s,2H),3.41-3.35(m,2H),3.08(s,4H),2.98-2.87(m,2H),2.82(dd,J＝18.3,4.8Hz,1H),2.77-2.62(m,2H),2.16-1.98(m,1H).LCMS(ESI)C₃₀H₂₈ClFN₅O₄ ⁺[M+H]⁺： calculated 576.18, found 576.2) was prepared according to the procedure of scheme 1.

Example 241 preparation of Compound GT-10337

The title compound GT-10337 (8 mg, white solid, yield 21％).¹H NMR(400MHz,MeOD)δ7.94(s,2H),7.66-7.49(m,3H),7.43-7.24(m,4H),7.02(s,1H),6.95(d,J＝5.1Hz,1H),5.97(s,1H),5.07(dd,J＝13.5,4.9Hz,1H),4.36(q,J＝16.6Hz,2H),4.09(brs,1H),3.21-3.18(m,4H),3.17-3.09(m,1H),2.94-2.83(m,2H),2.76(d,J＝15.0Hz,1H),2.61-2.39(m,4H),2.19-2.09(m,1H).LCMS(ESI)C₃₂H₃₂F₂N₅O₃ ⁺[M+H]⁺： calculated 572.25, found 572.3) was prepared according to the procedure of scheme 2.

EXAMPLE 242 preparation of Compound GT-10339

The title compound GT-10339 (8 mg, white solid, yield 21％).¹H NMR(400MHz,MeOD)δ7.77-7.43(m,7H),7.24(brs,2H),7.02(s,1H),6.96(d,J＝8.5Hz,1H),5.51(s,1H),5.07(dd,J＝13.6,5.2Hz,1H),4.46-4.29(m,2H),3.97(brs,1H),3.29-3.17(m,4H),3.14(brs,1H),2.92-2.79(m,2H),2.76(d,J＝18.7Hz,1H),2.64-2.35(m,4H),2.20-2.04(m,1H).LCMS(ESI)C₃₂H₃₂F₂N₅O₃ ⁺[M+H]⁺： calculated 572.25, found 572.3) was prepared according to the procedure of scheme 2.

EXAMPLE 243 preparation of Compound GT-10340

The title compound GT-10340 (10 mg, white solid, yield 25％).¹H NMR(400MHz,DMSO-d6)δ7.72(s,3H),7.65-7.37(m,6H),7.01(s,1H),6.95(d,J＝7.2Hz,1H),5.47(s,1H),5.07(dd,J＝13.5,4.8Hz,1H),4.36(q,J＝16.6Hz,2H),3.95(s,1H),3.23-3.05(m,3H),2.95-2.69(m,3H),2.57-2.29(m,4H),2.19-1.89(m,2H),1.30-1.24(m,1H).LCMS(ESI)C₃₂H₃₂Cl₂N₅O₃ ⁺[M+H]⁺： calculated 604.19, found 604.2) was prepared according to the procedure of FIG. 2.

EXAMPLE 244 preparation of Compound GT-10430

The title compound GT-10430 (25 mg, white solid, yield 70％).¹H NMR(400MHz,DMSO-d6)δ8.79(s,1H),7.88-7.81(m,1H),7.72(s,2H),7.56(d,J＝8.2Hz,1H),7.52-7.45(m,4H),7.18(s,1H),7.03(s,1H),6.97(d,J＝7.9Hz,1H),5.68(s,1H),5.07(dd,J＝13.3,5.0Hz,1H),4.36(q,J＝17.2Hz,2H),3.99(brs,1H),3.67(brs,1H),3.27-3.02(m,3H),2.94-2.85(m,2H),2.46(brs,5H),2.35-2.27(m,1H),2.21-2.03(m,1H).LCMS(ESI)C₃₁H₃₃N₆O₃ ⁺[M+H]⁺： calculated 537.26, found 537.3) was prepared according to the procedure of scheme 2.

EXAMPLE 245 preparation of Compound GT-10431

The title compound GT-10431 (12 mg, white solid, yield 34％).¹H NMR(400MHz,DMSO-d6)δ9.58(s,1H),9.32(d,J＝7.6Hz,1H),8.91(d,J＝5.3Hz,1H),8.24-8.13(m,1H),8.06(s,2H),7.57-7.49(m,4H),7.01(s,1H),6.95(d,J＝7.8Hz,1H),5.83(s,1H),5.07(dd,J＝13.0,4.9Hz,1H),4.46-4.27(m,2H),4.06(brs,1H),3.94(brs,1H),3.72(brs,1H),3.60(brs,1H),3.14-3.00(m,2H),2.97-2.82(m,1H),2.76(d,J＝17.7Hz,1H),2.68-2.65(m,1H),2.51-2.42(m,4H),2.22-2.05(m,1H).LCMS(ESI)C₃₁H₃₃N₆O₃ ⁺[M+H]⁺： calculated 537.26, found 537.3) was prepared according to the procedure of FIG. 2.

EXAMPLE 246 preparation of Compound GT-10459

The title compound GT-10459 (8 mg, white solid, yield 22％).¹H NMR(400MHz,DMSO-d6)δ7.91-7.83(m,1H),7.79-7.70(m,2H),7.70-7.62(m,2H),7.60-7.41(m,8H),5.82(s,1H),5.15-5.02(m,1H),4.46-4.29(m,2H),4.21-4.13(m,1H),3.85-2.79(m,1H),3.73-3.49(m,3H),3.23-3.15(m,1H),3.08-2.98(m,1H),2.92-2.85(m,1H),2.82-2.71(m,1H),2.54-2.31(m,2H),2.21-2.06(m,1H).LCMS(ESI)C₃₁H₃₂N₅O₃ ⁺[M+H]⁺： calculated 522.25, found 522.3) was prepared according to the procedure of FIG. 2.

EXAMPLE 247 preparation of Compound GT-10460

The title compound GT-10460 (8 mg, white solid, yield 21%) was prepared according to the method of scheme 2 LCMS (ESI) C ₃₁H₃₀F₂N₅O₃ ⁺[M+H]⁺:calculated 558.23, found 558.3.

EXAMPLE 248 preparation of Compound GT-10461

The title compound GT-10461 (14 mg, white solid, yield 36％).¹H NMR(400MHz,DMSO-d6)δ7.70-7.38(m,7H),7.30-7.15(m,2H),7.05(s,1H),6.97(s,1H),5.61(s,1H),5.17-5.02(m,1H),4.50-4.31(m,2H),4.28-4.14(m,1H),3.92-3.80(m,2H),3.69-3.52(m,1H),3.21-3.07(m,1H),2.91-2.85(m,2H),2.65-2.41(m,3H),2.22-2.05(m,1H),1.37-1.24(m,1H).LCMS(ESI)C₃₁H₃₀F₂N₅O₃ ⁺[M+H]⁺： calculated 558.23, found 558.3) was prepared according to the procedure of FIG. 2.

Example 249 preparation of Compound GT-10462

The title compound GT-10462 (8 mg, white solid, yield 21％).¹H NMR(400MHz,DMSO-d6)δ7.87-7.68(m,3H),7.59-7.52(m,1H),7.41-7.31(m,1H),7.31-7.17(m,4H),7.10-6.95(m,2H),5.16-5.03(m,1H),4.47-4.37(m,2H),4.17(d,J＝23.0Hz,1H),3.84-3.77(m,2H),3.63-3.54(m,1H),3.21-3.14(m,2H),2.98-2.82(m,1H),2.76(d,J＝17.0Hz,1H),2.45-2.36(m,2H),2.21-2.06(m,1H),1.32-1.29(m,1H),1.27-1.23(m,1H).LCMS(ESI)C₃₁H₃₀F₂N₅O₃ ⁺[M+H]⁺： calculated 558.23, found 558.3) was prepared according to the procedure of scheme 2.

EXAMPLE 250 preparation of Compound GT-10463

The title compound GT-10463 (12 mg, white solid, yield 30％).¹H NMR(400MHz,DMSO-d6)δ7.88-7.62(m,4H),7.60-7.42(m,5H),7.37-7.28(m,1H),7.02-6.89(m,1H),5.16-5.00(m,1H),4.52-4.29(m,2H),4.27-4.11(m,1H),3.92-3.69(m,2H),3.64-3.59(m,1H),3.25-3.06(m,1H),2.98-2.70(m,3H),2.67-2.51(m,1H),2.44-2.33(m,2H),2.23-2.05(m,1H),1.38-1.20(m,1H).LCMS(ESI)C₃₁H₃₀Cl₂N₅O₃ ⁺[M+H]⁺： calculated 590.17, found 590.2) was prepared according to the procedure of FIG. 2.

Example 251 preparation of Compound GT-10464

The title compound GT-10464 (20 mg, white solid, yield 56％).¹H NMR(400MHz,DMSO-d6)δ8.77(d,J＝16.8Hz,1H),8.00-7.86(m,1H),7.68(dd,J＝20.1,4.4Hz,2H),7.62-7.52(m,2H),7.54-7.37(m,4H),7.21-7.12(m,1H),7.02(t,J＝9.1Hz,1H),5.83(s,1H),5.07(d,J＝11.9Hz,1H),4.49-4.28(m,2H),4.02-3.81(m,3H),3.43-4.39(m,1H),3.18(d,J＝12.8Hz,1H),3.12(brs,1H),2.98-2.82(m,1H),2.76(d,J＝16.2Hz,1H),2.55-2.39(m,3H),2.14(brs,1H).LCMS(ESI)C₃₀H₃₁N₆O₃ ⁺[M+H]⁺： calculated 523.25, found 523.3) was prepared according to the procedure of scheme 2.

Example 252 preparation of Compound GT-10465

The title compound GT-10465 (30 mg, white solid, yield 65％).¹H NMR(400MHz,DMSO-d6)δ9.92(s,1H),9.32-9.08(m,2H),9.00(s,2H),8.69-8.53(m,1H),8.32-8.25(m,1H),8.17-8.11(m,1H),7.99-7.95(m,1H),7.84(s,1H),7.65-7.53(m,4H),7.50-7.42(m,5H),7.27-6.93(m,2H),6.21(s,1H),5.16-5.04(m,1H),4.50-4.30(m,2H),4.31-4.01(m,2H),4.03-3.69(m,2H),3.42-3.38(m,2H),3.22-3.12(m,1H),2.97-2.83(m,1H),2.78-2.74(m,1H),2.58(s,1H),2.48-2.36(m,2H),2.18-2.06(m,1H).LCMS(ESI)C₄₂H₄₀N₇O₃ ⁺[M+H]⁺： calculated 690.32, found 690.3) was prepared according to the procedure of scheme 2.

EXAMPLE 253 preparation of Compound GT-10475

The title compound GT-10475 (6 mg, white solid, yield 17％).¹H NMR(400MHz,MeOD)δ9.50(s,1H),9.26(d,J＝8.2Hz,1H),8.93(d,J＝5.6Hz,1H),8.27-8.14(m,1H),7.94(d,J＝7.3Hz,2H),7.63(d,J＝8.2Hz,1H),7.58-7.45(m,3H),7.33(s,1H),7.12(s,1H),6.25(s,1H),5.10(dd,J＝13.3,4.9Hz,2H),4.60-4.35(m,2H),3.66(s,4H),3.39(s,4H),3.02-2.84(m,2H),2.77(d,J＝15.8Hz,1H),2.61-2.39(m,1H),2.25-2.00(m,1H).LCMS(ESI)C₃₁H₃₃N₆O₃ ⁺[M+H]⁺： calculated 537.26 found 537.3) was prepared according to the procedure of scheme 2.

EXAMPLE 254 preparation of Compound GT-10476

The title compound GT-10476 (12 mg, white solid, yield 26％).¹H NMR(400MHz,MeOD)δ9.88(s,1H),9.24(d,J＝28.3Hz,1H),9.16-8.90(m,3H),8.83-8.70(m,1H),8.27(d,J＝21.9Hz,2H),8.11-8.02(m,1H),7.84(s,2H),7.64(s,1H),7.56-7.40(m,8H),7.13(s,1H),6.39(s,1H),5.11(d,J＝10.6Hz,1H),4.58-4.36(m,2H),3.87-3.58(m,2H),3.53-3.38(m,4H),3.30-3.08(m,5H),2.95-2.84(m,1H),2.77(d,J＝16.0Hz,1H),2.53-2.34(m,1H),2.16(brs,1H).LCMS(ESI)C₄₃H₄₂N₇O₃ ⁺[M+H]⁺： calculated 704.33 found 704.4) was prepared according to the procedure of FIG. 2.

EXAMPLE 255 preparation of Compound GT-10477

The title compound GT-10477 (5 mg, white solid, yield 14%) was prepared according to the procedure of scheme 2 LCMS (ESI) C ₃₁H₃₃N₆O₃ ⁺[M+H]⁺:calculated 537.26 found 537.3.

EXAMPLE 256 preparation of Compound GT-10478

The title compound GT-10478 (16 mg, white solid, yield 45％).¹H NMR(400MHz,MeOD)δ8.90-8.62(m,1H),7.94-7.76(m,1H),7.55(brs,3H),7.45(s,4H),7.35(s,1H),7.00(s,1H),6.91(s,1H),5.90(d,J＝6.7Hz,1H),5.12-5.06(m,1H),4.60(s,1H),4.34(brs,2H),3.70(s,1H),3.55-3.48(m,1H),3.21-2.70(m,5H),2.47(brs,2H),2.14(brs,2H).LCMS(ESI)C₃₀H₃₁N₆O₃ ⁺[M+H]⁺： calculated 523.25 found 523.3) was prepared according to the procedure of scheme 2.

EXAMPLE 257 preparation of Compound GT-10479

The title compound GT-10479 (4 mg, white solid, yield 11%) was prepared according to the procedure of scheme 2 LCMS (ESI) C ₃₀H₃₁N₆O₃ ⁺[M+H]⁺: 523.25 calculated, 523.3 measured.

EXAMPLE 258 preparation of Compound GT-10480

The title compound GT-10480 (10 mg, white solid, yield 22％).¹H NMR(400MHz,DMSO-d6)δ9.19-9.02(m,1H),9.00-8.85(m,2H),8.77(dd,J＝27.0,4.9Hz,1H),8.45-8.30(m,1H),8.29-8.16(m,1H),7.99-7.95(m,1H),7.91-7.79(m,1H),7.77-7.63(m,2H),7.60-7.38(m,10H),6.96-6.81(m,1H),6.07(s,1H),5.15-5.10(m,1H),4.66(brs,1H),4.42-4.19(m,2H),3.62(s,1H),3.44-3.33(m,3H),3.11-2.84(m,3H),2.81-2.74(m,1H),2.50-2.32(m,2H),2.25-1.98(m,2H).LCMS(ESI)C₄₂H₄₀N₇O₃ ⁺[M+H]⁺： calculated 690.32, found 690.4) was prepared according to the procedure of FIG. 2.

EXAMPLE 259 preparation of Compound GT-10518

The title compound GT-10518 (14 mg, white solid, yield 39％).¹H NMR(400MHz,MeOD)δ8.73(d,J＝4.4Hz,2H),7.94(t,J＝7.1Hz,2H),7.74(d,J＝7.8Hz,2H),7.57(d,J＝8.3Hz,1H),7.49(dd,J＝7.0,5.2Hz,2H),7.04(s,1H),6.97(d,J＝8.0Hz,1H),6.08(s,1H),5.07(dd,J＝13.3,4.9Hz,2H),4.37(q,J＝16.8Hz,2H),3.89(s,2H),3.43-3.35(m,2H),3.13(d,J＝11.0Hz,2H),2.96-2.82(m,1H),2.76(d,J＝17.5Hz,1H),2.51-2.43(m,4H),2.22-2.04(m,1H).LCMS(ESI)C₃₀H₃₂N₇O₃ ⁺[M+H]⁺： calculated 538.26, found 538.3) was prepared according to the procedure of scheme 2.

EXAMPLE 260 preparation of Compound GT-10519

The title compound GT-10519 (10 mg, white solid, yield 22％).¹H NMR(400MHz,MeOD)δ8.67(s,2H),7.88(s,2H),7.63-7.49(m,3H),7.45(s,2H),7.00(br,s),6.92(s,1H),6.06(s,1H),5.11-5.05(m,2H),4.60(s,1H),4.41-4.26(m,2H),3.74(s,1H),3.05(s,2H),2.88(s,2H),2.79-2.75(m,1H),2.52-2.46(m,2H),2.24(brs,1H),2.14(brs,1H).LCMS(ESI)C₄₂H₄₀N₇O₃ ⁺[M+H]⁺： calculated 690.32, found 690.4) was prepared according to the procedure of scheme 2.

EXAMPLE 261 preparation of Compound GT-10520

The title compound GT-10520 (10 mg, white solid, yield 22％).¹H NMR(400MHz,MeOD)δ8.74(s,2H),8.08(t,J＝7.0Hz,2H),7.87(dd,J＝23.9,7.8Hz,2H),7.65-7.55(m,3H),7.22(s,1H),7.09(d,J＝7.6Hz,1H),6.13(s,1H),5.23-5.05(m,4H),4.45-4.34(m,2H),4.05(d,J＝12.7Hz,2H),3.61(s,1H),2.99-2.83(m,1H),2.76(d,J＝16.8Hz,1H),2.52-2.42(m,3H),2.15(brs,1H).LCMS(ESI)C₄₂H₄₀N₇O₃ ⁺[M+H]⁺： calculated 690.32, found 690.4) was prepared according to the procedure of scheme 2.

EXAMPLE 262 preparation of Compound GT-10521

The title compound GT-10521 (10 mg, white solid, yield 22％).¹H NMR(400MHz,MeOD)δ9.18(s,1H),8.85-8.70(m,2H),7.93(s,1H),7.84-7.71(m,2H),7.59-7.46(m,4H),7.11(s,1H),7.01(s,1H),5.11-5.03(m,1H),4.45-4.31(m,2H),3.98-3.83(m,2H),3.25-3.21(m,4H),2.95-2.83(m,1H),2.80-2.74(m,1H),2.57-2.34(m,3H),2.19-2.11(m,1H).LCMS(ESI)C₄₂H₄₀N₇O₃ ⁺[M+H]⁺： calculated 690.32, found 690.4) was prepared according to the procedure of scheme 2.

EXAMPLE 263 preparation of Compound GT-10545

The title compound GT-10545 (10 mg, white solid, yield 22％).¹H NMR(400MHz,MeOD)δ7.97-7.83(m,1H),7.55(d,J＝8.2Hz,1H),7.52-7.45(m,2H),7.40-7.33(m,2H),7.29-7.24(m,2H),7.07(s,1H),6.94(d,J＝8.4Hz,1H),5.07(dd,J＝13.2,4.9Hz,1H),4.51-4.31(m,2H),3.76-3.70(m,1H),3.59(brs,3H),3.40-3.35(m,2H),3.11(s,2H),2.95-2.82(m,1H),2.76(d,J＝15.4Hz,1H),2.55-2.41(m,1H),2.22(s,2H),2.18-2.07(m,1H).LCMS(ESI)C₄₂H₄₀N₇O₃ ⁺[M+H]⁺： calculated 690.32, found 690.4) was prepared according to the procedure of scheme 2.

EXAMPLE 264 preparation of Compound GT-10546

The title compound GT-10546 (10 mg, white solid, yield 22％).¹H NMR(400MHz,MeOD)δ7.63-7.48(m,6H),7.27-7.13(m,3H),7.02(s,1H),6.93(dd,J＝9.9,4.7Hz,1H),5.75(s,1H),5.13-5.02(m,1H),4.51-4.39(m,1H),4.35(d,J＝6.9Hz,1H),3.62-3.44(m,3H),3.45-3.35(m,3H),3.18-2.98(m,2H),2.97-2.82(m,1H),2.80-2.74(m,1H),2.54-2.38(m,1H),2.28-2.06(m,3H).LCMS(ESI)C₄₂H₄₀N₇O₃ ⁺[M+H]⁺： calculated 690.32, found 690.4) was prepared according to the procedure of scheme 2.

EXAMPLE 265 preparation of Compound GT-10547

The title compound GT-10547 (10 mg, white solid, yield 22％).¹H NMR(400MHz,MeOD)δ7.98-7.84(m,1H),7.82-7.66(m,2H),7.54(d,J＝9.6Hz,1H),7.39-7.33(m,1H),7.31-7.16(m,3H),7.12-6.98(m,2H),6.97-6.88(m,1H),5.72(s,1H),4.43-4.27(m,1H),3.70-3.55(m,2H),3.55-3.46(m,4H),3.26-3.15(m,1H),3.15-2.97(m,1H),2.98-2.83(m,1H),2.83-2.71(m,1H),2.52-2.36(m,1H),2.30-2.05(m,2H),1.37-1.25(m,3H).LCMS(ESI)C₄₂H₄₀N₇O₃ ⁺[M+H]⁺： calculated 690.32, found 690.4) was prepared according to the procedure of FIG. 2.

EXAMPLE 266 preparation of Compound GT-10548

The title compound GT-10548 (10 mg, white solid, yield 22％).¹H NMR(400MHz,D MeOD)δ7.69(d,J＝4.6Hz,4H),7.52(brs,5H),7.01(s,1H),6.98-6.88(m,1H),5.72(s,1H),5.08(dd,J＝13.6,7.9Hz,1H),4.47-4.29(m,2H),3.66-3.60(m,1H),3.58-3.40(m,4H),3.15-3.03(m,2H),2.99-2.70(m,3H),2.55-2.37(m,1H),2.25-2.15(m,3H).LCMS(ESI)C₄₂H₄₀N₇O₃ ⁺[M+H]⁺： calculated 690.32, found 690.4) was prepared according to the procedure of scheme 2.

EXAMPLE 267 preparation of Compound GT-10563

The title compound GT-10563 (10 mg, white solid, yield 22％).¹H NMR(400MHz,MeOD)δ7.75-7.58(m,2H),7.54-7.44(m,3H),7.38-7.27(m,4H),7.07-6.99(m,1H),6.94-6.76(m,1H),5.21-5.00(m,1H),4.49-4.22(m,2H),3.77-3.71(m,1H),3.26-3.17(m,3H),3.09-2.97(m,2H),2.96-2.84(m,2H),2.79-2.74(m,1H),2.48-2.41(m,2H),2.25-2.01(m,2H).LCMS(ESI)C₄₂H₄₀N₇O₃ ⁺[M+H]⁺： calculated 690.32, found 690.4) was prepared according to the procedure of FIG. 2.

EXAMPLE 268 preparation of Compound GT-10564

The title compound GT-10564 (10 mg, white solid, yield 22％).¹H NMR(400MHz,MeOD)δ7.67-7.47(m,3H),7.44-7.28(m,3H),7.26-7.14(m,2H),7.12-6.74(m,3H),5.19-5.02(m,1H),4.53-4.16(m,3H),3.82-3.50(m,2H),3.41-3.38(m,2H),3.15-3.12(m,1H),2.98-2.64(m,3H),2.54-3.44(m,2H),2.27-1.89(m,2H).LCMS(ESI)C₄₂H₄₀N₇O₃ ⁺[M+H]⁺： calculated 690.32, found 690.4) was prepared according to the procedure of scheme 2.

EXAMPLE 269 preparation of Compound GT-10565

The title compound GT-10565 (10 mg, white solid, yield 22％).¹H NMR(400MHz,MeOD)δ7.70-7.62(m,1H),7.56-7.48(m,2H),7.39-7.30(m,2H),7.28-7.24(m,2H),7.21-7.10(m,2H),7.07-7.01(m,2H),5.08(dd,J＝13.7,5.6Hz,1H),4.58-4.53(m,1H),4.37(d,J＝6.9Hz,1H),4.34-4.23(m,2H),3.65-3.52(m,3H),2.97-2.81(m,2H),2.80-2.72(m,2H),2.52-2.30(m,2H),2.16-2.09(m,2H).LCMS(ESI)C₄₂H₄₀N₇O₃ ⁺[M+H]⁺： calculated 690.32, found 690.4) was prepared according to the procedure of FIG. 2.

EXAMPLE 270 preparation of Compound GT-10566

The title compound GT-10566 (10 mg, white solid, yield 22％).¹H NMR(400MHz,MeOD)δ7.67-7.61(m,2H),7.56-7.44(m,8H),6.99-6.94(m,1H),5.18-5.04(m,1H),4.46-4.15(m,4H),3.74-3.64(m,3H),2.88-2.81(m,2H),2.82-2.71(m,2H),2.55-2.30(m,2H),2.22-2.04(m,2H).LCMS(ESI)C₄₂H₄₀N₇O₃ ⁺[M+H]⁺： calculated 690.32, found 690.4) was prepared according to the procedure of scheme 2.

EXAMPLE 271 preparation of Compound GT-10568

The title compound GT-10568 (10 mg, white solid, yield 22％).¹H NMR(400MHz,MeOD)δ7.67(d,J＝6.3Hz,4H),7.61-7.31(m,7H),7.01(s,1H),6.93(d,J＝5.4Hz,1H),5.67(s,1H),5.07(dd,J＝13.0,5.1Hz,1H),4.46-4.26(m,2H),3.60-3.42(m,4H),3.25-3.22(m,2H),3.12-3.03(m,2H),2.92-2.85(m,1H),2.76(d,J＝15.6Hz,1H),2.54-2.43(m,1H),2.33-2.17(m,1H),2.17-2.01(m,2H).LCMS(ESI)C₄₂H₄₀N₇O₃ ⁺[M+H]⁺： calculated 690.32, found 690.4) was prepared according to the procedure of scheme 2.

EXAMPLE 272 preparation of Compound GT-10569

The title compound GT-10569 (10 mg, white solid, yield 22％).¹H NMR(400MHz,MeOD)δ8.77(d,J＝3.2Hz,1H),7.90(td,J＝7.8,1.6Hz,1H),7.70-7.61(m,2H),7.57(d,J＝8.4Hz,1H),7.51(d,J＝8.1Hz,1H),7.49-7.42(m,4H),7.11(s,1H),6.99(d,J＝8.4Hz,1H),5.90(s,1H),5.07(dd,J＝13.2,5.1Hz,1H),4.37(q,J＝17.2Hz,2H),3.55-3.50(m,1H),3.47-3.33(m,5H),3.17(s,2H),2.86(dd,J＝13.3,5.0Hz,1H),2.76(d,J＝15.5Hz,1H),2.45(dd,J＝13.1,4.5Hz,1H),2.18-2.11(m,3H).LCMS(ESI)C₄₂H₄₀N₇O₃ ⁺[M+H]⁺： calculated 690.32, found 690.4) was prepared according to the procedure of scheme 2.

Example 273 preparation of Compound GT-10645

The title compound GT-10645 (10 mg, white solid, yield 22％).¹H NMR(400MHz,MeOD)δ9.48(s,1H),9.22(d,J＝8.2Hz,1H),8.90(d,J＝5.5Hz,1H),8.18(dd,J＝8.1,5.9Hz,1H),7.91(d,J＝7.5Hz,2H),7.54(dd,J＝14.4,8.0Hz,3H),7.48(d,J＝7.2Hz,1H),7.09(s,1H),6.97(d,J＝8.3Hz,1H),6.14(s,1H),5.08(dd,J＝13.3,5.1Hz,1H),4.37(q,J＝16.9Hz,2H),3.54(s,4H),3.47-3.35(m,2H),3.23-3.08(m,2H),2.91-2.82(m,1H),2.77(d,J＝15.7Hz,1H),2.45(qd,J＝13.4,4.8Hz,1H),2.27(brs,2H),2.19-2.06(m,1H).LCMS(ESI)C₄₂H₄₀N₇O₃ ⁺[M+H]⁺： calculated 690.32, found 690.4) was prepared according to the procedure of scheme 2.

EXAMPLE 274 preparation of Compound GT-10646

The title compound GT-10646 (10 mg, white solid, yield 22％).¹H NMR(400MHz,MeOD)δ10.00(d,J＝14.2Hz,1H),9.31-9.10(m,2H),9.09-8.94(m,2H),8.81-8.63(m,1H),8.35-8.18(m,2H),7.98(d,J＝8.8Hz,1H),7.83(t,J＝5.3Hz,2H),7.56(dd,J＝7.7,3.3Hz,3H),7.54-7.43(m,6H),7.12(s,1H),6.97(d,J＝7.8Hz,1H),6.29(d,J＝8.9Hz,1H),5.08(dd,J＝13.3,5.1Hz,1H),4.50-4.26(m,2H),3.49(s,4H),3.36(s,2H),3.24-3.03(m,2H),2.87(dd,J＝13.2,5.1Hz,1H),2.82-2.71(m,1H),2.51-2.40(m,1H),2.24(brs,2H),2.18-2.07(m,1H).LCMS(ESI)C₄₂H₄₀N₇O₃ ⁺[M+H]⁺： calculated 690.32, found 690.4) was prepared according to the procedure of scheme 2.

EXAMPLE 275 preparation of Compound GT-10647

The title compound GT-10647 (10 mg, white solid, yield 22％).¹H NMR(400MHz,MeOD)δ8.71(d,J＝4.7Hz,2H),7.92(td,J＝7.8,1.7Hz,2H),7.64(d,J＝7.8Hz,2H),7.58(d,J＝8.4Hz,1H),7.47(dd,J＝7.2,5.3Hz,2H),7.09(s,1H),6.98(dd,J＝8.4,1.6Hz,1H),6.08(s,1H),5.07(dd,J＝13.3,5.1Hz,1H),4.84-4.77(m,2H),4.38(q,J＝16.8Hz,2H),3.60-3.46(m,4H),3.14(s,2H),2.91-2.84(m,1H),2.83-2.71(m,1H),2.46(qd,J＝13.1,4.7Hz,1H),2.22-2.09(m,3H).LCMS(ESI)C₄₂H₄₀N₇O₃ ⁺[M+H]⁺： calculated 690.32, found 690.4) was prepared according to the procedure of scheme 2.

EXAMPLE 276 preparation of Compound GT-10648

The title compound GT-10648 (10 mg, white solid, yield 22％).¹H NMR(400MHz,MeOD)δ7.87-7.85(m,1H),7.64-7.60(m,3H),7.54-7.41(m,8H),6.98-6.96(m,1H),5.09(dd,J＝13.3,5.0Hz,1H),4.78-4.70(m,2H),4.48-4.25(m,4H),3.76(d,J＝12.3Hz,1H),3.62-3.51(m,1H),3.28-3.23(m,2H),2.92-2.82(m,1H),2.82-2.74(m,2H),2.50-2.38(m,1H),2.19-2.07(m,1H).LCMS(ESI)C₄₂H₄₀N₇O₃ ⁺[M+H]⁺： calculated 690.32, found 690.4) was prepared according to the procedure of scheme 2.

EXAMPLE 277 preparation of Compound GT-10649

The title compound GT-10649 (10 mg, white solid, yield 22％).¹H NMR(400MHz,MeOD)δ7.90-7.82(m,1H),7.69-7.64(m,4H),7.55-7.48(m,5H),7.43(d,J＝8.4Hz,1H),7.05(s,1H),7.03(d,J＝8.4Hz,1H),5.10(dd,J＝13.3,5.0Hz,1H),4.80-4.72(m,2H),4.47-4.33(m,2H),3.68-3.64(m,2H),3.11-3.00(m,5H),2.89(dd,J＝13.2,5.2Hz,1H),2.78(dd,J＝19.0,3.1Hz,1H),2.67-2.63(m,2H),2.50-2.42(m,1H),2.21-2.10(m,1H).LCMS(ESI)C₄₂H₄₀N₇O₃ ⁺[M+H]⁺： calculated 690.32, found 690.4) was prepared according to the procedure of scheme 2.

EXAMPLE 278 preparation of Compound GT-10650

The title compound GT-10650 (10 mg, white solid, yield 22％).¹H NMR(400MHz,MeOD)δ7.74(t,J＝7.4Hz,2H),7.58(d,J＝8.4Hz,1H),7.55-7.51(m,2H),7.36(t,J＝7.6Hz,2H),7.34-7.27(m,2H),7.08(s,1H),7.01(d,J＝7.7Hz,1H),5.10(dd,J＝13.3,5.2Hz,1H),4.45-4.33(m,2H),3.91-3.76(m,2H),3.28-3.17(m,3H),3.16-3.05(m,4H),2.93-2.84(m,1H),2.81-2.75(m,1H),2.70-2.64(m,2H),2.46(dd,J＝13.1,4.7Hz,1H),2.22-2.10(m,1H).LCMS(ESI)C₄₂H₄₀N₇O₃ ⁺[M+H]⁺： calculated 690.32, found 690.4) was prepared according to the procedure of scheme 2.

Example 279 preparation of Compound GT-10651

The title compound GT-10651 (10 mg, white solid, yield 22％).¹H NMR(400MHz,MeOD)δ7.61-7.52(m,5H),7.50(d,J＝1.9Hz,1H),7.47(d,J＝1.8Hz,1H),7.26-7.19(m,2H),7.06(s,1H),7.03(d,J＝8.8Hz,1H),5.82(s,1H),5.10(dd,J＝13.2,5.2Hz,1H),4.48-4.33(m,2H),3.72(s,2H),3.20-3.02(m,6H),2.93-2.85(m,1H),2.77(dd,J＝17.9,4.8Hz,1H),2.72-2.56(m,2H),2.46(dd,J＝13.0,4.6Hz,1H),2.20-2.14(m,1H).LCMS(ESI)C₄₂H₄₀N₇O₃ ⁺[M+H]⁺： calculated 690.32, found 690.4) was prepared according to the procedure of scheme 2.

EXAMPLE 280 preparation of Compound GT-10652

The title compound GT-10652 (10 mg, white solid, yield 22％).¹H NMR(400MHz,MeOD)δ7.90(dd,J＝8.7,5.1Hz,1H),7.79-7.70(m,4H),7.28-7.24(m,4H),7.08(s,1H),7.06-7.00(m,2H),5.80(s,1H),5.10(dd,J＝13.3,5.1Hz,1H),4.46-4.33(m,2H),3.65(s,2H),3.11-3.03(m,6H),2.89(dd,J＝13.4,5.4Hz,1H),2.83-2.73(m,1H),2.73-2.56(m,2H),2.50-2.41(m,1H),2.23-2.09(m,1H).LCMS(ESI)C₄₂H₄₀N₇O₃ ⁺[M+H]⁺： calculated 690.32, found 690.4) was prepared according to the procedure of scheme 2.

EXAMPLE 281 preparation of Compound GT-10653

The title compound GT-10653 (10 mg, white solid, yield 22％).¹H NMR(400MHz,MeOD)δ8.79(d,J＝4.4Hz,1H),7.95(t,J＝7.5Hz,1H),7.68-7.65(m,3H),7.59-7.50(m,2H),7.48-7.43(m,3H),7.34(s,1H),7.22-7.18(m,1H),5.85(s,1H),5.11(dd,J＝13.3,5.1Hz,1H),4.45(q,J＝17.2Hz,2H),3.69(s,1H),3.58-3.46(m,2H),3.41(s,1H),3.30-3.02(m,6H),2.92-2.84(m,1H),2.81-2.72(m,1H),2.53-2.42(m,1H),2.19-2.13(m,1H).LCMS(ESI)C₄₂H₄₀N₇O₃ ⁺[M+H]⁺： calculated 690.32, found 690.4) was prepared according to the procedure of scheme 2.

EXAMPLE 282 preparation of Compound GT-10654

The title compound GT-10654 (10 mg, white solid, 22% yield) was prepared according to the procedure of scheme 2 LCMS (ESI) C ₄₂H₄₀N₇O₃ ⁺[M+H]⁺:calculated 690.32, found 690.4.

Example 283 preparation of Compound GT-10655

The title compound GT-10655 (10 mg, white solid, yield 22％).¹H NMR(400MHz,MeOD)δ8.77-8.70(m,2H),8.03(t,J＝7.6Hz,2H),7.80(d,J＝8.0Hz,2H),7.66(d,J＝8.4Hz,1H),7.60-7.51(m,2H),7.33(s,1H),7.19(d,J＝8.5Hz,1H),6.00(s,1H),5.11(dd,J＝13.3,5.1Hz,1H),4.43(q,J＝16.9Hz,2H),3.61-3.46(m,2H),3.40(d,J＝7.4Hz,2H),3.30-3.25(m,2H),3.15(s,4H),2.93-2.84(m,1H),2.83-2.69(m,1H),2.53-2.42(m,1H),2.22-2.07(m,1H).LCMS(ESI)C₄₂H₄₀N₇O₃ ⁺[M+H]⁺： calculated 690.32, found 690.4) was prepared according to the procedure of scheme 2.

EXAMPLE 284 preparation of Compound GT-09960

The title compound GT-09960 (white solid, 28mg, yield 42％).¹H NMR(400MHz,DMSO-d6)δ12.16(s,1H),10.95(s,1H),8.08-7.41(m,6H),7.41-7.07(m,5H),5.74(s,1H),5.04(dd,J＝13.2,5.0Hz,1H),4.24(dd,J＝49.9,16.9Hz,2H),3.38-3.18(m,5H),3.14-2.72(m,4H),2.59(d,J＝16.8Hz,1H),2.39-2.28(m,1H),2.04-1.86(m,1H).LCMS(ESI)C₃₀H₂₉F₃N₅O₃ ⁺[M+H]⁺： calculated 564.22, found 564.3) was prepared according to the procedure of scheme 2.

EXAMPLE 285 preparation of Compound GT-09961

The title compound GT-09961 (white solid, 15mg, yield 23％).¹H NMR(400MHz,DMSO-d6)δ12.34(s,1H),11.00(s,1H),8.05-7.44(m,5H),7.44-6.93(m,7H),5.74(s,1H),5.09(dd,J＝13.2,5.1Hz,1H),4.28(dd,J＝46.5,17.5Hz,2H),3.27(s,5H),3.08(s,2H),2.99-2.71(m,2H),2.63(d,J＝17.2Hz,1H),2.41-2.30(m,1H),2.09-1.98(m,1H).LCMS(ESI)C₃₀H₃₀F₂N₅O₃ ⁺[M+H]⁺： calculated 546.23, found 546.3) was prepared according to the procedure of scheme 2.

EXAMPLE 286 preparation of Compound GT-09962

The title compound GT-09962 (white solid, 9mg, yield 13％).¹H NMR(400MHz,DMSO-d6)δ12.02(s,1H),11.00(s,1H),7.94(d,J＝7.3Hz,3H),7.46(t,J＝7.4Hz,4H),7.41-7.33(m,2H),7.32-7.22(m,2H),7.11(d,1H),7.05(d,J＝7.3Hz,1H),5.63(d,J＝9.1Hz,1H),5.09(dd,J＝13.2,5.0Hz,1H),4.35(d,J＝17.4Hz,1H),4.23(d,J＝17.5Hz,1H),3.34-3.16(m,6H),3.14-3.00(m,2H),2.98-2.88(m,1H),2.63(d,J＝16.7Hz,1H),2.42-2.29(m,1H),2.08-1.97(m,1H).LCMS(ESI)C₃₀H₃₂N₅O₃ ⁺[M+H]⁺： calculated 510.25, found 510.3) was prepared according to the procedure of scheme 2.

EXAMPLE 287 preparation of Compound GT-09963

The title compound GT-09963 (white solid, 5mg, yield 8％).¹H NMR(400MHz,DMSO-d6)δ11.87(s,1H),11.08(s,1H),8.58(s,1H),7.94(s,3H),7.69-7.43(m,3H),7.33(s,3H),7.16(s,1H),5.73(s,1H),5.07(dd,J＝12.7,5.2Hz,1H),3.33-3.15(m,4H),3.07(s,2H),2.93-2.77(m,2H),2.70-2.53(m,2H),2.46(s,1H),2.06-1.96(m,1H).LCMS(ESI)C₃₀H₂₇F₃N₅O₄ ⁺[M+H]⁺： calculated 600.18, found 600.3) was prepared according to the procedure of scheme 2.

EXAMPLE 288 preparation of Compound GT-09964

The title compound GT-09964 (white solid, 3mg, yield 5％).¹H NMR(400MHz,DMSO-d6)δ11.57(s,1H),10.89(s,1H),8.01-7.54(m,4H),7.38-7.09(m,6H),5.60(s,1H),4.96(dd,J＝13.3,5.1Hz,1H),4.38(d,J＝16.8Hz,1H),4.20(d,J＝16.7Hz,1H),3.19-2.90(m,6H),2.89-2.75(m,2H),2.63-2.48(m,2H),2.37-2.26(m,1H),1.97-1.81(m,1H).LCMS(ESI)C₃₀H₂₉F₃N₅O₃ ⁺[M+H]⁺： calculated 564.22, found 564.3) was prepared according to the procedure of scheme 2.

Example 289 preparation of Compound GT-09965

The title compound GT-09965 (white solid, 11mg, yield 17％).¹H NMR(400MHz,DMSO-d6)δ11.70(s,1H),10.88(s,1H),8.31-7.35(m,5H),7.31-6.85(m,6H),5.63(s,1H),4.97(dd,J＝13.3,5.1Hz,1H),4.24(d,J＝16.9Hz,1H),4.11(d,J＝16.8Hz,1H),3.26-3.04(m,5H),2.98(s,2H),2.86-2.67(m,2H),2.52(d,J＝16.4Hz,1H),2.32-2.24(m,1H),1.95-1.86(m,1H).LCMS(ESI)C₃₀H₂₉F₃N₅O₃ ⁺[M+H]⁺： calculated 564.22, found 564.3) was prepared according to the method of scheme 2.

Example 290 preparation of Compound GT-10076

The title compound GT-10076 (white solid, 11mg, yield 17％).¹H NMR(400MHz,DMSO-d6)δ12.10(s,1H),10.94(s,1H),8.24-7.47(m,5H),7.36-7.13(m,4H),6.62(d,J＝43.5Hz,2H),5.67(s,1H),4.98(dd,J＝13.3,5.1Hz,1H),4.30(d,J＝17.2Hz,1H),4.16(d,J＝17.2Hz,1H),3.34-3.10(m,6H),3.04(s,2H),2.94-2.85(m,1H),2.58(d,J＝16.6Hz,1H),2.35-2.26(m,1H),1.99-1.87(m,1H).LCMS(ESI)C₃₀H₂₉F₃N₅O₃ ⁺[M+H]⁺： calculated 564.22, found 564.3) was prepared according to the method of scheme 2.

EXAMPLE 291 preparation of Compound GT-10077

The title compound GT-10077 (white solid, 7mg, yield 11％).¹H NMR(400MHz,DMSO-d6)δ12.01(s,1H),11.00(s,1H),7.88(s,3H),7.58-6.91(m,9H),5.70(s,1H),5.09(dd,J＝13.2,5.0Hz,1H),4.28(dd,J＝46.0,17.4Hz,2H),3.28-3.16(m,4H),3.09(s,2H),2.97-2.87(m,1H),2.79(s,1H),2.63(d,J＝17.3Hz,1H),2.47-2.19(m,2H),2.10-1.96(m,1H).LCMS(ESI)C₃₀H₃₀F₂N₅O₃ ⁺[M+H]⁺： calculated 546.23, found 546.2) was prepared according to the procedure of scheme 2.

EXAMPLE 292 preparation of Compound GT-10078

The title compound GT-10078 (white solid, 9mg, yield 13％).¹H NMR(400MHz,DMSO-d6)δ11.66(s,1H),10.95(s,1H),8.00-7.72(m,4H),7.55-7.15(m,9H),5.74-5.46(m,1H),5.04(dd,J＝13.2,5.0Hz,1H),4.24(dd,J＝50.0,16.9Hz,2H),3.33-3.25(m,3H),3.25-3.15(m,2H),3.07(s,2H),2.96-2.77(m,2H),2.59(d,J＝16.9Hz,1H),2.40-2.30(m,1H),2.02-1.90(m,1H).LCMS(ESI)C₃₀H₃₁FN₅O₃ ⁺[M+H]⁺： calculated 528.24, found 528.2) was prepared according to the procedure of scheme 2.

EXAMPLE 293 preparation of Compound GT-10079

The title compound GT-10079 (yellow solid, 18mg, yield 28％).¹H NMR(400MHz,DMSO-d6)δ12.14(s,1H),11.09(s,1H),8.74-7.70(m,4H),7.69-7.27(m,7H),5.73(s,1H),5.07(dd,J＝12.8,5.4Hz,1H),3.35-3.15(m,4H),3.05(s,2H),2.93-2.77(m,2H),2.63-2.52(m,2H),2.50-2.43(m,1H),2.06-1.95(m,1H).LCMS(ESI)C₃₀H₂₇Cl₂FN₅O₄ ⁺[M+H]⁺： calculated 610.14, found 610.2) was prepared according to the procedure of FIG. 2.

EXAMPLE 294 preparation of Compound GT-10080

The title compound GT-10080 (white solid, 8mg, yield 13％).¹H NMR(400MHz,DMSO-d6)δ11.86(s,1H),10.95(s,1H),8.06-7.73(m,3H),7.71-7.10(m,8H),5.71(s,1H),5.03(dd,J＝13.3,5.0Hz,1H),4.45(d,J＝16.8Hz,1H),4.27(d,J＝16.7Hz,1H),3.33-3.14(m,4H),3.14-2.96(m,2H),2.94-2.81(m,2H),2.68-2.52(m,2H),2.42-2.32(m,1H),1.99-1.88(m,1H).LCMS(ESI)C₃₀H₂₉Cl₂FN₅O₃ ⁺[M+H]⁺： calculated 596.16, found 596.2) was prepared according to the procedure of scheme 2.

Example 295 preparation of Compound GT-10081

The title compound GT-10081 (white solid, 17mg, yield 27％).¹H NMR(400MHz,DMSO-d6)δ12.04(s,1H),10.95(s,1H),8.07-7.65(m,4H),7.64-7.38(m,5H),7.34(d,J＝10.6Hz,1H),7.23(d,J＝6.9Hz,1H),5.72(s,1H),5.12-4.97(m,1H),4.24(dd,J＝50.6,16.9Hz,2H),3.35-3.13(m,5H),3.04(s,2H),2.96-2.82(m,2H),2.59(d,J＝17.0Hz,1H),2.40-2.29(m,1H),2.02-1.90(m,1H).LCMS(ESI)C₃₀H₂₉Cl₂FN₅O₃ ⁺[M+H]⁺： calculated 596.16, found 596.2) was prepared according to the procedure of scheme 2.

EXAMPLE 296 preparation of Compound GT-10082

The title compound GT-10082 (white solid, 14mg, yield 23％).¹H NMR(400MHz,DMSO-d6)δ12.26(s,1H),10.94(s,1H),8.28-7.70(m,4H),7.71-7.26(m,5H),6.62(d,J＝43.8Hz,2H),5.68(s,1H),4.98(dd,J＝13.3,5.1Hz,1H),4.30(d,J＝17.3Hz,1H),4.16(d,J＝17.3Hz,1H),3.34-3.11(m,5H),3.04(s,2H),2.95-2.70(m,2H),2.58(d,J＝16.7Hz,1H),2.38-2.27(m,1H),2.00-1.86(m,1H).LCMS(ESI)C₃₀H₂₉Cl₂FN₅O₃ ⁺[M+H]⁺： calculated 596.16, found 596.2) was prepared according to the procedure of scheme 2.

Example 297 preparation of Compound GT-10083

The title compound GT-10083 (white solid, 13mg, yield 22％).¹H NMR(400MHz,DMSO-d6)δ12.13(s,1H),11.00(s,1H),7.95(s,3H),7.75-7.39(m,5H),7.29(t,J＝7.6Hz,2H),7.15-6.99(m,2H),5.74(s,1H),5.09(dd,J＝13.2,5.1Hz,1H),4.34(d,J＝17.4Hz,1H),4.23(d,J＝17.5Hz,1H),3.33-3.15(m,5H),3.15-3.02(m,2H),2.99-2.88(m,2H),2.63(d,J＝16.8Hz,1H),2.40-2.30(m,1H),2.10-1.93(m,1H).LCMS(ESI)C₃₀H₃₀Cl₂N₅O₃ ⁺[M+H]⁺： calculated 578.17, found 578.2) was prepared according to the method of scheme 2.

EXAMPLE 298 preparation of Compound GT-10084

The title compound GT-10084 (yellow solid, 25mg, yield 35％).¹H NMR(400MHz,DMSO-d6)δ11.07(s,1H),8.77(d,J＝4.1Hz,1H),8.70-8.40(m,1H),7.98-7.88(m,1H),7.78-7.69(m,3H),7.63(d,J＝8.3Hz,1H),7.50-7.38(m,4H),7.29-7.23(m,1H),7.11-7.01(m,1H),5.89(s,1H),5.05(dd,J＝12.8,5.4Hz,1H),3.38(s,4H),3.18-3.08(m,4H),2.93-2.81(m,1H),2.64-2.53(m,2H),2.07-1.91(m,1H).LCMS(ESI)C₂₉H₂₉N₆O₄ ⁺[M+H]⁺： calculated 525.22, found 525.3) was prepared according to the method of scheme 2.

Example 299 preparation of Compound GT-10085

The title compound GT-10085 (yellow solid, 25mg, yield 34％).¹H NMR(400MHz,DMSO-d6)δ11.09(s,1H),8.76(d,J＝8.6Hz,1H),8.47(s,1H),7.98-7.85(m,1H),7.73(d,J＝7.0Hz,2H),7.71-7.62(m,2H),7.54(d,J＝7.0Hz,1H),7.51-7.40(m,4H),5.88(s,1H),5.07(dd,J＝12.8,5.4Hz,1H),3.39(s,3H),3.26-2.96(m,5H),2.95-2.82(m,1H),2.62-2.52(m,2H),2.08-1.94(m,1H).LCMS(ESI)C₂₉H₂₈FN₆O₄ ⁺[M+H]⁺： calculated 543.22, found 543.3) was prepared according to the method of scheme 2.

Example 300 preparation of Compound GT-10086

The title compound GT-10086 (red solid, 20mg, yield 29％).¹H NMR(400MHz,DMSO-d6)δ10.95(d,J＝11.1Hz,1H),8.76(d,J＝4.1Hz,1H),7.98-7.87(m,1H),7.76-7.69(m,3H),7.49-7.38(m,5H),7.01-6.82(m,2H),5.91(s,1H),5.10-4.98(m,1H),4.30(d,J＝16.9Hz,1H),4.16(d,J＝17.0Hz,1H),3.50-3.30(m,4H),3.21(s,2H),3.09(s,4H),2.94-2.83(m,1H),2.59(d,J＝16.6Hz,1H),2.39-2.25(m,1H),2.01-1.86(m,1H).LCMS(ESI)C₂₉H₃₁N₆O₃ ⁺[M+H]⁺： calculated 511.25, found 511.3) was prepared according to the procedure of scheme 2.

EXAMPLE 301 preparation of Compound GT-10087

The title compound GT-10087 (red solid, 17mg, yield 24％).¹H NMR(400MHz,DMSO-d6)δ10.96(s,1H),8.75(dd,J＝17.3,4.0Hz,1H),7.99-7.87(m,1H),7.71(dd,J＝21.7,7.4Hz,4H),7.49-7.39(m,5H),7.28(dd,J＝14.2,6.4Hz,1H),5.90(s,1H),5.15-4.93(m,1H),4.44(d,J＝15.3Hz,1H),4.26(d,1H),3.37-3.29(m,2H),3.30-3.04(m,6H),2.96-2.84(m,1H),2.62-2.54(m,1H),2.45-2.32(m,1H),2.00-1.92(m,1H).LCMS(ESI)C₂₉H₃₀FN₆O₃ ⁺[M+H]⁺： calculated 529.24, found 529.3) was prepared according to the method of scheme 2.

EXAMPLE 302 preparation of Compound GT-10088

The title compound GT-10088 (red solid, 22mg, yield 31％).¹H NMR(400MHz,DMSO-d6)δ10.96(s,1H),8.75(d,1H),7.97-7.90(m,1H),7.79-7.64(m,4H),7.50-7.40(m,4H),7.35(d,J＝11.3,5.8Hz,1H),7.26(d,J＝7.1Hz,1H),5.90(s,1H),5.10-5.00(m,1H),4.31(d,J＝16.9Hz,1H),4.16(d,1H),3.37-3.29(m,2H),3.27-3.04(m,6H),2.95-2.82(m,1H),2.59(d,J＝17.2Hz,1H),2.40-2.30(m,1H),2.01-1.90(m,1H).LCMS(ESI)C₂₉H₃₀FN₆O₃ ⁺[M+H]⁺： calculated 529.24, found 529.3) was prepared according to the method of scheme 2.

EXAMPLE 303 preparation of Compound GT-10089

The title compound GT-10089 (red solid, 17mg, yield 24％).¹H NMR(400MHz,DMSO-d6)δ10.95(s,1H),8.75(d,J＝7.9Hz,1H),7.93(t,J＝7.7,1.7Hz,1H),7.76-7.70(m,3H),7.49-7.40(m,4H),6.81-6.51(m,2H),5.88(s,1H),4.98(dd,J＝13.3,5.1Hz,1H),4.31(d,J＝17.2Hz,1H),4.17(d,J＝17.2Hz,1H),3.46-3.16(m,5H),3.15-3.02(m,4H),2.93-2.84(m,1H),2.58(d,J＝17.6Hz,1H),2.36-2.25(m,1H),1.99-1.88(m,1H).LCMS(ESI)C₂₉H₃₀FN₆O₃ ⁺[M+H]⁺： calculated 529.24, found 529.3) was prepared according to the procedure of scheme 2.

EXAMPLE 304 preparation of Compound GT-10090

The title compound GT-10090 (red solid, 20mg, yield 29％).¹H NMR(400MHz,DMSO-d6)δ11.02(s,1H),8.75(d,J＝4.1Hz,1H),7.96-7.90(m,1H),7.83-7.75(m,3H),7.50-7.41(m,4H),7.30(t,J＝13.7,6.0Hz,1H),7.13-7.03(m,2H),6.01(s,1H),5.11(dd,J＝13.2,5.0Hz,1H),4.39(d,1H),4.27(d,J＝17.6,2.9Hz,1H),3.38-3.06(m,8H),2.99-2.88(m,1H),2.63(d,J＝16.8Hz,1H),2.47-2.33(m,1H),2.07-1.96(m,1H).LCMS(ESI)C₂₉H₃₁N₆O₃ ⁺[M+H]⁺： calculated 511.25, found 511.3) was prepared according to the procedure of scheme 2.

EXAMPLE 305 preparation of Compound GT-10091

The title compound GT-10091 (yellow solid, 7mg, yield 10％).¹H NMR(400MHz,DMSO-d6)δ12.54(s,1H),11.08(s,1H),9.08(s,1H),8.78-8.33(m,3H),7.94(s,2H),7.71-7.38(m,6H),5.79(s,1H),5.07(dd,J＝12.9,5.3Hz,1H),3.44-3.41(m,2H),3.29-3.15(m,3H),3.11-3.01(m,2H),2.91-2.82(m,1H),2.64-2.53(m,3H),2.07-1.95(m,1H).LCMS(ESI)C₂₉H₂₈FN₆O₄ ⁺[M+H]⁺： calculated 543.22, found 543.3) was prepared according to the procedure of scheme 2.

EXAMPLE 306 preparation of Compound GT-10092

The title compound GT-10092 (white solid, 5mg, yield 6％).¹H NMR(400MHz,DMSO-d6)δ10.95(s,1H),9.07(s,1H),8.91-8.62(m,3H),7.87-7.69(m,2H),7.51-7.37(m,6H),6.08-5.64(m,1H),5.03(dd,J＝13.3,5.0Hz,1H),4.45(d,J＝16.8Hz,1H),4.27(d,J＝16.7Hz,1H),3.19-3.04(m,5H),2.95-2.84(m,2H),2.60-2.54(m,2H),2.40-2.32(m,1H),1.99-1.93(m,1H).LCMS(ESI)C₂₉H₃₀FN₆O₃ ⁺[M+H]⁺： calculated 529.24, found 529.3) was prepared according to the procedure of scheme 2.

EXAMPLE 307 preparation of Compound GT-10093

The title compound GT-10093 (white solid, 7mg, yield 8％).¹H NMR(400MHz,DMSO-d6)δ12.55(s,1H),10.95(s,1H),9.12(s,1H),8.72(d,J＝4.9Hz,2H),8.05-7.64(m,4H),7.47-7.24(m,5H),5.91(d,J＝79.9Hz,1H),5.04(dd,J＝13.3,5.1Hz,1H),4.31(d,J＝16.9Hz,1H),4.18(d,J＝16.8Hz,1H),3.34-3.17(m,5H),3.06(s,3H),2.94-2.86(m,1H),2.59(d,J＝16.6Hz,1H),2.38-2.29(m,1H),2.00-1.91(m,1H).LCMS(ESI)C₂₉H₃₀FN₆O₃ ⁺[M+H]⁺： calculated 529.24, found 529.3) was prepared according to the method of scheme 2.

EXAMPLE 308 preparation of Compound GT-10496

The title compound GT-10496 (white solid, 12mg, yield 13％).¹H NMR(400MHz,DMSO-d6)δ12.81(s,1H),10.94(s,1H),8.84-8.72(m,2H),8.12-7.96(m,2H),7.77(s,1H),7.52-7.38(m,4H),6.84-6.50(m,2H),5.84(s,1H),4.98(dd,J＝13.3,5.0Hz,1H),4.30(d,J＝17.2Hz,1H),4.16(d,J＝17.2Hz,1H),3.49-3.12(m,7H),3.05(s,2H),2.94-2.84(m,1H),2.57(d,J＝17.1Hz,1H),2.40-2.22(m,1H),2.04-1.86(m,1H).LCMS(ESI)C₂₉H₃₀FN₆O₃ ⁺[M+H]⁺： calculated 529.24, found 529.3) was prepared according to the procedure of FIG. 2.

EXAMPLE 309 preparation of Compound GT-10094

The title compound GT-10094 (white solid, 14mg, yield 15％).¹H NMR(400MHz,DMSO-d6)δ12.81(s,1H),10.99(s,1H),8.93-8.73(m,3H),8.03-7.93(m,2H),7.84-7.74(m,1H),7.43-7.34(m,3H),7.31-7.25(m,2H),7.12(t,J＝7.7Hz,1H),7.04(d,J＝5.8Hz,1H),6.02(s,1H),5.10(dd,J＝13.2,5.1Hz,1H),4.36(d,J＝18.6Hz,1H),4.24(d,J＝17.6Hz,1H),3.38-3.20(m,6H),3.08(s,2H),2.97-2.89(m,1H),2.63(d,J＝16.9Hz,1H),2.44-2.36(m,1H),2.07-1.99(m,1H).LCMS(ESI)C₂₉H₃₁N₆O₃ ⁺[M+H]⁺： calculated 511.25, found 511.3) was prepared according to the procedure of scheme 2.

EXAMPLE 310 preparation of Compound GT-10166

The title compound GT-10166 (white solid, 28mg, yield 39％).¹H NMR(400MHz,DMSO-d6)δ11.06(s,1H),10.87(s,1H),8.42(s,1H),8.13(d,J＝5.5Hz,1H),7.62-7.51(m,5H),7.43-7.37(m,2H),7.36-7.28(m,1H),7.18(s,1H),7.01(d,J＝7.1Hz,1H),5.10-4.95(m,1H),4.29(s,2H),3.24(d,J＝7.6Hz,2H),3.18-2.91(m,6H),2.91-2.84(m,1H),2.60-2.52(m,2H),2.05-1.92(m,1H).LCMS(ESI)C₃₀H₂₉ClN₅O₄ ⁺[M+H]⁺： calculated 558.19, found 558.2) was prepared according to the procedure described in scheme 1.

EXAMPLE 311 preparation of Compound GT-10167

The title compound GT-10167 (white solid, 30mg, yield 41％).¹H NMR(400MHz,DMSO-d6)δ11.08(s,1H),10.58(s,1H),8.42(s,1H),8.11(t,J＝14.7Hz,1H),7.65-7.46(m,6H),7.40(d,J＝8.3Hz,2H),7.36-7.30(m,1H),5.06(dd,J＝12.8,5.4Hz,1H),4.31(d,J＝33.0Hz,2H),3.25(d,J＝9.4Hz,2H),3.07(d,J＝47.1Hz,4H),3.00-2.82(m,3H),2.55(dd,J＝18.5,11.9Hz,2H),2.06-1.92(m,1H).LCMS(ESI)C₃₀H₂₈ClFN₅O₄ ⁺[M+H]⁺： calculated 576.18, found 576.2) was prepared according to the procedure of scheme 1.

Example 312 preparation of Compound GT-10168

The title compound GT-10168 (white solid, 20mg, yield 28％).¹H NMR(400MHz,DMSO-d6)δ10.95(s,1H),10.64(s,1H),8.07(d,J＝5.5Hz,1H),7.73(s,1H),7.61-7.49(m,4H),7.45-7.30(m,4H),7.24(t,J＝7.7Hz,1H),5.03(dd,J＝13.3,5.0Hz,1H),4.49-4.20(m,4H),3.24(d,J＝11.0Hz,2H),3.15-3.04(m,2H),3.03-2.84(m,5H),2.58(d,J＝17.8Hz,1H),2.44-2.31(m,1H),2.01-1.89(m,1H).LCMS(ESI)C₃₀H₃₀ClFN₅O₃ ⁺[M+H]⁺： calculated 562.20, found 562.3) was prepared according to the procedure of scheme 1.

EXAMPLE 313 preparation of Compound GT-10169

The title compound GT-10169 (white solid, 22mg, yield 30％).¹H NMR(400MHz,DMSO-d6)δ10.95(s,1H),10.70(s,1H),8.09(d,J＝5.3Hz,1H),7.72(s,1H),7.63-7.49(m,4H),7.40(d,J＝8.4Hz,2H),7.37-7.28(m,2H),7.21(d,J＝7.2Hz,1H),5.03(dd,J＝13.3,5.1Hz,1H),4.46-4.09(m,4H),3.32-3.07(m,4H),3.06-2.83(m,5H),2.56(s,1H),2.44-2.25(m,1H),2.01-1.87(m,1H).LCMS(ESI)C₃₀H₃₀ClFN₅O₃ ⁺[M+H]⁺： calculated 562.20, found 562.3) was prepared according to the procedure of scheme 1.

Example 314 preparation of Compound GT-10170

The title compound GT-10170 (white solid, 23mg, yield 32％).¹H NMR(400MHz,DMSO-d6)δ10.94(s,1H),10.81(s,1H),8.11(s,1H),8.00(s,1H),7.61-7.52(m,4H),7.43-7.37(m,2H),7.36-7.29(m,1H),6.64(s,1H),6.57(d,J＝12.1Hz,1H),4.97(dd,J＝13.3,5.1Hz,1H),4.36-4.10(m,4H),3.23(d,J＝7.5Hz,2H),3.09-2.83(m,7H),2.61-2.53(m,1H),2.37-2.25(m,1H),1.98-1.88(m,1H).LCMS(ESI)C₃₀H₃₀ClFN₅O₃ ⁺[M+H]⁺： calculated 562.20, found 562.2) was prepared according to the procedure of scheme 1.

EXAMPLE 315 preparation of Compound GT-10171

The title compound GT-10171 (white solid, 26mg, yield 37％).¹H NMR(400MHz,DMSO-d6)δ10.97(d,J＝21.5Hz,2H),8.11(s,1H),7.58-7.50(m,4H),7.41(d,J＝8.4Hz,2H),7.36-7.25(m,2H),7.19(s,1H),7.05(t,J＝7.5Hz,2H),5.12-5.00(m,1H),4.36-4.08(m,4H),3.27-3.18(m,2H),3.11-2.82(m,8H),2.63(d,J＝16.8Hz,2H),2.34-2.23(m,1H),2.06-1.93(m,1H).LCMS(ESI)C₃₀H₃₁ClN₅O₃ ⁺[M+H]⁺： calculated 544.21, found 544.3) was prepared according to the procedure described in scheme 1.

EXAMPLE 316 preparation of Compound GT-10172

The title compound GT-10172 (white solid, 5mg, yield 8％).¹H NMR(400MHz,DMSO-d6)δ10.95(s,1H),7.95-7.87(m,1H),7.58-7.51(m,4H),7.44-7.37(m,4H),7.32-7.26(m,1H),7.11(d,2H),5.05(dd,J＝13.3,5.1Hz,1H),4.39-4.18(m,2H),3.60-3.57(m,2H),3.50-3.46(m,4H),3.23-3.13(m,4H),2.96-2.84(m,1H),2.59(d,J＝16.9Hz,1H),2.44-2.30(m,1H),2.04-1.91(m,1H).LCMS(ESI)C₃₀H₂₉ClN₅O₃ ⁺[M+H]⁺： calculated 542.20, found 542.3) was prepared according to the procedure of scheme 1.

EXAMPLE 317 preparation of Compound GT-10173

The title compound GT-10173 (white solid, 17mg, yield 23％).¹H NMR(400MHz,DMSO-d6)δ11.09(s,1H),11.01(s,1H),8.50(s,1H),8.03(s,1H),7.78(d,J＝8.5Hz,3H),7.64(d,J＝10.2Hz,1H),7.61-7.53(m,5H),5.08(dd,J＝12.8,5.4Hz,1H),4.42(d,J＝3.9Hz,2H),3.42-3.37(m,4H),3.24-3.09(m,4H),2.92-2.83(m,1H),2.64-2.52(m,2H),2.06-1.97(m,1H).LCMS(ESI)C₃₀H₂₈ClFN₅O₄ ⁺[M+H]⁺： calculated 576.18, found 576.2) was prepared according to the procedure of scheme 1.

EXAMPLE 318 preparation of Compound GT-10174

The title compound GT-10174 (white solid, 16mg, yield 23％).¹H NMR(400MHz,DMSO-d6)δ10.96(s,2H),8.01(s,1H),7.78(d,J＝8.5Hz,4H),7.65-7.54(m,4H),7.42(d,J＝8.2Hz,1H),7.30(t,J＝7.7Hz,1H),5.04(dd,J＝13.3,5.1Hz,1H),4.44(t,J＝13.1Hz,3H),4.28(d,J＝16.7Hz,1H),3.39(s,2H),3.30(s,2H),3.09(s,4H),2.95-2.85(m,1H),2.59(d,J＝17.4Hz,1H),2.46-2.31(m,1H),2.02-1.90(m,1H).LCMS(ESI)C₃₀H₃₀ClFN₅O₃ ⁺[M+H]⁺： calculated 562.20, found 562.2) was prepared according to the procedure of scheme 1.

Example 319 preparation of Compound GT-10175

The title compound GT-10175 (white solid, 15mg, yield 21％).¹H NMR(400MHz,DMSO-d6)δ11.05(s,1H),10.96(s,1H),8.03(s,1H),7.78(d,J＝8.3Hz,4H),7.65-7.54(m,4H),7.35(d,J＝10.6Hz,1H),7.26(d,J＝7.2Hz,1H),5.05(dd,J＝13.3,5.1Hz,1H),4.41(s,2H),4.25(dd,J＝49.7,16.9Hz,2H),3.43-3.39(m,2H),3.31-3.24(m,2H),3.17-3.02(m,4H),2.96-2.85(m,1H),2.59(d,J＝17.2Hz,1H),2.41-2.30(m,1H),2.01-1.91(m,1H).LCMS(ESI)C₃₀H₃₀ClFN₅O₃ ⁺[M+H]⁺： calculated 562.20, found 562.2) was prepared according to the procedure of scheme 1.

EXAMPLE 320 preparation of Compound GT-10176

The title compound GT-10176 (white solid, 14mg, yield 20％).¹H NMR(400MHz,DMSO-d6)δ11.09(s,1H),10.95(s,1H),8.04(d,J＝13.4Hz,2H),7.79(d,J＝8.5Hz,3H),7.63-7.54(m,4H),6.69(s,1H),6.60(d,J＝11.9Hz,1H),4.99(dd,J＝13.3,5.1Hz,1H),4.40(s,2H),4.24(dd,J＝55.1,17.3Hz,2H),3.43-3.38(m,2H),3.31-3.23(m,2H),3.12-2.96(m,4H),2.94-2.84(m,1H),2.58(d,J＝17.3Hz,1H),2.37-2.26(m,1H),1.98-1.90(m,1H).LCMS(ESI)C₃₀H₃₀ClFN₅O₃ ⁺[M+H]⁺： calculated 562.20, found 562.2) was prepared according to the procedure of scheme 1.

Example 321 preparation of Compound GT-10177

The title compound GT-10177 (white solid, 13mg, yield 19％).¹H NMR(400MHz,DMSO-d6)δ11.18(s,1H),11.00(s,1H),7.99(s,1H),7.82-7.74(m,3H),7.66-7.53(m,4H),7.34-7.23(m,2H),7.08(dd,J＝13.1,7.6Hz,2H),5.09(dd,J＝13.3,5.0Hz,1H),4.46-4.17(m,4H),3.33-3.17(m,4H),3.16-2.98(m,4H),2.97-2.87(m,1H),2.61(d,J＝17.1Hz,1H),2.42-2.28(m,1H),2.07-1.94(m,1H).LCMS(ESI)C₃₀H₃₁ClN₅O₃ ⁺[M+H]⁺： calculated 544.21, found 544.3) was prepared according to the procedure of scheme 1.

Example 322 preparation of Compound GT-10178

The title compound GT-10178 (white solid, 14mg, yield 19％).¹H NMR(400MHz,DMSO-d6)δ11.09(s,1H),10.90(s,1H),8.49(s,1H),7.85-7.69(m,6H),7.65(d,J＝10.2Hz,1H),7.60-7.51(m,3H),5.14-5.00(m,1H),4.40(s,2H),3.51-3.39(m,3H),3.12(s,4H),2.93-2.83(m,1H),2.64-2.54(m,2H),2.50-2.44(m,1H),2.08-1.96(m,1H).LCMS(ESI)C₃₀H₂₈ClFN₅O₄ ⁺[M+H]⁺： calculated 576.18, found 576.2) was prepared according to the procedure of scheme 1.

EXAMPLE 323 preparation of Compound GT-10179

The title compound GT-10179 (white solid, 19mg, yield 27％).¹H NMR(400MHz,DMSO-d6)δ10.96(s,1H),10.87(s,1H),7.86-7.68(m,7H),7.58-7.51(m,2H),7.42(d,J＝8.2Hz,1H),7.30(t,J＝7.7Hz,1H),5.04(dd,J＝13.3,5.1Hz,1H),4.52-4.24(m,4H),3.44-3.39(m,2H),3.31-3.23(m,2H),3.09(s,4H),2.98-2.84(m,1H),2.59(d,J＝17.0Hz,1H),2.44-2.31(m,1H),2.02-1.91(m,1H).LCMS(ESI)C₃₀H₃₀ClFN₅O₃ ⁺[M+H]⁺： calculated 562.20, found 562.3) was prepared according to the procedure of scheme 1.

EXAMPLE 324 preparation of Compound GT-10180

The title compound GT-10180 (white solid, 26mg, yield 36％).¹H NMR(400MHz,DMSO-d6)δ10.96(s,1H),10.91(s,1H),7.83-7.70(m,7H),7.55(d,J＝8.6Hz,2H),7.36(d,J＝10.6Hz,1H),7.26(d,J＝7.2Hz,1H),5.05(dd,J＝13.3,5.1Hz,1H),4.39(s,2H),4.34-4.14(m,2H),3.53-3.43(m,2H),3.27(s,2H),3.10(s,4H),2.97-2.86(m,1H),2.59(d,J＝16.6Hz,1H),2.44-2.29(m,1H),2.04-1.91(m,1H).LCMS(ESI)C₃₀H₃₀ClFN₅O₃ ⁺[M+H]⁺： calculated 562.20, found 562.3) was prepared according to the procedure of scheme 1.

EXAMPLE 325 preparation of Compound GT-10181

The title compound GT-10181 (white solid, 32mg, yield 44％).¹H NMR(400MHz,DMSO-d6)δ11.13(s,1H),10.95(s,1H),8.07(s,1H),7.82-7.71(m,6H),7.55(d,J＝8.6Hz,2H),6.69(s,1H),6.61(d,J＝12.0Hz,1H),4.99(dd,J＝13.3,5.1Hz,1H),4.36(s,2H),4.33-4.12(m,2H),3.43-3.38(m,2H),3.32-3.20(m,2H),3.16-2.95(m,4H),2.94-2.84(m,1H),2.58(d,J＝17.0Hz,1H),2.39-2.23(m,1H),1.99-1.88(m,1H).LCMS(ESI)C₃₀H₃₀ClFN₅O₃ ⁺[M+H]⁺： calculated 562.20, found 562.3) was prepared according to the procedure of scheme 1.

EXAMPLE 326 preparation of Compound GT-10182

The title compound GT-10182 (white solid, 27mg, yield 39％).¹H NMR(400MHz,DMSO-d6)δ11.18(s,1H),11.01(s,1H),7.82-7.73(m,6H),7.58-7.51(m,2H),7.34-7.23(m,2H),7.09(dd,J＝15.2,7.5Hz,2H),5.10(dd,J＝13.3,5.1Hz,1H),4.44-4.18(m,4H),3.41-3.38(m,2H),3.29-3.19(m,2H),3.16-2.98(m,4H),2.98-2.86(m,1H),2.62(d,J＝17.1Hz,1H),2.44-2.32(m,1H),2.09-1.94(m,1H).LCMS(ESI)C₃₀H₃₁ClN₅O₃ ⁺[M+H]⁺： calculated 544.21, found 544.3) was prepared according to the procedure of scheme 1.

EXAMPLE 327 preparation of Compound GT-10183

The title compound GT-10183 (white solid, 23mg, yield 33％).¹H NMR(400MHz,DMSO-d6)δ11.25(s,1H),11.01(s,1H),9.36(d,J＝1.4Hz,1H),9.02(d,J＝1.4Hz,1H),8.21(d,J＝7.9,1.7Hz,2H),7.65-7.52(m,3H),7.30(t,J＝7.7Hz,1H),7.08(dd,J＝10.6,7.7Hz,2H),5.10(dd,J＝13.3,5.1Hz,1H),4.65(s,2H),4.37(d,J＝17.5Hz,1H),4.24(d,J＝17.5Hz,1H),3.58-3.50(m,4H),3.14(d,J＝11.4Hz,2H),3.01(s,2H),2.97-2.87(m,1H),2.62(d,J＝17.2Hz,1H),2.45-2.31(m,1H),2.09-1.97(m,1H).LCMS(ESI)C₂₈H₃₀N₇O₃ ⁺[M+H]⁺： calculated 512.24, found 512.3) was prepared according to the procedure of scheme 2.

EXAMPLE 328 preparation of Compound GT-10207

The title compound GT-10207 (white solid, 30mg, yield 42％).¹H NMR(400MHz,DMSO-d6)δ12.11(s,1H),11.07(s,1H),9.29(s,1H),9.15-9.03(m,2H),8.86-8.37(m,4H),7.63(d,J＝8.3Hz,1H),7.23(d,J＝3.9Hz,1H),7.11-6.93(m,1H),5.05(dd,J＝12.8,5.4Hz,1H),4.55(s,2H),4.21-4.11(m,2H),3.39(s,3H),3.27-3.07(m,4H),3.03-2.82(m,2H),2.58(d,J＝17.4Hz,1H),2.06-1.95(m,1H).LCMS(ESI)C₂₈H₂₈N₇O₄ ⁺[M+H]⁺： calculated 526.22, found 526.2) was prepared according to the procedure of scheme 2.

Example 329 preparation of Compound GT-10208

The title compound GT-10208 (white solid, 29mg, yield 40％).¹H NMR(400MHz,DMSO-d6)δ11.75(s,1H),11.09(s,1H),9.38-8.85(m,3H),8.81-8.22(m,4H),7.64(d,J＝10.2Hz,1H),7.56(t,J＝6.8Hz,1H),5.07(dd,J＝12.8,5.4Hz,1H),4.53(s,1H),3.43-3.33(m,5H),3.29-3.19(m,3H),3.13-3.09(m,1H),3.03(s,1H),2.94-2.85(m,1H),2.59(d,J＝19.2Hz,1H),2.05-1.97(m,1H).LCMS(ESI)C₂₈H₂₇FN₇O₄ ⁺[M+H]⁺： calculated 544.21, found 544.2) was prepared according to the procedure of scheme 2.

EXAMPLE 330 preparation of Compound GT-10209

The title compound GT-10209 (white solid, 17mg, yield 25％).¹H NMR(400MHz,DMSO-d6)δ11.98(s,1H),10.94(s,1H),9.16-9.01(m,3H),8.71(t,J＝7.7Hz,2H),8.57-8.44(m,2H),7.46(d,J＝8.3Hz,1H),6.94(s,1H),6.88(d,J＝8.4Hz,1H),5.03(dd,J＝13.3,5.1Hz,1H),4.54(s,2H),4.30(d,J＝16.9Hz,1H),4.17(d,J＝16.9Hz,1H),3.41-3.27(m,5H),3.10(s,4H),2.95-2.86(m,1H),2.59(d,J＝16.8Hz,1H),2.39-2.31(m,1H),1.99-1.91(m,1H).LCMS(ESI)C₂₈H₃₀N₇O₃ ⁺[M+H]⁺： calculated 512.24, found 512.3) was prepared according to the procedure of FIG. 2.

EXAMPLE 331 preparation of Compound GT-10210

The title compound GT-10210 (white solid, 24mg, yield 34％).¹H NMR(400MHz,DMSO-d6)δ11.85(s,1H),10.96(s,1H),9.10-9.03(m,2H),8.69(d,J＝6.6Hz,2H),8.52(d,J＝8.2Hz,1H),8.50-8.43(m,1H),7.82(s,1H),7.44-7.38(m,1H),7.34-7.26(m,1H),5.04(dd,J＝13.3,5.1Hz,1H),4.53(s,2H),4.45(d,J＝16.8Hz,1H),4.27(d,J＝16.8Hz,1H),3.42-3.32(m,3H),3.23-3.15(m,2H),3.13-3.03(m,2H),3.03-2.95(m,1H),2.94-2.85(m,1H),2.62-2.54(m,1H),2.46-2.36(m,1H),2.01-1.90(m,1H).LCMS(ESI)C₂₈H₂₉FN₇O₃ ⁺[M+H]⁺： calculated 530.23, found 530.3) was prepared according to the procedure of FIG. 2.

EXAMPLE 332 preparation of Compound GT-10211

The title compound GT-10211 (white solid, 18mg, yield 26％).¹H NMR(400MHz,DMSO-d6)δ11.83(s,1H),10.96(s,1H),9.10-9.04(m,2H),8.78-8.62(m,2H),8.53-8.47(m,1H),7.82(s,1H),7.33(dd,J＝12.1,9.1Hz,1H),7.28(d,J＝7.0Hz,1H),5.05(dd,J＝13.3,5.1Hz,1H),4.54(s,2H),4.32(d,J＝16.9Hz,1H),4.20(d,J＝16.9Hz,1H),3.44-3.29(m,4H),3.22-3.14(m,2H),3.13-3.02(m,2H),2.96-2.86(m,1H),2.59(d,J＝17.2Hz,1H),2.40-2.30(m,1H),2.00-1.92(m,1H).LCMS(ESI)C₂₈H₂₉FN₇O₃ ⁺[M+H]⁺： calculated 530.23, found 530.3) was prepared according to the procedure of FIG. 2.

EXAMPLE 333 preparation of Compound GT-10212

The title compound GT-10212 (white solid, 21mg, yield 30％).¹H NMR(400MHz,DMSO-d6)δ12.06(s,1H),10.95(s,1H),9.24(s,1H),9.11-9.04(m,2H),8.71-8.68(m,1H),8.52(d,J＝8.2Hz,1H),8.49-8.39(m,1H),8.34-7.86(m,1H),6.84-6.47(m,2H),4.99(dd,J＝13.3,5.1Hz,1H),4.49(s,2H),4.29(d,1H),4.17(d,J＝17.3Hz,1H),3.42-3.29(m,3H),3.21(s,1H),3.09(s,3H),3.00-2.83(m,2H),2.58(d,J＝17.5Hz,1H),2.38-2.24(m,1H),2.00-1.89(m,1H).LCMS(ESI)C₂₈H₂₉FN₇O₃ ⁺[M+H]⁺： calculated 530.23, found 530.3) was prepared according to the procedure of FIG. 2.

Example 334 preparation of Compound GT-10296

The title compound GT-10296 (white solid, 25mg, yield 36％).¹H NMR(400MHz,DMSO-d6)δ12.15(s,1H),11.00(s,1H),9.37(s,1H),9.14(s,1H),9.08(d,J＝6.6Hz,2H),8.76(d,J＝6.6Hz,2H),8.57-8.51(m,2H),7.32-7.28(m,1H),7.08(dd,J＝19.0,7.8Hz,3H),5.12-5.09(m,1H),4.56(s,2H),4.37-4.34(m,1H),4.27-4.25(m,1H),3.36(s,3H),3.12(s,4H),2.99-2.93(m,2H),2.62(d,J＝16.7Hz,1H),2.45-2.38(m,1H),2.05-1.99(m,1H).LCMS(ESI)C₂₈H₃₀N₇O₃ ⁺[M+H]⁺： calculated 512.24, found 512.3) was prepared according to the procedure of scheme 2.

EXAMPLE 335 preparation of Compound GT-10297

The title compound GT-10297 (white solid, 27mg, yield 33％).¹H NMR(400MHz,DMSO-d6)δ11.30(s,1H),11.07(s,1H),8.47(s,1H),7.75(s,1H),7.63(d,J＝8.3Hz,1H),7.37(s,2H),7.22(s,1H),7.09-6.98(m,1H),6.84(d,J＝2.6Hz,1H),6.70-6.53(m,1H),5.05(dd,J＝12.9,5.4Hz,1H),4.59(s,2H),3.46-3.38(m,2H),3.32-3.21(m,2H),3.14(d,J＝11.4Hz,2H),3.04(s,2H),2.93-2.84(m,1H),2.62-2.52(m,2H),2.04-1.91(m,1H).LCMS(ESI)C₂₆H₂₅N₅NaO₅S⁺[M+H]⁺： calculated 542.15, found 542.2) was prepared according to the method of scheme 1.

EXAMPLE 336 preparation of Compound GT-10298

The title compound GT-10298 (white solid, 33mg, yield 39％).¹H NMR(400MHz,DMSO-d6)δ11.17(s,1H),11.09(s,1H),8.49(s,1H),7.75(s,1H),7.64(d,J＝10.2Hz,1H),7.54(d,J＝6.9Hz,1H),7.38(d,J＝6.2Hz,2H),6.84(d,J＝2.8Hz,1H),6.62(s,1H),5.16-4.99(m,1H),4.58(s,2H),3.45-3.37(m,4H),3.13(s,4H),2.94-2.84(m,1H),2.62-2.53(m,2H),2.06-1.95(m,1H).LCMS(ESI)C₂₆H₂₄FN₅NaO₅S⁺[M+H]⁺： calculated 560.14, found 560.2) was prepared according to the procedure of scheme 1.

EXAMPLE 337 preparation of Compound GT-10299

The title compound GT-10299 (white solid, 24mg, yield 30％).¹H NMR(400MHz,DMSO-d6)611.30(s,1H),10.94(s,1H),7.85-7.62(m,2H),7.46(d,J＝8.3Hz,1H),7.43-7.33(m,2H),6.93(s,1H),6.88-6.81(m,2H),6.65-6.60(m,1H),5.10-4.97(m,1H),4.58(s,2H),4.28(d,J＝12.5Hz,1H),4.16(d,J＝16.9Hz,1H),3.47-3.42(m,2H),3.29-3.17(m,2H),3.12(d,J＝11.0Hz,2H),3.04-2.94(m,2H),2.93-2.83(m,1H),2.61-2.54(m,1H),2.41-2.28(m,1H),2.00-1.90(m,1H).LCMS(ESI)C₂₆H₂₈N₅O₄S⁺[M+H]⁺： calculated 506.19, found 506.2) was prepared according to the procedure of scheme 1.

EXAMPLE 338 preparation of Compound GT-10300

The title compound GT-10300 (white solid, 24mg, yield 29％).¹H NMR(400MHz,DMSO-d6)δ11.10(s,1H),10.96(s,1H),7.75(s,2H),7.47-7.34(m,3H),7.29(t,J＝7.7Hz,1H),6.85(d,J＝3.1Hz,1H),6.676.53(m,1H),5.04(dd,J＝13.3,5.0Hz,1H),4.58(s,2H),4.45(d,J＝16.8Hz,1H),4.28(d,J＝16.8Hz,1H),3.46-3.40(m,2H),3.24(s,2H),3.10(s,4H),2.95-2.85(m,1H),2.59(d,J＝17.0Hz,1H),2.47-2.31(m,1H),2.01-1.88(m,1H).LCMS(ESI)C₂₆H₂₇FN₅O₄S⁺[M+H]⁺： calculated 524.18, found 524.3) was prepared according to the procedure of scheme 1.

EXAMPLE 339 preparation of Compound GT-10301

The title compound GT-10301 (white solid, 21mg, yield 25.15％).¹H NMR(400MHz,DMSO-d6)δ11.11(s,1H),10.96(s,1H),7.86-7.59(m,2H),7.48-7.30(m,3H),7.25(d,J＝7.1Hz,1H),6.85(d,J＝2.9Hz,1H),6.62(s,1H),5.05(dd,J＝13.3,5.0Hz,1H),4.59(s,2H),4.31(d,J＝16.9Hz,1H),4.19(d,J＝16.9Hz,1H),3.46-3.40(m,2H),3.23(s,2H),3.11(s,4H),2.95-2.85(m,1H),2.62-2.54(m,1H),2.41-2.27(m,1H),2.05-1.90(m,1H).LCMS(ESI)C₂₆H₂₇FN₅O₄S⁺[M+H]⁺： calculated 524.18, found 524.3) was prepared according to the procedure of scheme 1.

EXAMPLE 340 preparation of Compound GT-10302

The title compound GT-10302 (white solid, 21mg, yield 26％).¹H NMR(400MHz,DMSO-d6)δ11.24(s,1H),10.95(s,1H),8.06(s,1H),7.75(s,1H),7.37(s,2H),6.84(d,J＝3.2Hz,1H),6.75-6.55(m,3H),4.99(dd,J＝13.3,5.1Hz,1H),4.58(s,2H),4.31(d,J＝17.3Hz,1H),4.17(d,J＝17.2Hz,1H),3.44-3.39(m,2H),3.26(s,2H),3.11(d,J＝11.1Hz,2H),2.97(d,J＝18.6Hz,2H),2.93-2.83(m,1H),2.58(d,J＝17.4Hz,1H),2.39-2.25(m,1H),2.00-1.87(m,1H).LCMS(ESI)C₂₆H₂₇FN₅O₄S⁺[M+H]⁺： calculated 524.18, found 524.2) was prepared according to the procedure of scheme 1.

EXAMPLE 341 preparation of Compound GT-10303

The title compound GT-10303 (white solid, 36mg, yield 45％).¹H NMR(400MHz,DMSO-d6)δ11.38(s,1H),11.00(s,1H),7.75(s,1H),7.43-7.34(m,2H),7.34-7.19(m,2H),7.14-7.00(m,2H),6.84(d,J＝3.3Hz,1H),6.69-6.52(m,1H),5.09(dd,J＝13.2,5.0Hz,1H),4.58(s,2H),4.35(d,J＝17.4Hz,1H),4.22(d,J＝17.4Hz,1H),3.37-3.18(m,4H),3.13(d,2H),3.09-2.99(m,2H),2.98-2.86(m,1H),2.66-2.55(m,1H),2.43-2.29(m,1H),2.10-1.94(m,1H).LCMS(ESI)C₂₆H₂₈N₅O₄S⁺[M+H]⁺： calculated 506.19, found 506.2) was prepared according to the procedure of scheme 1.

EXAMPLE 342 preparation of Compound GT-10304

The title compound GT-10304 (white solid, 26mg, yield 41％).¹H NMR(400MHz,DMSO-d6)δ10.98(s,1H),7.56-7.51(m,3H),7.49-7.41(m,4H),7.41-7.31(m,2H),7.25(t,J＝7.7Hz,1H),7.02(dd,J＝7.5,5.0Hz,2H),5.07(dd,J＝13.3,5.0Hz,1H),4.26(dd,J＝40.1,17.4Hz,2H),3.16(s,1H),3.05-2.81(m,3H),2.78-2.64(m,2H),2.64-2.51(m,4H),2.42-2.31(m,1H),2.04-1.94(m,1H).LCMS(ESI)C₃₀H₂₉ClN₅O₄ ⁺[M+H]⁺： calculated 558.19, found 558.3) was prepared according to the procedure of scheme 3.

EXAMPLE 343 preparation of Compound GT-10305

The title compound GT-10305 (white solid, 20mg, yield 28％).¹H NMR(400MHz,DMSO-d6)δ11.00(s,1H),10.37(s,1H),7.26(dd,J＝15.8,8.1Hz,2H),7.23-7.18(m,4H),7.10-7.01(m,2H),5.08(dd,J＝13.3,5.0Hz,1H),4.29(d,J＝17.5Hz,1H),4.16(d,J＝17.4Hz,1H),3.54(s,2H),3.36-3.31(m,2H),3.17-3.04(m,2H),3.01-2.72(m,5H),2.62(d,J＝17.0Hz,1H),2.39-2.22(m,5H),2.08-1.97(m,1H),1.70(s,4H).LCMS(ESI)C₃₀H₃₅FN₅O₃ ⁺[M+H]⁺： calculated 532.27, found 532.3) was prepared according to the procedure of scheme 1.

EXAMPLE 344 preparation of Compound GT-10306

The title compound GT-10306 (white solid, 15mg, yield 21％).¹H NMR(400MHz,DMSO-d6)δ10.95(s,1H),10.36(s,1H),7.74(s,1H),7.50(d,J＝8.2Hz,2H),7.33(d,J＝10.6Hz,1H),7.27(d,J＝8.3Hz,2H),7.22(d,J＝7.2Hz,1H),5.03(dd,J＝13.3,5.0Hz,1H),4.38(s,2H),4.28(d,J＝16.9Hz,1H),4.15(d,J＝16.9Hz,1H),3.84(t,J＝5.3Hz,2H),3.66(s,2H),3.38(s,2H),3.16(s,2H),2.97-2.79(m,5H),2.58(d,J＝17.7Hz,1H),2.40-2.26(m,3H),2.02-1.82(m,1H).LCMS(ESI)C₂₉H₃₂ClFN₅O₄ ⁺[M+H]⁺： calculated 568.21, found 568.3) was prepared according to the procedure of scheme 1.

EXAMPLE 345 preparation of Compound GT-10307

The title compound GT-10307 (white solid, 25mg, yield 36％).¹H NMR(400MHz,DMSO-d6)611.00(s,1H),10.78(s,1H),7.55-7.44(m,2H),7.32-7.25(m,3H),7.06(dd,J＝14.8,7.6Hz,2H),5.08(dd,J＝13.2,5.0Hz,1H),4.41(q,J＝16.7Hz,2H),4.29(d,J＝17.5Hz,1H),4.16(d,J＝17.4Hz,1H),3.83(t,J＝5.4Hz,2H),3.63(s,2H),3.37-3.33(m,2H),3.20-3.05(m,2H),3.04-2.71(m,5H),2.63(d,J＝16.7Hz,1H),2.45-2.25(m,3H),2.07-1.95(m,1H).LCMS(ESI)C₂₉H₃₃ClN₅O₄ ⁺[M+H]⁺： calculated 550.22, found 550.3) was prepared according to the procedure of scheme 1.

Example 346 preparation of Compound GT-10308

The title compound GT-10308 (white solid, 18mg, yield 27％).¹H NMR(400MHz,DMSO-d6)δ12.31(s,1H),11.06(s,1H),8.80-7.83(m,2H),7.61(d,J＝8.3Hz,1H),7.57-6.82(m,7H),6.20(s,1H),5.13-4.93(m,1H),3.60(s,1H),3.42-3.10(m,5H),3.05(s,1H),2.96-2.68(m,2H),2.66-2.53(m,2H),2.49-2.19(m,1H),2.06-1.93(m,1H).LCMS(ESI)C₃₀H₂₈F₂N₅O₄ ⁺[M+H]⁺： calculated 560.21, found 560.3) was prepared according to the procedure of FIG. 2.

EXAMPLE 347 preparation of Compound GT-10309

The title compound GT-10309 (white solid, 3mg, yield 5％).¹H NMR(400MHz,DMSO-d6)δ11.08(s,1H),8.23(s,2H),7.78-6.92(m,9H),5.06(dd,J＝12.8,5.3Hz,1H),3.42(s,2H),3.32-3.11(m,3H),3.09-2.77(m,5H),2.68-2.55(m,2H),2.07-1.97(m,1H).LCMS(ESI)C₃₀H₂₇F₃N₅O₄ ⁺[M+H]⁺： calculated 578.20, found 578.3) was prepared according to the procedure of FIG. 2.

Example 348 preparation of Compound GT-10310

The title compound GT-10310 (white solid, 22mg, yield 35％).¹H NMR(400MHz,DMSO-d6)δ12.35(s,1H),10.97(s,1H),8.38(s,1H),8.01-7.41(m,4H),7.33(s,4H),7.11-6.70(m,2H),6.17(s,1H),5.02(dd,J＝13.3,5.0Hz,1H),4.29(d,J＝16.9Hz,1H),4.16(d,J＝16.9Hz,1H),3.66-3.51(m,2H),3.39-3.21(m,3H),3.18-2.80(m,4H),2.58(d,J＝17.6Hz,1H),2.42-2.26(m,1H),2.07-1.88(m,1H),1.33-1.24(m,1H).LCMS(ESI)C₃₀H₃₀F₂N₅O₃ ⁺[M+H]⁺： calculated 546.23, found 546.3) was prepared according to the procedure of FIG. 2.

EXAMPLE 349 preparation of Compound GT-10311

The title compound GT-10311 (white solid, 12mg, yield 18％).¹H NMR(400MHz,DMSO-d6)δ12.10(s,1H),10.95(s,1H),8.32(s,1H),7.85-7.13(m,9H),6.18(s,1H),5.04(dd,J＝13.2,5.0Hz,1H),4.45(d,J＝16.8Hz,1H),4.27(d,J＝16.7Hz,1H),3.72-3.46(m,2H),3.37-3.20(m,2H),3.20-2.66(m,5H),2.66-2.53(m,2H),2.43-2.33(m,1H),2.01-1.87(m,1H).LCMS(ESI)C₃₀H₂₉F₃N₅O₃ ⁺[M+H]⁺： calculated 564.22, found 564.3) was prepared according to the procedure of FIG. 2.

EXAMPLE 350 preparation of Compound GT-10312

The title compound GT-10312 (white solid, 15mg, yield 23％).¹H NMR(400MHz,DMSO-d6)δ12.08(s,1H),10.95(s,1H),8.31(s,1H),8.01-7.12(m,9H),6.21(s,1H),5.11-4.98(m,1H),4.31(d,J＝16.8Hz,1H),4.18(d,J＝16.8Hz,1H),3.73-3.44(m,2H),3.37-3.23(m,2H),3.22-2.67(m,5H),2.66-2.53(m,2H),2.42-2.27(m,1H),2.03-1.88(m,1H).LCMS(ESI)C₃₀H₂₉F₃N₅O₃ ⁺[M+H]⁺： calculated 564.22, found 564.3) was prepared according to the procedure of FIG. 2.

EXAMPLE 351 preparation of Compound GT-10313

The title compound GT-10313 (white solid, 10mg, yield 15％).¹H NMR(400MHz,DMSO-d6)δ12.35(s,1H),10.94(s,1H),8.67-7.72(m,2H),7.69-7.11(m,6H),6.85-6.41(m,2H),6.15(s,1H),4.98(dd,J＝13.2,5.0Hz,1H),4.30(d,J＝17.2Hz,1H),4.16(d,J＝17.2Hz,1H),3.73-3.45(m,2H),3.36-3.12(m,3H),3.10-2.67(m,4H),2.65-2.52(m,2H),2.36-2.26(m,1H),1.99-1.87(m,1H).LCMS(ESI)C₃₀H₂₉F₃N₅O₃ ⁺[M+H]⁺： calculated 564.22, found 564.3) was prepared according to the procedure of FIG. 2.

EXAMPLE 352 preparation of Compound GT-10314

The target compound GT-10314 (white solid, 5mg, yield 8％).¹H NMR(400MHz,DMSO-d6)δ12.42(s,1H),11.00(s,1H),8.42(s,1H),7.53-7.02(m,9H),6.17(s,1H),5.07(dd,J＝13.2,5.1Hz,1H),4.34(d,J＝17.5Hz,1H),4.24(d,J＝17.4Hz,1H),3.58-3.51(m,2H),3.41-3.21(m,4H),3.05(s,2H),2.99-2.81(m,2H),2.62(d,J＝17.0Hz,1H),2.40-2.31(m,1H),2.07-1.95(m,1H).LCMS(ESI)C₃₀H₃₀F₂N₅O₃ ⁺[M+H]⁺： calculated 546.23, found 546 to. 3) was prepared according to the procedure of FIG. 2.

EXAMPLE 353 preparation of Compound GT-10315

The title compound GT-10315 (white solid, 16mg, yield 21％).¹H NMR(400MHz,DMSO-d6)δ11.08(s,1H),10.15(s,1H),8.43(s,1H),7.66-7.59(m,1H),7.50(d,J＝6.7Hz,1H),7.28(d,J＝7.2Hz,4H),5.06(dd,J＝12.7,5.4Hz,1H),4.31(s,2H),3.84(t,J＝5.0Hz,2H),3.68(s,2H),3.44-3.37(m,2H),3.25-3.10(m,2H),3.07-2.80(m,5H),2.68-2.53(m,2H),2.37(s,2H),2.06-1.91(m,1H).LCMS(ESI)C₂₉H₃₀F₂N₅O₅ ⁺[M+H]⁺： calculated 566.22, found 566.3) was prepared according to the procedure of scheme 1.

EXAMPLE 354 preparation of Compound GT-10316

The title compound GT-10316 (white solid, 17mg, yield 23％).¹H NMR(400MHz,DMSO-d6)δ10.96(s,1H),10.43(s,1H),7.66(s,1H),7.37(d,J＝8.2Hz,1H),7.34-7.18(m,5H),5.04(dd,J＝13.3,5.0Hz,1H),4.57-4.35(m,3H),4.26(d,J＝16.7Hz,1H),3.84(t,J＝5.3Hz,2H),3.65(s,2H),3.42-3.40(m,1H),3.15(t,J＝11.3Hz,2H),3.00-2.78(m,5H),2.69-2.53(m,2H),2.45-2.29(m,3H),2.04-1.88(m,1H).LCMS(ESI)C₂₉H₃₂F₂N₅O₄ ⁺[M+H]⁺： calculated 552.24, found 552.3) was prepared according to the procedure of scheme 1.

EXAMPLE 355 preparation of Compound GT-10317

The title compound GT-10317 (white solid, 14mg, yield 19％).¹H NMR(400MHz,DMSO-d6)δ10.95(s,1H),10.41(s,1H),7.73(s,1H),7.35-7.19(m,6H),5.03(dd,J＝13.3,5.0Hz,1H),4.38(s,2H),4.21(dd,J＝50.5,16.9Hz,2H),3.84(t,J＝5.2Hz,2H),3.65(s,2H),3.42-3.40(m,1H),3.15(s,2H),3.02-2.77(m,5H),2.68-2.52(m,2H),2.41-2.26(m,3H),2.01-1.89(m,1H).LCMS(ESI)C₂₉H₃₂F₂N₅O₄ ⁺[M+H]⁺： calculated 552.24, found 552.3) was prepared according to the procedure of scheme 1.

EXAMPLE 356 preparation of Compound GT-10318

The title compound GT-10318 (white solid, 17mg, yield 23％).¹H NMR(400MHz,DMSO-d6)δ10.94(s,1H),10.63(s,1H),8.03(s,1H),7.32-7.23(m,4H),6.65(s,1H),6.58(d,J＝12.0Hz,1H),4.98(dd,J＝13.3,5.0Hz,1H),4.40(s,2H),4.28(d,J＝17.1Hz,1H),4.14(d,J＝17.2Hz,1H),3.83(t,J＝5.3Hz,2H),3.63(s,2H),3.38(s,2H),3.16-3.03(m,2H),3.01-2.76(m,5H),2.61-2.53(m,1H),2.40-2.27(m,3H),2.01-1.84(m,1H).LCMS(ESI)C₂₉H₃₂F₂N₅O₄ ⁺[M+H]⁺： calculated 552.24, found 552.3) was prepared according to the procedure of scheme 1.

EXAMPLE 357 preparation of Compound GT-10319

The title compound GT-10319 (white solid, 21mg, yield 29％).¹H NMR(400MHz,DMSO-d6)δ11.00(s,1H),10.79(s,1H),7.32-7.18(m,6H),7.06(t,J＝8.4Hz,2H),5.08(dd,J＝13.3,5.0Hz,1H),4.48-4.34(m,2H),4.28(d,1H),4.15(d,J＝17.5Hz,1H),3.83(t,J＝5.4Hz,2H),3.62(s,2H),3.38(d,J＝12.4Hz,3H),3.18-3.07(m,2H),3.02-2.91(m,3H),2.91-2.77(m,2H),2.62(d,J＝17.0Hz,1H),2.37(s,2H),2.34-2.25(m,1H),2.05-1.95(m,1H).LCMS(ESI)C₂₉H₃₃FN₅O₄ ⁺[M+H]⁺： calculated 534.25, found 534.3) was prepared according to the procedure of scheme 1.

EXAMPLE 358 preparation of Compound GT-10320

The title compound GT-10320 (white solid, 33mg, yield 41％).¹H NMR(400MHz,DMSO-d6)611.08(s,1H),10.25(s,1H),8.44(s,1H),7.62(d,J＝10.2Hz,1H),7.50(d,J＝7.7Hz,3H),7.25(d,J＝8.0Hz,2H),5.06(dd,J＝12.8,5.4Hz,1H),4.38(s,2H),3.69(s,2H),3.44-3.36(m,2H),3.26-3.12(m,2H),3.11-2.81(m,5H),2.61-2.52(m,2H),2.23(s,2H),2.08-1.92(m,1H),1.23(s,6H).LCMS(ESI)C₃₁H₃₄ClFN₅O₅ ⁺[M+H]⁺： calculated 610.22, found 610.3) was prepared according to the procedure of scheme 1.

Example 359 preparation of Compound GT-10321

The title compound GT-10321 (white solid, 26mg, yield 33％).¹H NMR(400MHz,DMSO-d6)δ10.96(s,1H),10.44(s,1H),7.75(s,1H),7.49(d,J＝10.0Hz,2H),7.37(d,J＝8.2Hz,1H),7.25(d,J＝7.8Hz,3H),5.04(dd,J＝13.3,5.0Hz,1H),4.58_4.31(m,3H),4.26(d,J＝16.8Hz,1H),3.64(s,2H),3.36(s,2H),3.25-3.07(m,2H),3.05-2.80(m,5H),2.61-2.54(m,1H),2.44-2.30(m,1H),2.23(s,2H),2.02-1.90(m,1H),1.23(s,6H).LCMS(ESI)C₃₁H₃₆ClFN₅O₄ ⁺[M+H]⁺： calculated 596.24, found 596.3) was prepared according to the procedure of scheme 1.

EXAMPLE 360 preparation of Compound GT-10408

The title compound GT-10408 (white solid, 13mg, yield 17％).¹H NMR(400MHz,DMSO-d6)δ10.95(s,1H),10.20(s,1H),7.73(s,1H),7.50(d,J＝8.4Hz,2H),7.34(d,J＝10.7Hz,1H),7.30-7.20(m,3H),5.03(dd,J＝13.3,5.0Hz,1H),4.37(s,2H),4.22(dd,J＝50.8,16.9Hz,2H),3.67(s,2H),3.13(s,2H),3.01-2.82(m,5H),2.58(d,J＝17.6Hz,1H),2.39-2.30(m,1H),2.24(s,2H),2.02-1.87(m,1H),1.23(s,6H).LCMS(ESI)C₃₁H₃₆ClFN₅O₄ ⁺[M+H]⁺： calculated 596.24, found 596.3) was prepared according to the procedure of scheme 1.

EXAMPLE 361 preparation of Compound GT-10409

The title compound GT-10409 (white solid, 25mg, yield 32％).¹H NMR(400MHz,DMSO-d6)δ10.94(s,1H),10.52(s,1H),8.02(s,1H),7.49(d,J＝8.8Hz,2H),7.25(d,J＝8.3Hz,2H),6.74-6.50(m,2H),4.98(dd,J＝13.3,5.0Hz,1H),4.40(s,2H),4.29(d,J＝17.2Hz,1H),4.15(d,J＝17.3Hz,1H),3.65(s,2H),3.10(s,2H),2.99-2.80(m,5H),2.57(d,J＝17.3Hz,1H),2.36-2.27(m,1H),2.23(s,2H),2.00-1.86(m,1H),1.23(s,6H).LCMS(ESI)C₃₁H₃₆ClFN₅O₄ ⁺[M+H]⁺： calculated 596.24, found 596.3) was prepared according to the procedure of FIG. 1.

Example 362 preparation of Compound GT-10410

The title compound GT-10410 (white solid, 23mg, yield 30％).¹H NMR(400MHz,DMSO-d6)δ11.00(s,1H),10.67(s,1H),7.49(d,J＝8.4Hz,2H),7.30-7.13(m,4H),7.06(dd,J＝12.3,7.7Hz,2H),5.08(dd,J＝13.3,5.0Hz,1H),4.51-4.34(m,2H),4.29(d,J＝17.5Hz,1H),4.16(d,J＝17.4Hz,1H),3.64(s,2H),3.32(s,2H),3.17-3.05(m,2H),3.01-2.76(m,5H),2.63(d,J＝17.2Hz,1H),2.35-2.26(m,1H),2.21(s,2H),2.07-1.97(m,1H),1.23(s,6H).LCMS(ESI)C₃₁H₃₇ClN₅O₄ ⁺[M+H]⁺： calculated 578.25, found 578.3) was prepared according to the procedure of scheme 1.

Example 363 preparation of Compound GT-10411

The title compound GT-10411 (white solid, 18mg, yield 23％).¹H NMR(400MHz,DMSO-d6)δ11.07(s,1H),10.43(s,1H),8.44(s,1H),7.61(d,J＝8.3Hz,1H),7.50(d,J＝8.3Hz,2H),7.26-7.16(m,3H),7.02(d,J＝7.7Hz,1H),5.04(dd,J＝12.8,5.4Hz,1H),3.65(s,2H),3.49-3.38(m,3H),3.26-2.81(m,10H),2.62-2.54(m,2H),2.27-2.15(m,2H),2.03-1.93(m,1H).LCMS(ESI)C₃₀H₃₁ClF₂N₅O₄ ⁺[M+H]⁺： calculated 598.20, found 598.3) was prepared according to the procedure of scheme 1.

EXAMPLE 364 preparation of Compound GT-10412

The title compound GT-10412 (white solid, 17mg, yield 23％).¹H NMR(400MHz,DMSO-d6)δ10.93(s,1H),10.43(s,1H),7.68(s,1H),7.50(d,J＝8.4Hz,2H),7.43(d,J＝8.4Hz,1H),7.21(d,J＝8.1Hz,2H),6.89(s,1H),6.83(d,J＝8.4Hz,1H),5.08-4.92(m,1H),4.27(d,J＝16.9Hz,1H),4.16(d,J＝14.7Hz,1H),3.60(s,2H),3.47-3.39(m,3H),3.16-2.99(m,4H),2.98-2.81(m,5H),2.61-2.54(m,2H),2.37-2.26(m,1H),2.25-2.13(m,2H),2.00-1.88(m,1H).LCMS(ESI)C₃0H₃₃ClF₂N₅O₃ ⁺[M+H]⁺： calculated 584.22, found 584.3) was prepared according to the procedure of scheme 1.

EXAMPLE 365 preparation of Compound GT-10413

The title compound GT-10413 (white solid, 11mg, yield 14％).¹H NMR(400MHz,DMSO-d6)δ10.96(s,1H),10.10(s,1H),7.74(s,1H),7.51(d,J＝8.1Hz,2H),7.37(d,J＝8.2Hz,1H),7.29-7.18(m,3H),5.04(dd,J＝13.3,5.1Hz,1H),4.44(d,J＝16.8Hz,1H),4.26(d,J＝16.8Hz,1H),3.64(s,2H),3.48-3.38(m,3H),3.21-3.09(m,2H),3.08-2.84(m,7H),2.62-2.54(m,2H),2.39(dt,J＝13.3,8.7Hz,1H),2.28-2.13(m,2H),2.01-1.91(m,1H).LCMS(ESI)C₃₀H₃₂ClF₃N₅O₃ ⁺[M+H]⁺： calculated 602.21, found 602.3) was prepared according to the procedure of scheme 1.

EXAMPLE 366 preparation of Compound GT-10414

The title compound GT-10414 (white solid, 15mg, yield 20％).¹H NMR(400MHz,DMSO-d6)δ10.95(s,1H),10.27(s,1H),7.74(s,1H),7.49(d,J＝8.8Hz,2H),7.34(d,J＝10.6Hz,1H),7.23(d,J＝8.1Hz,3H),5.03(dd,J＝13.3,5.1Hz,1H),4.28(d,J＝16.9Hz,1H),4.15(d,J＝16.9Hz,1H),3.64(s,2H),3.52-3.39(m,3H),3.18(s,2H),3.06-2.85(m,6H),2.65-2.52(m,3H),2.39-2.28(m,1H),2.27-2.13(m,2H),2.01-1.88(m,1H).LCMS(ESI)C₃₀H₃₂ClF₃N₅O₃ ⁺[M+H]⁺： calculated 602.21, found 602.3) was prepared according to the procedure of scheme 1.

EXAMPLE 367 preparation of Compound GT-10415

The title compound GT-10415 (white solid, 16mg, yield 21％).¹H NMR(400MHz,DMSO-d6)δ10.94(s,1H),10.34(s,1H),8.02(s,1H),7.49(d,J＝8.8Hz,2H),7.22(d,J＝8.1Hz,2H),6.70-6.49(m,2H),4.98(dd,J＝13.3,5.0Hz,1H),4.29(d,J＝17.2Hz,1H),4.15(d,J＝17.2Hz,1H),3.60(s,2H),3.46-3.38(m,3H),3.12-2.80(m,9H),2.61-2.54(m,2H),2.36-2.18(m,3H),1.97-1.88(m,1H).LCMS(ESI)C₃₀H₃₂ClF₃N₅O₃ ⁺[M+H]⁺： calculated 602.21, found 602.3) was prepared according to the procedure of scheme 1.

EXAMPLE 368 preparation of Compound GT-10416

The title compound GT-10416 (white solid, 22mg, yield 29％).¹H NMR(400MHz,DMSO-d6)δ11.00(s,1H),10.60(s,1H),7.48(d,J＝6.9Hz,2H),7.32-7.21(m,3H),7.07(dd,J＝15.8,7.6Hz,2H),5.08(dd,J＝13.3,5.0Hz,1H),4.29(d,J＝17.5Hz,1H),4.16(d,J＝17.4Hz,1H),3.68-3.55(m,2H),3.39(s,3H),3.22-2.78(m,9H),2.63(d,J＝17.1Hz,1H),2.58-2.53(m,1H),2.39-2.28(m,1H),2.27-2.13(m,2H),2.07-1.97(m,1H).LCMS(ESI)C₃₀H₃₃ClF₂N₅O₃ ⁺[M+H]⁺： calculated 584.22, found 584.3) was prepared according to the procedure of scheme 1.

Example 369 preparation of Compound GT-10417

The title compound GT-10417 (white solid, 23mg, yield 30％).¹H NMR(400MHz,DMSO-d6)δ11.07(s,1H),10.16(s,1H),8.45(s,1H),7.61(d,J＝8.3Hz,1H),7.47(d,J＝8.3Hz,2H),7.18(d,J＝8.2Hz,3H),7.03(d,J＝7.9Hz,1H),5.04(dd,J＝12.8,5.4Hz,1H),3.60(d,J＝3.9Hz,2H),3.36(s,3H),3.19(s,3H),3.14(s,2H),3.03-2.83(m,5H),2.58(d,J＝18.0Hz,1H),2.48-2.33(m,3H),2.20(d,J＝18.1Hz,1H),2.03-1.95(m,1H),1.87-1.78(m,1H),1.70-1.61(m,1H),1.23(s,3H).LCMS(ESI)C₃₂H₃₇ClN₅O₅ ⁺[M+H]⁺： calculated 606.25, found 606.3) was prepared according to the procedure of scheme 1.

EXAMPLE 370 preparation of Compound GT-10482

The title compound GT-10482 (white solid, 10mg, yield 14％).¹H NMR(400MHz,DMSO-d6)δ10.94(s,1H),10.15(s,1H),7.82-7.54(m,1H),7.48-7.42(m,2H),7.17(d,J＝9.0Hz,2H),6.94-6.79(m,2H),5.02(dd,J＝13.2,5.0Hz,1H),4.29(d,1H),4.16(d,J＝14.6Hz,1H),3.58(d,J＝4.4Hz,2H),3.36-3.31(m,3H),3.19(s,3H),3.07(s,2H),2.99-2.84(m,4H),2.58(d,J＝19.9Hz,1H),2.48-2.30(m,4H),2.21(d,J＝18.1Hz,1H),1.98-1.78(m,2H),1.72-1.60(m,1H),1.22(s,3H).LCMS(ESI)C₃₂H₃₉ClN₅O₄ ⁺[M+H]⁺： calculated 592.27, found 592.4) was prepared according to the procedure of scheme 1.

EXAMPLE 371 preparation of Compound GT-10483

The title compound GT-10483 (white solid, 10mg, yield 13％).¹H NMR(400MHz,DMSO-d6)δ10.96(s,1H),10.01(s,1H),7.74(s,1H),7.48(d,J＝8.4Hz,2H),7.37(d,J＝8.2Hz,1H),7.26(t,J＝7.7Hz,1H),7.19(d,J＝8.3Hz,2H),5.04(dd,J＝13.3,5.1Hz,1H),4.45(d,J＝16.7Hz,1H),4.26(d,J＝16.7Hz,1H),3.58(d,J＝4.3Hz,2H),3.19(s,3H),3.17-3.06(m,2H),2.98-2.78(m,5H),2.58(d,J＝17.2Hz,1H),2.46-2.30(m,4H),2.25-2.16(m,1H),2.01-1.89(m,1H),1.90-1.77(m,1H),1.73-1.61(m,1H),1.22(s,3H).LCMS(ESI)C₃₂H₃₈ClFN₅O₄ ⁺[M+H]⁺： calculated 610.26, found 610.3) was prepared according to the procedure of FIG. 1.

EXAMPLE 372 preparation of Compound GT-10484

The title compound GT-10484 (white solid, 7mg, yield 10％).¹H NMR(400MHz,DMSO-d6)δ10.95(s,1H),9.76(s,1H),7.72(s,1H),7.47(d,J＝8.3Hz,2H),7.34(d,J＝10.7Hz,1H),7.23(d,J＝7.1Hz,1H),7.18(d,J＝8.2Hz,2H),5.03(dd,J＝13.3,5.1Hz,1H),4.28(d,J＝16.9Hz,1H),4.15(d,J＝16.9Hz,1H),3.60(s,2H),3.38(s,2H),3.18(s,3H),3.11(s,2H),3.01-2.79(m,5H),2.58(d,J＝19.2Hz,1H),2.45-2.29(m,4H),2.25-2.17(m,1H),2.00-1.90(m,1H),1.88-1.77(m,1H),1.71-1.62(m,1H),1.22(s,3H).LCMS(ESI)C₃₂H₃₈ClFN₅O₄ ⁺[M+H]⁺： calculated 610.26, found 610.4) was prepared according to the procedure of scheme 1.

EXAMPLE 373 preparation of Compound GT-10485

The title compound GT-10485 (white solid, 11mg, yield 15％).¹H NMR(400MHz,DMSO-d6)δ10.94(s,1H),10.26(s,1H),8.05(s,1H),7.46(d,J＝9.8Hz,2H),7.16(d,J＝20.3,11.1Hz,2H),6.68-6.53(m,2H),4.98(dd,J＝13.3,5.1Hz,1H),4.29(d,J＝17.2Hz,1H),4.15(d,J＝17.3Hz,1H),3.57(s,2H),3.39(s,2H),3.19(s,3H),3.10(s,2H),2.99-2.82(m,5H),2.57(d,J＝18.4Hz,1H),2.47-2.19(m,5H),1.97-1.89(m,1H),1.87-1.78(m,1H),1.70-1.60(m,1H),1.22(s,3H).LCMS(ESI)C₃₂H₃₈ClFN₅O₄ ⁺[M+H]⁺： calculated 610.26, found 610.3) was prepared according to the procedure of scheme 1.

EXAMPLE 374 preparation of Compound GT-10486

The title compound GT-10486 (white solid, 12mg, yield 16％).¹H NMR(400MHz,DMSO-d6)δ11.00(s,1H),10.18(s,1H),7.46(d,J＝8.3Hz,2H),7.28(t,J＝7.7Hz,1H),7.19(d,J＝8.3Hz,3H),7.07(dd,J＝14.2,7.7Hz,2H),5.08(dd,J＝13.3,5.0Hz,1H),4.30(d,J＝17.4Hz,1H),4.17(d,J＝17.4Hz,1H),3.62-3.48(m,3H),3.18(s,3H),3.13-2.77(m,8H),2.63(d,J＝16.9Hz,1H),2.46-2.29(m,4H),2.23-2.16(m,1H),2.04-1.96(m,1H),1.87-1.79(m,1H),1.71-1.63(m,1H),1.22(s,3H).LCMS(ESI)C₃₂H₃₉ClN₅O₄ ⁺[M+H]⁺： calculated 592.27, found 592.3) was prepared according to the procedure of scheme 1.

EXAMPLE 375 preparation of Compound GT-10487

The title compound GT-10487 (white solid, 20mg, yield 26％).¹H NMR(400MHz,DMSO-d6)δ11.00(s,1H),10.29(s,1H),7.46(d,J＝8.2Hz,2H),7.28(t,J＝7.7Hz,1H),7.23-7.12(m,3H),7.07(dd,J＝14.1,7.7Hz,2H),5.08(dd,J＝13.3,5.0Hz,1H),4.30(d,J＝17.5Hz,1H),4.17(d,J＝17.4Hz,1H),3.58(s,2H),3.32-3.26(m,2H),3.17-3.03(m,2H),2.98-2.81(m,4H),2.63(d,J＝17.5Hz,1H),2.55-2.52(m,1H),2.41-2.26(m,3H),2.02(s,3H),1.48(t,J＝6.2Hz,2H),0.97(s,6H).LCMS(ESI)C₃₂H₃₉ClN₅O₃ ⁺[M+H]⁺： calculated 576.27, found 576.3) was prepared according to the method of scheme 1.

EXAMPLE 376 preparation of Compound GT-10488

The title compound GT-10488 (white solid, 14mg, yield 18％).¹H NMR(400MHz,DMSO-d6)δ11.00(s,1H),10.28(s,1H),7.31-7.15(m,6H),7.06(t,J＝7.8Hz,2H),5.08(dd,J＝13.3,5.0Hz,1H),4.29(d,J＝17.4Hz,1H),4.16(d,J＝17.4Hz,1H),3.57(s,2H),3.33-3.29(m,2H),3.16-3.02(m,2H),3.00-2.75(m,5H),2.62(d,J＝16.8Hz,1H),2.39-2.24(m,3H),2.09-1.96(m,3H),1.48(t,J＝6.2Hz,2H),0.97(s,6H).LCMS(ESI)C₃₂H₃₉FN₅O₃ ⁺[M+H]⁺： calculated 560.30, found 560.4) was prepared according to the procedure of scheme 1.

Example 377 preparation of Compound GT-10489

The title compound GT-10489 (white solid, 22mg, yield 31％).¹H NMR(400MHz,DMSO-d6)δ10.97(s,1H),7.40(d,J＝8.5Hz,2H),7.29-7.22(m,3H),7.01(dd,J＝10.3,7.7Hz,2H),6.92-6.41(m,1H),5.06(dd,J＝13.3,5.1Hz,1H),4.24(dd,J＝39.2,17.5Hz,2H),3.41-3.30(m,2H),2.96-2.87(m,1H),2.69-2.53(m,3H),2.44-2.27(m,4H),2.23-1.82(m,4H),1.56-1.36(m,2H),0.98(d,J＝9.3Hz,6H).LCMS(ESI)C₃₂H₃₇ClN₅O₄ ⁺[M+H]⁺： calculated 590.25, found 590.3) was prepared according to the procedure of scheme 3.

EXAMPLE 378 preparation of Compound GT-10490

The title compound GT-10490 (white solid, 25mg, yield 34％).¹H NMR(400MHz,DMSO-d6)δ10.97(s,1H),7.30-7.21(m,3H),7.16(t,J＝8.8Hz,2H),7.00(dd,J＝14.6,7.7Hz,2H),6.79(s,1H),5.06(dd,J＝13.3,5.0Hz,1H),4.24(dd,J＝39.9,17.5Hz,2H),3.43-3.00(m,5H),2.95-2.85(m,1H),2.60(d,J＝17.4Hz,2H),2.35(d,J＝16.9Hz,4H),2.19-1.82(m,4H),1.54-1.37(m,2H),0.99(d,J＝11.8Hz,6H).LCMS(ESI)C₃₂H₃₇FN₅O₄ ⁺[M+H]⁺： calculated 574.28, found 574.3) was prepared according to the procedure of FIG. 3.

EXAMPLE 379 preparation of Compound GT-10491

The title compound GT-10491 (white solid, 9mg, yield 13％).¹H NMR(400MHz,DMSO-d6)δ10.95(s,1H),7.58-7.50(m,1H),7.47-7.36(m,3H),7.24(d,J＝9.2Hz,2H),7.12-7.03(m,2H),5.04(dd,J＝13.3,5.0Hz,1H),4.33(d,1H),4.21(d,J＝16.8,6.8Hz,1H),3.43(s,5H),3.03(s,4H),2.95-2.85(m,1H),2.62-2.54(m,1H),2.49-2.28(m,5H),2.18(s,2H),1.99-1.90(m,1H),1.48-1.41(m,2H),1.00-0.92(m,6H).LCMS(ESI)C₃₂H₃₉ClN₅O₃ ⁺[M+H]⁺： calculated 574.27, found 574.3) was prepared according to the procedure of FIG. 1.

EXAMPLE 380 preparation of Compound GT-10492

The title compound GT-10492 (white solid, 30mg, yield 38％).¹H NMR(400MHz,DMSO-d6)δ11.08(s,1H),10.34(s,1H),8.46(s,1H),7.62(d,J＝10.3Hz,1H),7.50(d,J＝8.2Hz,3H),7.22(d,J＝8.1Hz,2H),5.06(dd,J＝12.8,5.4Hz,1H),3.74(d,J＝65.7Hz,2H),3.54-3.37(m,3H),3.30-3.17(m,2H),3.09-2.94(m,5H),2.93-2.73(m,2H),2.61-2.52(m,2H),2.50(s,1H),2.27-2.15(m,2H),2.06-1.93(m,1H).LCMS(ESI)C₃₀H₃₀ClF₃N₅O₄ ⁺[M+H]⁺： calculated 616.19, found 616.2) was prepared according to the procedure of scheme 1.

Example 381 preparation of Compound GT-10493

The title compound GT-10493 (white solid, 21mg, yield 27％).¹H NMR(400MHz,DMSO-d6)δ11.08(s,1H),9.82(s,1H),8.43(s,1H),7.63(d,J＝10.2Hz,1H),7.56-7.40(m,3H),7.18(d,J＝7.0Hz,2H),5.06(dd,J＝12.6,5.2Hz,1H),3.62(s,2H),3.37(s,2H),3.25-3.13(m,5H),3.10-2.83(m,5H),2.67-2.54(m,2H),2.45-2.29(m,3H),2.26-2.14(m,1H),2.07-1.95(m,1H),1.91-1.78(m,1H),1.73-1.62(m,1H),1.23(s,3H).LCMS(ESI)C₃₂H₃₆ClFN₅O₅ ⁺[M+H]⁺： calculated 624.24, found 624.3) was prepared according to the method of scheme 1.

EXAMPLE 382 preparation of Compound GT-10494

The title compound GT-10494 (white solid, 6mg, yield 8％).¹H NMR(400MHz,DMSO-d6)δ12.80(s,1H),11.06(s,1H),8.79(d,J＝5.7Hz,1H),8.63-7.75(m,4H),7.60(d,J＝8.0Hz,1H),7.57-7.28(m,4H),7.21(s,1H),7.03(s,1H),5.04(dd,J＝12.8,5.4Hz,1H),3.65(s,2H),3.35-3.22(m,3H),3.05(s,3H),2.95-2.81(m,2H),2.64-2.55(m,2H),2.06-1.89(m,1H).LCMS(ESI)C₂₉H₂₉N₆O₄ ⁺[M+H]⁺： calculated 525.22, found 525.3) was prepared according to the procedure of scheme 2.

EXAMPLE 383 preparation of Compound GT-10495

The title compound GT-10495 (white solid, 7mg, yield 9％).¹H NMR(400MHz,DMSO-d6)δ13.50-11.94(m,1H),11.08(s,1H),8.81(d,J＝5.9Hz,2H),8.20(s,2H),8.00-7.65(m,2H),7.63(d,J＝10.2Hz,1H),7.59-7.20(m,5H),5.06(dd,J＝12.7,5.4Hz,1H),3.70(s,2H),3.32-3.22(m,2H),3.03(s,4H),2.94-2.81(m,2H),2.58(d,J＝19.5Hz,2H),2.05-1.96(m,1H).LCMS(ESI)C₂₉H₂₈FN₆O₄ ⁺[M+H]⁺： calculated 543.22, found 543.3) was prepared according to the procedure of FIG. 2.

EXAMPLE 384 preparation of Compound GT-10509

The title compound GT-10509 (white solid, 23mg, yield 32％).¹H NMR(400MHz,DMSO-d6)δ11.07(s,1H),8.74-8.67(m,2H),8.04-7.90(m,2H),7.78(d,J＝7.9Hz,2H),7.62(d,J＝8.3Hz,1H),7.55-7.40(m,2H),7.25(s,1H),7.08(d,J＝8.1Hz,1H),6.08(s,1H),5.09-5.02(m,1H),4.39(s,2H),3.36(s,3H),3.14(s,4H),2.93-2.81(m,1H),2.58(d,J＝17.8Hz,1H),2.09-1.94(m,1H).LCMS(ESI)C₂₈H₂₈N₇O₄ ⁺[M+H]⁺： calculated 526.22, found 526.3) was prepared according to the procedure of scheme 2.

Example 385 preparation of Compound GT-10510

The target compound GT-10510 (white solid, 36mg, yield 49％).¹H NMR(400MHz,DMSO-d6)611.09(s,1H),8.71(d,J＝4.1Hz,2H),8.49(s,1H),8.00-7.88(m,2H),7.77(d,J＝7.9Hz,2H),7.65(d,J＝10.3Hz,1H),7.55(d,J＝7.0Hz,1H),7.51-7.42(m,2H),6.05(s,1H),5.07(dd,J＝12.8,5.4Hz,1H),3.26(d,J＝56.4Hz,9H),2.93-2.83(m,1H),2.55(d,J＝9.1Hz,1H),2.07-1.96(m,1H).LCMS(ESI)C₂₈H₂₇FN₇O₄ ⁺[M+H]⁺： calculated 544.21, found 544 to.3) was prepared according to the procedure of FIG. 2.

Example 386 preparation of Compound GT-10511

The title compound GT-10511 (white solid, 26mg, yield 37％).¹H NMR(400MHz,DMSO-d6)δ10.95(s,1H),8.69(d,J＝8.9Hz,2H),7.99-7.91(m,2H),7.76(d,J＝7.9Hz,2H),7.49-7.39(m,3H),6.95(s,1H),6.89(d,J＝8.3Hz,1H),6.07(s,1H),5.02(dd,J＝13.1,4.9Hz,1H),4.29(d,J＝17.0Hz,1H),4.16(d,J＝17.0Hz,1H),3.33(s,4H),3.10(s,4H),2.94-2.84(m,1H),2.58(d,J＝16.8Hz,1H),2.41-2.28(m,1H),1.99-1.90(m,1H).LCMS(ESI)C₂₈H₃₀N₇O₃ ⁺[M+H]⁺： calculated 512.24, found 512.3) was prepared according to the procedure of FIG. 2.

EXAMPLE 387 preparation of Compound GT-10512

The title compound GT-10512 (white solid, 10mg, yield 14％).¹H NMR(400MHz,DMSO-d6)δ10.96(s,1H),8.76-8.65(m,2H),7.99-7.92(m,2H),7.76(d,J＝7.8Hz,2H),7.52-7.46(m,2H),7.41(d,J＝8.2Hz,1H),7.29(t,J＝7.7Hz,1H),6.06(s,1H),5.04(dd,J＝13.3,5.0Hz,1H),4.44(d,1H),4.28(d,1H),3.32(s,4H),3.14(s,4H),2.96-2.85(m,1H),2.56(d,1H),2.47-2.32(m,1H),2.01-1.90(m,1H).LCMS(ESI)C₂₈H₂₉FN₇O₃ ⁺[M+H]⁺： calculated 530.23, found 530.3) was prepared according to the procedure of FIG. 2.

EXAMPLE 388 preparation of Compound GT-10513

The title compound GT-10513 (white solid, 16mg, yield 23％).¹H NMR(400MHz,DMSO-d6)δ10.95(s,1H),8.71(d,J＝4.8Hz,2H),7.94(t,J＝8.0Hz,2H),7.76(d,J＝9.1Hz,3H),7.52-7.43(m,2H),7.37(d,J＝8.7Hz,1H),7.26(d,J＝7.1Hz,1H),6.04(s,1H),5.04(dd,J＝13.3,5.0Hz,1H),4.31(d,J＝17.0Hz,1H),4.18(d,J＝16.9Hz,1H),3.31(s,4H),3.14(s,4H),2.97-2.87(m,1H),2.59(d,J＝17.2Hz,1H),2.41-2.30(m,1H),2.00-1.90(m,1H).LCMS(ESI)C₂₈H₂₉FN₇O₃ ⁺[M+H]⁺： calculated 530.23, found 530.3) was prepared according to the procedure of FIG. 2.

Example 389 preparation of Compound GT-10514

The title compound GT-10514 (white solid, 20mg, yield 28％).¹H NMR(400MHz,DMSO-d6)δ10.95(s,1H),8.72-8.67(m,2H),7.98-7.93(m,2H),7.79(d,J＝7.8Hz,2H),7.48(dd,J＝7.6,4.9Hz,2H),6.75-6.60(m,2H),6.08(s,1H),4.98(dd,J＝13.3,5.0Hz,1H),4.31(d,1H),4.18(d,J＝6.0Hz,1H),3.34(s,4H),3.11(s,4H),2.96-2.84(m,1H),2.58(d,J＝17.3Hz,1H),2.35-2.23(m,1H),2.00-1.89(m,1H).LCMS(ESI)C₂₈H₂₉FN₇O₃ ⁺[M+H]⁺： calculated 530.23, found 530.3) was prepared according to the procedure of FIG. 2.

EXAMPLE 390 preparation of Compound GT-10515

The title compound GT-10515 (white solid, 15mg, yield 22％).¹H NMR(400MHz,DMSO-d6)δ11.01(s,1H),8.70(d,J＝4.1Hz,2H),8.03-7.91(m,2H),7.77(d,J＝7.8Hz,2H),7.47(dd,J＝6.8,4.9Hz,2H),7.28(t,J＝7.7Hz,1H),7.07(dd,J＝13.1,7.6Hz,2H),6.13(s,1H),5.10(dd,J＝13.3,5.0Hz,1H),4.36(d,1H),4.27(d,1H),3.32(s,4H),3.11(s,4H),2.99-2.87(m,1H),2.64(d,J＝17.5Hz,2H),2.43-2.34(m,1H),2.10-1.99(m,1H).LCMS(ESI)C₂₈H₃₀N₇O₃ ⁺[M+H]⁺： calculated 512.24, found 512.3) was prepared according to the procedure of FIG. 2.

Example 391 preparation of Compound GT-10615

The title compound GT-10615 (white solid, 7mg, yield 10％).¹H NMR(400MHz,DMSO-d6)δ12.49(s,1H),10.93(s,1H),7.75(d,J＝7.3Hz,4H),7.47-7.37(m,6H),6.99-6.74(m,2H),5.89(d,J＝10.4Hz,1H),5.02(dd,J＝13.2,5.1Hz,1H),4.29(d,1H),4.15(d,J＝16.8Hz,1H),3.82(d,J＝22.0Hz,4H),3.40-3.23(m,4H),2.93-2.85(m,1H),2.71-2.54(m,3H),2.37-2.31(m,1H),2.14-1.75(m,4H).LCMS(ESI)C₃₃H₃₆N₅O₃ ⁺[M+H]⁺： calculated 550.28, found 550.3) was prepared according to the procedure of scheme 2.

EXAMPLE 392 preparation of Compound GT-10616

The title compound GT-10616 (yellow solid, 7mg, yield 10％).¹H NMR(400MHz,DMSO-d6)δ12.79(s,1H),10.93(s,2H),7.99-7.94(m,2H),7.50-7.45(m,3H),7.33-7.29(m,4H),6.93-6.86(m,1H),6.48-6.40(m,1H),5.02(dd,J＝13.2,5.1Hz,2H),4.28(d,J＝9.4Hz,1H),4.18(d,1H),3.94(s,5H),3.34-3.26(m,2H),2.92-2.86(m,2H),2.58(d,J＝16.1Hz,2H),2.35-2.30(m,2H),1.95(s,3H).LCMS(ESI)C₃₃H₃₄F₂N₅O₃ ⁺[M+H]⁺： calculated 586.26, found 586.3) was prepared according to the procedure of scheme 2.

Example 393 preparation of Compound GT-10617

The title compound GT-10617 (yellow solid, 10mg, yield 14％).¹H NMR(400MHz,DMSO-d6)δ12.87(s,1H),10.93(s,2H),7.75(d,J＝9.9Hz,2H),7.62(d,J＝8.0Hz,2H),7.54-7.48(m,3H),7.25(t,J＝7.5Hz,3H),6.86(s,1H),6.13-5.92(m,1H),5.09-4.91(m,2H),4.30(d,J＝8.1Hz,1H),4.19(d,J＝8.4Hz,1H),3.91-3.78(m,4H),3.38-3.30(m,3H),2.94-2.87(m,2H),2.56(s,2H),2.37-2.30(m,2H),1.97-1.90(m,3H).LCMS(ESI)C₃₃H₃₄F₂N₅O₃ ⁺[M+H]⁺： calculated 586.26, found 586.3) was prepared according to the procedure of scheme 2.

Example 394 preparation of Compound GT-10618

The title compound GT-10618 (white solid, 5mg, yield 7％).¹H NMR(400MHz,DMSO-d6)δ12.70(s,1H),10.93(s,1H),7.87-7.76(m,4H),7.43(d,J＝8.4Hz,1H),7.29(t,J＝8.7Hz,4H),6.97-6.81(m,2H),5.95(d,J＝10.4Hz,1H),5.02(dd,J＝13.1,4.9Hz,1H),4.29(d,J＝16.8Hz,1H),4.15(d,J＝16.8Hz,1H),3.81(s,4H),3.72-3.61(m,2H),3.39-3.28(m,2H),2.93-2.85(m,1H),2.75-2.56(m,3H),2.39-2.27(m,2H),2.00-1.86(m,3H).LCMS(ESI)C₃₃H₃₄F₂N₅O₃ ⁺[M+H]⁺： calculated 586.26, found 586.3) was prepared according to the procedure of scheme 2.

EXAMPLE 395 preparation of Compound GT-10619

The title compound GT-10619 (yellow solid, 14mg, yield 18％).¹H NMR(400MHz,DMSO-d6)δ12.85(s,1H),10.93(s,1H),7.79(d,J＝7.9Hz,4H),7.52(d,J＝7.4Hz,5H),7.44(d,J＝8.1Hz,1H),6.98-6.86(m,2H),5.99(d,J＝10.0Hz,1H),5.06-5.01(m,1H),4.30(d,1H),4.16(d,J＝16.8Hz,1H),3.84(s,5H),3.46-3.33(m,2H),2.94-2.86(m,2H),2.56(d,2H),2.38-2.29(m,2H),1.94(s,4H).LCMS(ESI)C₃₃H₃₄Cl₂N₅O₃ ⁺[M+H]⁺： calculated 618.20, found 618.3) was prepared according to the procedure of scheme 2.

EXAMPLE 396 preparation of Compound GT-10620

The title compound GT-10620 (red solid, 26mg, yield 36％).¹H NMR(400MHz,DMSO-d6)δ11.85(s,1H),10.95(s,1H),8.69(d,J＝8.3Hz,1H),7.89(t,J＝7.7,1.7Hz,1H),7.64(d,J＝6.4Hz,2H),7.57-7.50(m,2H),7.47-7.42(m,4H),7.28-7.15(m,2H),6.16(s,1H),5.05(dd,J＝13.3,5.0Hz,1H),4.05-3.81(m,6H),3.29-3.01(m,3H),3.00-2.84(m,2H),2.59(d,J＝17.5Hz,1H),2.39-2.33(m,1H),2.27-2.05(m,3H),2.03-1.82(m,2H).LCMS(ESI)C₃₂H₃₅N₆O₃ ⁺[M+H]⁺： calculated 551.28, found 551.3) was prepared according to the procedure of scheme 2.

EXAMPLE 397 preparation of Compound GT-10621

The title compound GT-10621 (red solid, 8mg, yield 12％).¹H NMR(400MHz,DMSO-d6)δ10.94(s,2H),8.67-8.63(m,2H),7.96-7.90(m,2H),7.70(d,2H),7.52-7.42(m,4H),7.12-6.99(m,2H),5.95(s,1H),5.04(dd,J＝13.3,5.0Hz,2H),4.33(d,2H),4.19(d,2H),3.10(s,1H),2.94-2.86(m,3H),2.59(d,J＝16.3Hz,2H),2.40-2.33(m,2H),1.99-1.83(m,5H).LCMS(ESI)C₃₂H₃₅N₆O₃ ⁺[M+H]⁺： calculated 551.28, found 551.3) was prepared according to the procedure of scheme 2.

Example 398 preparation of Compound GT-10622

The title compound GT-10622 (yellow solid, 10mg, yield 14％).¹H NMR(400MHz,DMSO-d6)δ13.18(s,1H),10.94(s,1H),9.16(s,1H),8.77(d,J＝4.1Hz,1H),8.66(d,J＝8.0Hz,1H),7.97-7.80(m,3H),7.51-7.40(m,4H),7.09-6.77(m,2H),6.20(s,1H),5.03(dd,J＝13.1,5.1Hz,1H),4.31(d,1H),4.17(d,J＝15.6Hz,1H),3.66-3.50(m,2H),3.37(d,1H),3.19-3.04(m,1H),2.91-2.88(m,2H),2.85-2.67(m,3H),2.58(d,J＝17.8Hz,2H),2.37-2.31(m,1H),2.24-1.89(m,4H).LCMS(ESI)C₃₁H₃₄N₇O₃ ⁺[M+H]⁺： calculated 552.27, found 552.3) was prepared according to the procedure of scheme 2.

EXAMPLE 399 preparation of Compound GT-09104

The title compound GT-09104 (white solid, 17mg, yield 21％).¹H NMR(400MHz,DMSO)δ10.94(s,2H),8.77(s,2H),7.65(s,1H),7.46(d,J＝8.3Hz,1H),6.94(s,1H),6.88(d,J＝8.4Hz,1H),5.03(dd,J＝13.3,5.1Hz,1H),4.24(dd,J＝53.7,16.9Hz,2H),3.49(d,J＝11.7Hz,2H),3.25-3.14(m,2H),3.05(s,6H),2.95-2.87(m,1H),2.82(s,2H),2.59(d,J＝17.4Hz,1H),2.41-2.28(m,1H),2.11(s,3H),1.97-1.92(m,1H),1.88(s,6H),1.78-1.54(m,10H),1.33(s,6H).LCMS(ESI)C₃₄H₅₁N₆O₃ ⁺[M+H]⁺： calculated 591.40, found 591.4) was prepared according to the method of scheme 2.

EXAMPLE 400 preparation of Compound GT-09105

The title compound GT-09105 (white solid, 7mg, yield 9％).¹H NMR(400MHz,DMSO)δ10.96(s,1H),10.67(s,1H),8.76(s,2H),7.78(s,1H),7.42(d,J＝8.2Hz,1H),7.31(t,J＝7.7Hz,1H),5.04(dd,J＝13.3,5.1Hz,1H),4.46(d,J＝16.8Hz,1H),4.28(d,J＝16.7Hz,1H),3.51(d,J＝10.2Hz,2H),3.28-3.14(m,3H),3.13-3.04(m,5H),2.93-2.77(m,3H),2.59(d,J＝17.0Hz,1H),2.45-2.34(m,1H),2.11(s,3H),1.99-1.93(m,1H),1.88(s,6H),1.71(d,J＝11.1Hz,2H),1.70-1.57(m,8H),1.33(s,6H).LCMS(ESI)C₃₄H₅₀FN₆O₃ ⁺[M+H]⁺： calculated 609.39, found 609.5) was prepared according to the method of FIG. 2.

EXAMPLE 401 preparation of Compound GT-09106

The title compound GT-09106 (white solid, 20mg, yield 25％).¹H NMR(400MHz,DMSO)δ10.96(s,1H),10.69(s,1H),8.80(s,2H),7.78(s,1H),7.36(d,J＝10.6Hz,1H),7.28(d,J＝7.1Hz,1H),5.05(dd,J＝13.2,5.0Hz,1H),4.32(d,J＝17.0Hz,1H),4.19(d,J＝16.8Hz,1H),3.50(d,J＝9.2Hz,2H),3.28-3.14(m,3H),3.13-3.01(m,5H),2.95-2.86(m,1H),2.86-2.76(m,2H),2.59(d,J＝17.5Hz,1H),2.41-2.29(m,1H),2.11(s,3H),1.99-1.93(m,1H),1.88(s,6H),1.72(s,2H),1.69-1.55(m,8H),1.33(s,6H).LCMS(ESI)C₃₄H₅₀FN₆O₃ ⁺[M+H]⁺： calculated 609.39, found 609.5) was prepared according to the method of FIG. 2.

EXAMPLE 402 preparation of Compound GT-09107

The title compound GT-09107 (white solid, 19mg, yield 23％).¹H NMR(400MHz,DMSO)δ10.95(s,2H),8.77(s,2H),8.13(s,1H),6.70(s,1H),6.62(d,J＝12.4Hz,1H),4.99(dd,J＝13.3,5.1Hz,1H),4.31(d,J＝17.3Hz,1H),4.17(d,J＝17.3Hz,1H),3.47(d,2H),3.21(s,3H),3.07(s,7H),3.00-2.74(m,4H),2.58(d,J＝16.8Hz,1H),2.37-2.27(m,1H),2.11(s,3H),1.97-1.89(m,2H),1.73(s,2H),1.71-1.54(m,10H),1.33(s,6H).LCMS(ESI)C₃₄H₅₀FN₆O₃ ⁺[M+H]⁺： calculated 609.39, found 609.4) was prepared according to the method of scheme 2.

EXAMPLE 403 preparation of Compound GT-09108

The title compound GT-09108 (white solid, 23mg, yield 29％).¹H NMR(400MHz,DMSO)δ11.00(s,1H),10.97(s,1H),8.76(s,2H),7.29(d,J＝7.7Hz,1H),7.12-7.00(m,2H),5.10(dd,J＝13.3,5.0Hz,1H),4.36(d,J＝17.5Hz,1H),4.23(d,J＝17.5Hz,1H),3.50(s,2H),3.24-3.10(m,3H),3.10-3.02(m,5H),2.97-2.88(m,1H),2.81(s,2H),2.62(d,J＝17.1Hz,1H),2.44-2.31(m,1H),2.09(d,J＝19.4Hz,3H),2.06-1.97(m,1H),1.88(s,6H),1.74(s,2H),1.69-1.57(m,8H),1.33(s,6H).LCMS(ESI)C₃₄H₅₁N₆O₃ ⁺[M+H]⁺： calculated 591.40, found 591.4) was prepared according to the method of scheme 2.

EXAMPLE 404 preparation of Compound GT-09109

The title compound GT-09109 (white solid, 20mg, yield 24％).¹H NMR(400MHz,DMSO)δ10.94(s,1H),10.87(s,1H),8.79(s,2H),7.44(d,J＝8.4Hz,1H),7.07-6.85(m,2H),5.03(dd,J＝13.2,5.0Hz,1H),4.31(d,J＝16.8Hz,1H),4.18(d,J＝16.8Hz,1H),3.77(s,2H),3.36(s,1H),3.20(d,J＝4.9Hz,1H),3.06(s,1H),3.01-2.73(m,8H),2.70-2.53(m,3H),2.39-2.26(m,1H),2.11(s,3H),2.00-1.93(m,1H),1.89(s,6H),1.76-1.54(m,10H),1.34(s,6H).LCMS(ESI)C₃₆H₅₃N₆O₃ ⁺[M+H]⁺： calculated 617.42, found 617.5) was prepared according to the method of scheme 2.

EXAMPLE 405 preparation of Compound GT-09110

The title compound GT-09110 (white solid, 24mg, yield 29％).¹H NMR(400MHz,DMSO)δ10.94(s,1H),10.75(s,1H),8.79(s,2H),7.63(s,1H),7.46(d,J＝8.3Hz,1H),6.97(s,1H),6.90(d,J＝8.8Hz,1H),5.03(dd,J＝13.2,5.0Hz,1H),4.31(d,J＝16.9Hz,1H),4.18(d,J＝16.9Hz,1H),4.04(s,1H),3.26(d,J＝11.4Hz,2H),2.97-2.91(m,4H),2.82(s,3H),2.59(d,J＝16.4Hz,1H),2.35-2.28(m,1H),2.18(s,4H),2.11(s,4H),1.99-1.94(m,1H),1.89(s,6H),1.77(s,2H),1.67-1.58(m,8H),1.34(s,6H).LCMS(ESI)C₃₆H₅₃N₆O₃ ⁺[M+H]⁺： calculated 617.42, found 617.5) was prepared according to the method of scheme 2.

EXAMPLE 406 preparation of Compound GT-09111

The title compound GT-09111 (white solid, 13mg, yield 16％).¹H NMR(400MHz,DMSO)δ11.29(s,1H),10.94(s,1H),8.81(s,2H),7.47(d,J＝8.3Hz,1H),7.11-6.91(m,2H),5.03(dd,J＝13.2,5.1Hz,1H),4.32(d,1H),4.18(d,J＝17.0Hz,1H),3.90(s,2H),3.84-3.78(m,4H),3.13(d,J＝7.7Hz,2H),2.93-2.84(m,2H),2.81(s,3H),2.59(d,J＝17.0Hz,2H),2.38-2.31(m,1H),2.11(s,3H),1.97-1.93(m,2H),1.89(s,6H),1.70-1.54(m,10H),1.52(s,2H),1.31(s,6H).LCMS(ESI)C₃₇H₅₅N₆O₃ ⁺[M+H]⁺： calculated 631.43, found 631.5) was prepared according to the method of scheme 2.

EXAMPLE 407 preparation of Compound GT-09112

The title compound GT-09112 (white solid, 17mg, yield 21％).¹H NMR(400MHz,DMSO)δ10.94(s,1H),10.85(s,1H),8.74(s,2H),7.70(s,1H),7.45(d,J＝8.4Hz,1H),6.96(s,1H),6.88(d,J＝8.2Hz,1H),5.03(dd,J＝13.2,5.1Hz,1H),4.30(d,J＝16.7Hz,1H),4.17(d,J＝16.9Hz,1H),3.54(s,2H),3.28(d,J＝13.5Hz,4H),3.15-3.06(m,3H),3.03-2.73(m,5H),2.58(d,J＝17.6Hz,1H),2.38-2.28(m,1H),2.11(s,3H),2.04(s,1H),1.98-1.92(m,1H),1.88(s,6H),1.73(s,2H),1.68-1.55(m,8H),1.33(s,6H).LCMS(ESI)C₃₅H₅₃N₆O₃ ⁺[M+H]⁺： calculated 605.42, found 605.5) was prepared according to the method of scheme 2.

EXAMPLE 408 preparation of Compound GT-09113

The title compound GT-09113 (white solid, 15mg, yield 19％).¹H NMR(400MHz,DMSO)δ10.95(s,1H),9.57(s,1H),9.00-8.58(m,3H),7.49-7.35(m,1H),7.11-6.78(m,2H),5.04(d,1H),4.38-4.17(m,3H),2.99-2.89(m,2H),2.87-2.75(m,4H),2.58(d,J＝16.6Hz,1H),2.34(d,J＝10.4Hz,1H),2.10(s,3H),1.98-1.93(m,1H),1.88(s,8H),1.69-1.56(m,12H),1.34(d,J＝6.8Hz,8H).LCMS(ESI)C₃₅H₅₁N₆O₃ ⁺[M+H]⁺： calculated 603.40, found 603.5) was prepared according to the method of scheme 2.

EXAMPLE 409 preparation of Compound GT-09114

The title compound GT-09114 (white solid, 22mg, yield 27％).¹H NMR(400MHz,DMSO)δ11.25(s,1H),10.94(s,1H),8.79(s,2H),8.14(s,1H),7.45(dd,J＝8.3,3.6Hz,1H),7.04-6.81(m,2H),5.03(dd,J＝13.2,5.0Hz,1H),4.24(dd,J＝53.9,16.8Hz,3H),3.53-3.42(m,2H),3.23-2.99(m,3H),2.96-2.72(m,4H),2.59(d,J＝16.6Hz,1H),2.44-2.26(m,2H),2.19(s,1H),2.11(s,3H),1.98-1.92(m,1H),1.89(s,6H),1.72(s,1H),1.72-1.55(m,10H),1.35(s,6H).LCMS(ESI)C₃₅H₅₁N₆O₃ ⁺[M+H]⁺： calculated 603.40, found 603.5) was prepared according to the method of scheme 2.

EXAMPLE 410 preparation of Compound GT-09115

The title compound GT-09115 (white solid, 22mg, yield 27％).¹H NMR(400MHz,DMSO)δ10.95(d,J＝7.5Hz,1H),10.15(s,1H),8.75(s,2H),7.45(d,J＝8.4Hz,1H),7.10(s,1H),7.05(d,J＝5.8Hz,1H),5.03(dd,J＝13.3,5.0Hz,1H),4.30(d,J＝16.8Hz,1H),4.17(d,J＝16.9Hz,1H),3.46-3.22(m,7H),3.03(s,1H),2.91-2.76(m,3H),2.59(d,J＝17.1Hz,1H),2.40-2.33(m,1H),2.17(s,3H),2.11(s,4H),1.98-1.92(m,1H),1.88(s,6H),1.75(s,2H),1.69-1.57(m,8H),1.31(d,J＝17.3Hz,6H).LCMS(ESI)C₃₆H₅₃N₆O₃ ⁺[M+H]⁺： calculated 617.42, found 617.5) was prepared according to the method of scheme 2.

Example 411 preparation of Compound GT-09116

The title compound GT-09116 (yellow solid, 30mg, yield 36.28％).¹H NMR(400MHz,DMSO)δ11.07(s,1H),10.98(s,1H),8.75(s,2H),8.57(d,J＝46.0Hz,1H),7.64(d,J＝8.3Hz,1H),7.24(s,1H),7.06(s,1H),5.05(dd,J＝12.8,5.4Hz,1H),3.51(d,J＝10.3Hz,2H),3.25(s,2H),3.09(s,6H),2.88-2.75(m,3H),2.56(d,1H),2.11(s,3H),2.04-1.97(m,1H),1.88(s,6H),1.74(s,2H),1.63(dd,J＝29.4,12.4Hz,9H),1.33(s,6H).LCMS(ESI)C₃₄H₄9N₆O₄ ⁺[M+H]⁺： calculated 605.38, found 605.4) was prepared according to the method of scheme 2.

Example 412 preparation of Compound GT-09117

The target compound GT-09117 (yellow solid, 23mg, yield 28％).¹H NMR(400MHz,DMSO)δ11.09(s,1H),10.81(s,1H),8.81(s,2H),8.50(s,1H),7.64(d,J＝10.2Hz,1H),7.56(d,J＝7.0Hz,1H),5.07(dd,J＝12.8,5.4Hz,1H),3.51(d,J＝10.0Hz,2H),3.283.15(m,4H),3.09(d,J＝10.1Hz,4H),2.92-2.78(m,3H),2.59(d,J＝18.6Hz,1H),2.11(s,3H),2.06-1.98(m,1H),1.88(d,J＝7.8Hz,6H),1.73(s,2H),1.69-1.56(m,9H),1.33(s,6H).LCMS(ESI)C₃₄H₄₈FN₆O₄ ⁺[M+H]⁺： calculated 623.37, found 623.4. Biological Activity assay) was prepared according to the method of Synthesis scheme 2

Experimental reagents and materials: reagent and material suppliers or sources of human multiple myeloma cells: MM.1S ATCC (AMERICAN TYPE CultureCollection) human B lymphomatoid cells: RPMI-8226 ATCC human diffuse large B lymphomatoid cells: TMD8 Kang Yuanbo biological technology (Beijing) Limited human myelomonocytic leukemia cells: MV-4-11 ATCC human small cell lung cancer cells: H196 ATCC human pancreatic cancer cells: CFPAC-1 Dalian Mey Biotechnology Limited human malignant melanoma cells: A375 Dalian Mey Biotechnology Limited RPMI-1640 medium ATCCIMDM medium Gibco DMEM high sugar medium Dalian Mey Biotechnology Limited cell viability detection kit Dalian Mey Biotechnology Limited bovine serum (FBS) Sunrise Science Products Penicillin-Streptomycin (Penicillin and streptomycin) Beijing full gold technology Limited full gold animal technology Limited Beijing full gold gene detection kit and applied biological technology

The experimental method comprises the following steps:

Cell culture

Tumor cells used in the present disclosure were cultured in the cell culture medium of table a in 37 ℃ incubator containing 5% co ₂, respectively. All cells were identified as correct by STR and were mycoplasma negative by mycoplasma detection kit prior to the experiment. Table a tumor cells and cell culture media used in the present disclosure

I. Half maximal inhibitory concentration (IC ₅₀) assay of compounds of the present disclosure on tumor cells

IC ₅₀ of the disclosed compounds (including the compounds of Table 1, table 2, and example) was determined using the CellTiter-Meiluncell luminescence cell viability assay kit from Meinai Bio Inc. The specific procedure was as follows, tumor cells were individually seeded in 96-well cell culture plates at the seeding densities of Table B. The next day, the test compounds of the present disclosure were serially diluted. The dilution operation can be performed following one of (1) a first dilution method in which the test compound of the present disclosure (including the compounds of tables 1, 2 and the compounds of examples) is subjected to 5-fold gradient dilution from a maximum concentration of 2000. Mu.M, and 9 concentrations (2000, 400, 80, 16, 3.2, 0.64, 0.128, 0.0256, 0.00512. Mu.M) are set in total from high to low. Subsequently, 0.5. Mu.L of the test compound of the present disclosure was pipetted into 96-well plates containing test cells, respectively, each well containing 100. Mu.L of cell culture medium, and the final test concentrations of the test compound in each well reached 10, 2, 0.4, 0.08, 0.016, 0.0032, 0.00064, 0.000128, 0.0000256. Mu.M, respectively. Or (2) alternatively, a second dilution method may be employed in which the test compounds of the present disclosure (including the compounds of tables 1, 2 and the compounds of the examples) are subjected to a 50-fold gradient dilution from a maximum concentration of 100. Mu.M, with a total of 2 concentrations (100. Mu.M, 2. Mu.M). In a 96-well plate, diluted compounds to be tested in the present disclosure and corresponding detection reagents are added to each well to ensure that the final test concentrations of the compounds to be tested in each well reach 500nM and 10nM, respectively, in order to evaluate the inhibitory activity of the compounds to be tested on tumor cell proliferation at these two concentration levels. The test procedure (similar to the procedure for 100. Mu.M concentration and the procedure for gradient concentration obtained by the first dilution method) will be described below with diluted 2. Mu.M test compound as an example.

0.5. Mu.L of the diluted compounds of the present disclosure (including the compounds of tables 1,2 and example compounds) described above was added to 100. Mu.L of the inoculated cells, and the final test compound concentration was 10nM. After treating cells for a period of time, a cell activity assay reagent is added to the culture medium according to the instructions of the kit for performing the cell activity assay. The negative control was DMSO and the control was the corresponding commercial immunomodulatory drugs (including lenalidomide (lenalidomide) and pomalidomide (pomalidomide)), all treated cells in the same manner as the presently disclosed compounds. Inhibition of cell growth by compounds of the present disclosure was plotted by PRISM GRAPHPAD software and compound IC ₅₀ of the present disclosure was counted therefrom. TABLE B inoculation procedure and treatment time of tumor cells

The results of inhibiting tumor cell proliferation are shown in tables I-1 to I-8. TABLE I-1 inhibitory Activity (inhibition ratio%) of the compounds of the present disclosure against proliferation of human myelomonocytic leukemia cells MV-4-11 In Table I-1, symbols 1a1, 1a2, 1a3, 1a4, 1a5, 1a6, 1a7, 1a8, 1a9, 1a10, 1a11 and 1a12 have the meanings given below ：-10％<1a1<0,0＜1a2<5％,5％≤1a3<10％,10％≤1a4<20％,20％≤1a5＜30％,30％≤1a6<40％,40％≤1a7<50％,50％≤1a8<60％,60％≤1a9<70％,70％≤1a10<80％,80％≤1a11≤100％,100％<1a12≤105％. Table I-2: inhibitory activity (% inhibition of proliferation) of the compounds of the present disclosure on MM.1S of human multiple myeloma cells In Table I-2, symbols 1b1, 1b2, 1b3, 1b4, 1b5, 1b6, 1b7, 1b8, 1b9, and 1b10 have the meanings as ：0<1b1<10％,10％≤1b2<20％,20％≤1b3<30％,30％≤1b4<40％,40％≤1b5<50％,50％≤1b6<60％,60％≤1b7<70％,70％≤1b8<80％,80％≤1b9≤100％,100％<1b10≤105％. Table I-3 below, the inhibitory activity (inhibition ratio%) of the compounds of the present disclosure on proliferation of human small cell lung cancer H196 In Table I-3, symbols 1c1, 1c2, 1c3, 1c4, 1c5, 1c6, 1c7, 1c8, 1c9, and 1c10 have the meanings given below ：0＜1c1<10％,10％≤1c2<20％,20％≤1c3<30％,30％≤1c4<40％,40％≤1c5<50％,50％≤1c6<60％,60％≤1c7<70％,70％≤1c8<80％,80％≤1c9≤100％,100％<1c10≤105％. Table I-4: inhibitory activity (% inhibition) of compounds of the present disclosure on proliferation of human pancreatic cancer cells CFPAC-1In Table I-4, symbols 1d1, 1d2, 1d3, 1d4, 1d5, 1d6, 1d7, 1d8, 1d9, and 1d10 have the meanings given below ：0<1d1＜10％,10％≤1d2<20％,20％≤1d3<30％,30％≤1d4<40％,40％≤1d5<50％,50％≤1d6<60％,60％≤1d7<70％,70％≤1d8<80％,80％≤1d9≤100％,100％<1d10≤105％. Table I-5: inhibitory activity (% inhibition) of the compounds of the present disclosure on proliferation of human malignant melanoma cells A375In Table I-5, symbols 1e1, 1e2, 1e3, 1e4, 1e5, 1e6, 1e7, 1e8, 1e9, and 1e10 have the meanings given in Table I-6 below ：0＜1e1<10％,10％≤1e2<20％,20％≤1e3<30％,30％≤1e4<40％,40％≤1e5<50％,50％≤1e6<60％,60％≤1e7<70％,70％≤1e8<80％,80％≤1e9≤100％,100％<1e10≤105％. Table I-6: inhibitory activity (% inhibition of proliferation) of the compounds of the present disclosure on human B lymphomatoid cells RPMI-8226In Table I-6, symbols 1f1, 1f2, 1f3, 1f4, 1f5, 1f7, 1f8, 1f9, and 1f10 have the meanings as ：0＜1f1＜10％,10％≤1f2＜20％,20％≤1f3＜30％,30％≤1f4<40％,40％≤1f5<50％,50％≤1f65＜60％,60％≤1f7<70％,70％≤1f8＜80％,80％≤1f9≤100％,100％<1f10≤105％. Table I-7 below, inhibitory activity (% inhibition) of the compounds of the present disclosure on proliferation of human diffuse large B lymphoma cell TMD8In Table I-7, symbols 1g1, 1g2, 1g3, 1g4, 1g5, 1g6, 1g7, 1g8, 1g9, and 1g10 have the meanings given below ：0＜1g1＜10％,10％≤1g2<20％,20％≤1g3<30％,30％≤1g4<40％,40％≤1g5<50％,50％≤1g6<60％,60％≤1g7<70％,70％≤1g8<80％,80％≤1g9≤100％,100％<1g10≤105％. Table I-8: inhibitory activity of a compound of the present disclosure on tumor cell proliferation (IC ₅₀, nM)Note that in Table I-8, the symbols A++, A+, A, B, C, D, E and F have the meanings indicated below as ：0＜A+++≤1nM;1nM<A++≤10nM;10nM＜A+≤50nM;50nM<A≤100nM;100nM<B≤500nM;500nM<C≤1000nM;1000nM<D≤5000nM;5000nM<E≤10000nM;F>10000nM. symbol "-" indicating undetected.

The results show that the compounds of the present disclosure (including the compounds of tables 1,2 and examples) have a significant inhibitory effect on proliferation of MV-4-11 cells (human myelomonocytic leukemia cells), mm.1s cells (human multiple myeloma cells), H196 cells (human small cell lung cancer cells), CFPAC-1 cells (human pancreatic cancer cells), a375 cells (human malignant melanoma cells), RPMI-8236 cells (human B lymphomatosis cells), and TMD8 cells (human diffuse large B lymphomatosis cells) (as shown in tables I-1 to I-8), with the inhibitory effect being superior to the corresponding positive control.

Western Blot (Western Blot) assay

The effect of the compounds of the present disclosure on target protein expression in cells was detected using conventional Western immunoblotting (Western Blot).

(1) Cell plating and protein harvesting hBMC cells with a cell density of 1X 10 ⁶/mL were resuscitated according to PBMC cell resuscitator protocol (Miaoshun (Shanghai) Biotechnology Co., ltd.) and treated with the compounds of the present disclosure (including the compounds of Table 1 and the compounds of the examples) at concentrations of 500nM and 50 nM. A negative control group (DMSO) and a positive control group, corresponding to commercial immunomodulatory drugs (lenalidomide (lenalidomide)), were also provided, all of which treated cells in the same manner as the disclosed compounds. After 24 hours of compound treatment, the cells were collected, lysed by addition of RIPA protein lysate containing protease inhibitors, placed on ice for 30 minutes and centrifuged. The supernatant was collected, and the resulting supernatant was the total cell protein extracted. The protein concentration of the supernatant was determined by the conventional BCA method (Bicinchoninc acid procedure).

(2) After 5X SDS-containing loading buffer was added to the collected supernatant and denatured at 95℃for 5 minutes, polyacrylamide gel SDS-PAGE was performed, followed by transfer to nitrocellulose membrane (0.45. Mu.M NC membrane), blocking with blocking solution at room temperature for 1 hour, and then antibody incubation and development were performed according to the antibody instructions of CELL SIGNALING Technology.

The half degradation concentration (the concentration of the drug corresponding to 50% of protein degradation, namely DC ₅₀) is read by comparing the gray value of the corresponding Western blotting strip after the drug treatment with the gray value of the corresponding Western blotting strip after the blank DMSO treatment, and the read gray value is the range of the drug concentration when the gray value of the corresponding Western blotting strip after the blank DMSO treatment is half of the gray value.

The calculation of the DC ₅₀ value can adopt imageJ software to read the gray value of the corresponding Western blotting band after the drug treatment. And (5) fitting a relation curve between the drug concentration and the gray value to calculate the drug concentration when the corresponding gray value is half.

Protein residual% refers to the amount of protein of interest remaining in the cell after treatment of hPBMC cells with the protein degrading agent compound.

The method for calculating the residual protein content comprises the step of utilizing Image J software to read gray values of corresponding Western blotting strips after treatment of a drug (protein degradation agent). Dividing the gray value of the corresponding Western blotting band after the drug treatment by the gray value of the corresponding Western blotting band of the internal reference protein, and carrying out normalization treatment on the obtained quotient value to obtain the relative residual content% of the target protein after the protein degradation agent treatment.

Target protein degradation rate%1-target protein residual content%

The results of the effect of the compounds of the present disclosure (including the compounds of tables 1,2 and the compounds of the examples) on the expression of a substrate protein in a cell are set forth in Table II-1 below. TABLE II-1 degradation results of the compounds of the present disclosure on substrate proteins WEE1, IKZF2, IKZF3, CK 1. Alpha. And GSPT1 (residual content of substrate protein%) Note that in Table II-1, A represents 0% or less and 80% or less of the residual amount of the substrate protein, and B represents 80% or less and < 100% or less of the residual amount of the substrate protein.

The degradation effect of the compound of the invention on target substrate proteins is shown in Table II-1 and FIG. 1. From the experimental results of Table II-1 and FIG. 1, it is understood that the compounds of the present invention can significantly degrade substrate proteins (e.g., WEE1 protein, IKZF1/2/3 protein, CK 1. Alpha. Protein, GSPT. Sup.1 protein, etc.). Compared with lenalidomide, the compound has remarkable improvement on the degradation efficiency of the induced substrate protein, and can selectively induce the degradation of the substrate protein, so that the compound can be used for treating indications related to the substrate protein.

Binding affinity assay of compounds of the present disclosure for CRBN:

CRBN binding ability of test compounds was measured by HTRF (homogeneous time-resolved fluorescence) method using CEREBLON BINDING KITS kit (Specification 10,000tests; reagent Cat. No. 64: BDCRBNPEH; supplier CISBIO company) by 1. According to the specification of CEREBLON BiNDING KITS kit, the test compounds of the present disclosure (including Table 1, The compounds of table 2 and the compounds of the examples) and lenalidomide were serially diluted, specifically using diluent #9 (1X) solution as the diluent, and a plurality of concentration gradients were set. The dilution operation can be performed following one of (1) a first dilution method in which the test compounds of the present disclosure (including the compounds of Table 1, table 2 and the compounds of the examples) are subjected to 5-fold gradient dilution from a maximum concentration of 40. Mu.M, and a total of 7 concentrations (40, 8, 1.6, 0.32, 0.064, 0.0128, 0.00256. Mu.M) are set from high to low. Subsequently, diluted test compounds of the present disclosure and corresponding test reagents were added to each well of a 96-well plate, respectively, and the final test concentrations of the test compounds in each well reached 10, 2, 0.4, 0.08, 0.016, 0.0032, 0.00064 μm, respectively. (2) Alternatively, a second dilution method may be employed in which the test compounds of the present disclosure (including the compounds of tables 1,2 and examples) are subjected to a 4-fold gradient dilution starting at a maximum concentration of 8. Mu.M, with a total of 2 concentrations (8. Mu.M, 2. Mu.M). In a 96-well plate, diluted compounds to be tested in the present disclosure and corresponding detection reagents are added to each well, and the final test concentration of the compounds to be tested in each well reaches 2 μm and 0.5 μm, respectively. Test procedure the diluted 8 μm test compound and lenalidomide solution are described as follows. 2. 2.5. Mu.L of the diluted 8. Mu.M test compound and lenalidomide solution were added to each well of the 96-well plate, respectively, with the same volume of diluent #9 (1X) solution (solvent control, std 0). Then, 2.5. Mu.L of human Cereblon WT GST-tagged protein solution was added to each well. Finally, 5. Mu.L of Thalidomide-Red reagent and GST Eu antibody working solution, which had been homogeneously mixed, were added to each well. The final concentration of test compound and lenalidomide in each well was 2 μm.3. The blank wells were sequentially filled with 2.5. Mu.L of diluent #9 (1X) solution, 2.5. Mu.L of PROTAC binding buffer solution, and 5. Mu.L of the well-mixed Thalidomide-Red reagent and GST Eu antibody working solution, respectively. 4. After the solution in each well was incubated at room temperature for 3 hours in a sealed manner, absorbance values at emission wavelengths of 620nm and 665nm were measured by HTRF method using Spark microplate reader (V3.1 SP 1), respectively. The corresponding CRBN binding inhibition ratio ：R _{Compounds of formula (I)} ＝OD 665nm _{Compounds of formula (I)} /OD 620nm _{Compounds of formula (I)} -OD 665nm _Control /OD 620nm _Control R_Std0＝OD 665nm_Std0/OD 620nm_Std0-OD 665nm _Control /OD 620nm _Control inhibition ratio (%) = (1-R _{Compounds of formula (I)} /R_Std0). Times.100 is calculated by adopting the following method that OD 665nm _{Compounds of formula (I)} is the absorbance value OD 620nm _{Compounds of formula (I)} of each hole of the compound to be tested at the emission wavelength 665nm, OD 665nm _Control is the absorbance value OD 620nm _Control of each hole of the compound to be tested at the emission wavelength 620nm, OD 665nm _Std0 is the absorbance value OD 665nm _Std0 of each hole of the blank control hole at the emission wavelength 620nm, and OD 620nm _Std0 of each hole of the solvent control hole at the emission wavelength 665nm is the absorbance value of each hole of the solvent control hole at the emission wavelength 620nm

The results are shown in tables III-1 and III-2 below. Table III-1 inhibition of HTRF of the compounds of the invention (including but not limited to the compounds of tables 1,2 and the compounds of the examples) (IC ₅₀, μM) In Table III-1, symbols a, b, c, d, e and f have the meanings 0<a≤0.5. Mu.M, 0.5. Mu.M < b≤1. Mu.M, 1. Mu.M < c≤1.5. Mu.M, 1.5. Mu.M < d≤1.9. Mu.M, 1.9. Mu.M≤e≤10. Mu.M, 10. Mu.M < f. TABLE III-2 CRBN binding affinity screening of the compounds of the invention (including but not limited to the compounds of tables 1,2 and the compounds of the examples) at a concentration of 2. Mu.M, 0.5. Mu.M In Table III-2, the symbols a, a1, a2, a3, a4, a5, a6, a7 and a8 have the following meanings ：0％<a≤10％,10％<a1≤20％,20％<a2≤30％,30％<a3≤40％,40％<a4≤53％,53％<a5≤60％,60％<a6≤70％,70％<a7≤80％,80％<a8<100％.

The results in tables III-1 and III-2 demonstrate that the compounds of the present invention (including but not limited to the compounds of tables l, 2 and the various examples) have lower or comparable IC5 ₀ values or have higher inhibition rates, exhibiting stronger binding to CRBN than lenalidomide.

TNF-alpha Activity inhibition assay

PBMCs cells were cultured at 37 ℃ at 5% co ₂ and then seeded at 1x 10 ⁷ cells/well in 96-well plates. Test compounds (including the compounds of tables 1,2 and examples) were dissolved in DMSO and diluted to the corresponding concentrations such that the final DMSO concentration in the cell culture was no more than 0.5%. After 1h incubation with compound-containing or compound-free medium, cells were stimulated with lipopolysaccharide (LPS; 1 ng/ml) and continued to culture for 18-20 h, then the supernatant was collected, diluted with serum-free medium, assayed for TNF- α levels with ELISA kit, and IC ₅₀ was calculated at GRAPHPAD PRISM 7.0.0.

Down-regulation of TNF-alpha expression is an important factor in the anti-tumor action of an immunomodulator. After treatment with the compounds of the invention, TNF- α levels are dose-dependent inhibited.

Pharmacokinetic studies of the compounds of the present disclosure

Pharmacokinetic properties of the compounds of the present disclosure were tested using conventional pharmacokinetic experimental methods.

Test compounds of the present disclosure (including the compounds of tables 1,2 and the compounds of the examples) were orally administered to experimental animals and the pharmacokinetic properties of the compounds of the present disclosure were evaluated. The experimental animals used may be adult healthy rodents (e.g., mice, rats (e.g., sprague-Dawley (SD) rats), guinea pigs), or non-rodents (rabbits, dogs, and monkeys) as are commonly used in pharmacokinetic experiments. The experimental animal employed in the present disclosure is a mouse.

The experimental animals were divided into 2 groups, namely a control group (blank plasma collection) and an oral administration group (administration dose is 10mg/kg or 30 mg/kg). Blood samples are collected at predetermined sampling time points after administration, for example, blood collection time points of 0.25h, 0.5h, 1h, 2h, 4h, 8h, 24h after administration. Blank plasma was collected from the control group.

Plasma samples were pre-treated prior to analysis by adding 10. Mu.L of 50% acetonitrile and 200. Mu.L of an internal standard solution (the internal standard solution was an acetonitrile solution containing 50ng/ml dexamethasone) to 10. Mu.L of plasma samples. The plasma samples of the blank group were supplemented with the same volume of acetonitrile without the internal standard. And (3) mixing the treated samples uniformly by vortex, centrifuging, and taking supernatant for LC-MS/MS sample injection analysis.

After preparation of standard curves and QC samples, LC-MS/MS analysis was used to determine the compound concentration in the plasma samples tested. According to the blood concentration data determined by LC-MS/MS analysis, pharmacokinetic parameters of the compound to be tested are calculated respectively by using a pharmacokinetic calculation software WinNonlin v8.1 non-atrioventricular model.

The results show that the compounds of the present disclosure administered via the oral route of administration have good pharmacokinetic (DMPK) profiles and can be used as therapeutic drugs for oncology patients.

Effect of the compounds of the present disclosure on phytohemagglutinin or eBioscience ^TM cell stimulation mixture (PMA+Ionomycin) to induce PBMC release of inflammatory factors including TNF- α, IL-1α, IL-1β, GM-CSF, IL-2, IL-12, IL-4, IL-5

The inventors examined the effect of the compounds of the invention on Peripheral Blood Mononuclear Cells (PBMC) triggered by phytohemagglutinin or eBioscience ^TM cell-stimulating complex (comprising PMA and Ionomycin) to release a range of inflammatory factors including TNF- α, IL-2, IL-5, IL-12, IL-10, IL-1α, IL-6, IL-8, IFN- γ, IL-1β, granulocyte-macrophage colony-stimulating factor (GM-CSF), and the like. Studies have been reported to suggest that these inflammatory factors may play an important role in the development and progression of cancer, autoimmune diseases, infectious diseases, and inflammatory diseases. In autoimmune diseases such AS Rheumatoid Arthritis (RA), psoriatic arthritis (PsA), ankylosing Spondylitis (AS), the expression level of TNF- α is markedly elevated and acts by stimulating synovial cell proliferation and promoting inflammatory responses. IL-1α has been implicated in cancer, autoimmune diseases, infectious diseases, and other inflammatory diseases, and is involved in the inflammatory process of autoimmune diseases. In diseases such as rheumatoid arthritis and systemic lupus erythematosus, the increase in IL-1β can reflect the extent and activity of inflammatory responses. IL-2, IL-5, IL-10, IFN-gamma, GM-CSF are also associated with a variety of inflammatory and autoimmune diseases.

The following materials were used in this study:

VI.1 reagents and consumables

VI.2 Process

VI.2.1 cell resuscitation and plating

Preparing complete culture medium, preheating at 37 deg.C, taking out cells from liquid nitrogen tank, clamping the boundary between cover and bottle body, immersing in 37 deg.C warm water, shaking to make them melt as soon as possible, sucking out cell suspension, adding into centrifugal tube containing 10mL of complete culture medium, mixing, centrifuging at room temperature for 10min, discarding supernatant, adding complete culture medium, counting and regulating cell density, inoculating to 96-well plate at 75 μl/well to cell number of 1×10 ⁵ per well, and standing in culture box with 5% CO ₂ at high humidity and 37 deg.C for 2 hr.

VI.2.2 preparation of Compounds and addition to cell plates 1) preparation of test compounds (including the compounds of tables 1, 2 and example) 10mM stock solutions were prepared with DMSO. 2) The test compounds were diluted 10-fold with DMSO at the highest concentration of 1mM, giving 2 concentration gradients of compounds, i.e., 1mM and 0.1mM. 3) The test compounds were diluted with medium to 5 times the set final concentration of the corresponding effect. 4) The diluted compounds were added to the corresponding cell wells at 25. Mu.L/well according to the following layout. The final concentration of the compound was 1. Mu.M, 10-fold diluted, and 2 concentration points were set, i.e., 1. Mu.M and 0.1. Mu.M. 5) PHA or PMA+Ionomycin was added to the wells at 25. Mu.L/well after 1h to a final concentration of PHA of 1. Mu.g/mL (TNF-. Alpha., IL-10, IL-6, IL-1β, IFN-. Gamma., IL-2, IL-12p40, IL-1α, IL-8), respectively, or PMA of 81nM/mL (IL-4, IL-5, IL-13, GM-CSF and IL-17A), or Ionomycin of 1.34. Mu.M/mL (IL-4, IL-5, IL-13, GM-CSF and IL-17A), respectively. 6) The cell plates were incubated in a high humidity, 37℃and 5% CO ₂ incubator for 24h. The negative control was DMSO and the positive control was the corresponding commercial immunomodulatory drug (e.g., lenalidomide (lenalidomide)) that all treated cells in the same manner as the presently disclosed compounds. Cell plate layout:

VI.2.3 detection (1) centrifugation, aspiration of culture supernatant, detection of TNF- α, IL-10, IL-6, IL-1β, IFN- γ, IL-2, IL-12p40, IL-1α, IL-8, IL-4, IL-5, IL-13, GM-CSF and IL-17A cytokines in culture supernatant according to the flow CBA assay protocol. (2) The flow CBA experiment is carried out by diluting the standard substance and the sample according to a certain proportion so as to accurately and quantitatively analyze in detection, mixing the microspheres, namely mixing the capturing microspheres with the sample or the standard substance, and carrying out light-proof reaction for 1H. Mixing the antibody, namely mixing the capture antibody with a sample or a standard substance, and reacting for 2 hours in a dark place. The two steps are the core of the flow CBA technology, and the quantitative detection of the cytokines is realized through the combination of the microspheres and target molecules. Flow cytometry detection the mixture was detected using a flow cytometer. The flow cytometer excites fluorescent markers on the microspheres by laser light, and collects and analyzes fluorescent signals, thereby quantitatively determining cytokine concentration in the sample. (3) According to the data collected by flow cytometry, further analysis is required, data processing is usually performed using specialized software FACP, generating detailed cytokine concentrations (TNF- α, IL-10, IL-6, IL-1β, IFN- γ, IL-2, IL-12p40, IL-1α, IL-8, IL-4, IL-5, IL-13, GM-CSF and IL-17A) reporting inhibition%o = [ (Ac-As)/(Ac-Ab) ]. Times.100% As: OA (cell+PHA/PMA+Ionomycin+test compound) of the sample: ac (cell+PHA/PMA+Ionomycin+DMSO) of the positive cell control: ab (cell+Medium+DMSO) of the blank control (4) using software GRAPHPAD PRISM 6 and using calculation formula XY-analysis/Nonlinear regression(curve fit)/Doseresponse-Inhibition/log(inhibitor)vs.response-Variable slope(four parameters) to perform IC ₅₀ curve fitting and calculate IC ₅₀ values.

The results are set forth in Table IV below. TABLE IV inhibition of inflammatory factors by the compounds of the invention (including but not limited to the compounds of TABLE 1, TABLE 2 and the example compounds) at 1. Mu.M, 0.1. Mu.M concentration% Note that in table IV, symbols IV0, IV1, IV2, IV3, IV4, IV5, IV6, IV7, IV8, IV9, IV10, IV11, IV12, IV13, and IV14 have the meanings given below ：-320％≤IV0＜-200％,-200％≤IV1＜-100％,-100％≤IV2＜-50％,-50％≤IV3<-20％,-20％≤IV4＜0％,0％<IV5≤10％,10％<IV6≤20％,20％<IV7≤30％,30％<IV8≤40％,40％<IV9≤50％,50％<IV10≤60％,60％<IV11≤70％,70％<IV12≤80％,80％<IV13≤90％,90％<IV14<100％,100％≤IV15≤110％. symbol "-" indicating undetected.

Experimental results show that the compounds of the present disclosure (including the compounds of tables 1,2 and the compounds of examples) exhibit excellent regulatory ability in regulating cytokine production levels associated with inflammatory diseases, autoimmune diseases, and their inhibitory effect is more pronounced than that of the positive control drug lenalidomide. The positive control drug lenalidomide has an elevating effect on IL-2, can activate immune response, has an inhibiting or no obvious stimulation effect on IL-2, and has a great advantage in treating immune system diseases. The compounds of the present disclosure (including the compounds of tables 1,2 and the examples) have broad prospects for potential therapies for the treatment of a variety of inflammatory diseases, autoimmune diseases (such as rheumatoid arthritis, ankylosing spondylitis, psoriasis and its arthritis, systemic lupus erythematosus, atopic dermatitis, and suppurative sweat gland inflammation, etc.).

VII test of the efficacy of the Compounds of the present disclosure on imiquimod-induced psoriasis-like skin lesions in mice

The compounds of the present disclosure (test compounds, including the compounds of tables 1,2 and example) were orally and intragastrically administered to imiquimod-induced mice 1 time a day for 7 consecutive days, and the pharmacodynamic effects of the compounds of the present disclosure on imiquimod-induced skin psoriasis-like lesions in the back of mice were studied.

60C 57BL/6J female mice (purchased from Shanghai Laek laboratory animal Co., ltd.) were equally divided into 6 groups according to body weight, 10 in each group: Note ig. oral gavage, sc. subcutaneous injection, qd. once daily.

After the experimental animals were grouped, the backs of all mice were shaved, and the animals of each group, except the Control group, were topically applied with imiquimod cream 1 time a day for 7 consecutive days. The solvent control, positive control or test agent was also administered 1 time per day for 7 consecutive days according to the above table, respectively.

All clinical symptoms of each animal were observed at the beginning of the experiment and during the course of the experiment. Animal weights were weighed and recorded 1 time a day 2.

Score skin lesions general appearance score (PASI method) the change in skin lesions was observed in groups of mice 1 time a day for the last 3 days of model dosing. And (3) scoring the erythema, the scales and the infiltration thickening degree at the skin lesion by a PASI method, and adding the three points to form a total point. The PASI scoring criteria were 0 score, none, 1 score, mild, 2 score, moderate, 3 score, severe, 4 score, severe.

The skin lesions were photographed 1 time a day for the last 3 days of the modelling dosing.

Mice were euthanized by the method of inhalation of excess CO ₂ after the end of the experiment. The skin at 3 different parts of the back skin lesion was weighed and recorded using a 6mm punch and the average weight calculated.

Skin tissue homogenates at skin lesions were examined for IL-23p19, IL-12p40, IL-17, TNF-alpha content.

The local skin injury part is obtained by HE staining after fixed materials, and pathological grading (epidermis thickness, epidermis cytokeratinization degree, basal cell thickness and dermis inflammatory cell infiltration degree) is carried out according to grading standards of 0 score, none score, 1 score, light score, 2 score, medium score, 3 score, heavy score, 4 score and extremely heavy score.

Experimental data are expressed in mean±sd, and data between the two groups are statistically analyzed using SPSS, with p <0.05 considered significant differences.

Experimental results show that the compound has an improving effect on the skin psoriasis-like lesions of the back of the mice induced by imiquimod, and can be used for treating psoriasis.

Drug efficacy experiment of the compound of the present disclosure on CIA model rats induced by type II collagen

The compounds of the present disclosure (test substances, including the compounds of tables 1,2 and example) were orally and gastro-orally administered to bovine type II collagen (Chondrex company) induced Wistar rats 1 time a day for 21 consecutive days to study the pharmacodynamic effects of the compounds of the present disclosure on the rat arthritis model (CIA).

The molding composition was prepared by dissolving 10mg of CII (Immunization Grade Bovine Type II Collagen, available from Chondrex) in 5mL of 0.05M acetic acid solution, allowing the solution to dissolve sufficiently, and allowing the solution to stand overnight at 4℃in the absence of light. In the test, 2mg/mL of CII solution was mixed with 4mg/mL of complete Freund's adjuvant (Complete Freunds Adjuvant, CFA, available from Chondrex) solution in equal volumes under ice bath conditions and emulsified thoroughly into an emulsion.

10 Wistar rats (purchased from beijing vernalia laboratory animal technologies limited) were randomly selected as a Control group on day 0 and were not immunized. The remaining 100 Wistar rats were given a first immunization by intradermal injection of an equal volume of an emulsion prepared by mixing CII (2 mg/mL) and CFA (4 mg/mL). A second boost was performed on day 7. On days 10-14, i.e. 3-7 days after the second boost immunization, the score of the onset foot AI (ArthritisIndex) is 1-2, 50 animals are selected from the model animals, and are divided into 5 groups according to the weight, foot volume and AI score, wherein each group comprises 10 animals: Note that ig is infused orally and sc. is subcutaneously injected

3-7 Days after the second immunization enhancement, starting to respectively administer the solvent control, the positive control drug or the test object to each group of animals according to the table by oral gavage (or subcutaneous injection) after the AI score of the foot to be treated reaches 1-2 times per day for 21 continuous days.

Starting 3 days after the second boost, the bilateral hind toe volumes were measured 2 times per week and recorded.

And (3) foot volume measurement, namely marking the position by drawing a line at the ankle joint of the rat by using a marker pen before measurement, and clearing the numerical value of the instrument after adding clean water into the instrument to prepare for measurement. The hind limb of the rat is put into water so that the marking line at the ankle joint is positioned on the surface of the liquid, and the foot pedal reading is stepped on at the moment, so that the foot volume of the rat is obtained. After the measurement is finished, the pedal is stepped down again to clear the next piece to be measured.

Arthritis Index (AI) was scored by measuring foot volume 2 times per week while four toe swellings were scored, 0-4 points per foot, with a maximum score of 16 points per rat. Arthritis index (ARTHRITIS INDEX) scoring criteria:

The beginning of administration is marked as day 0, and after 5 days of administration, namely 2 hours after 5 days of administration, blood is collected from jugular vein of experimental animal, and the experimental animal stands for more than 30 minutes, serum is centrifugally separated and frozen at-80 ℃, and serum TNF-alpha, IL-1 beta and IL-6 are detected by ELISA method.

After the end of the experiment, the animals were euthanized by the inhaled excess CO ₂ method. Spleen and thymus of the animal were collected, weighed and organ coefficients were calculated.

Pathological detection, namely fixing a lateral foot joint tissue in 10% neutral formalin solution, embedding paraffin after decalcification, and performing pathological observation by using HE staining for preparing pathological sections. The observation indexes are 1. Synovial inflammatory cells (lymphocytes, plasma cells) infiltration, 2. Synovial tissue hyperplasia, 3. Synovial pannus, 4. Synovial surface cellulose necrosis. The scoring and counting method comprises five grades of 0,1,2,3 and 4, namely, 0 is not seen, 1 is mild, 2 is moderate, 3 is severe and 4 is extremely severe.

Experimental data are expressed in mean±sem, and data between the two groups are analyzed using Excel-T test, p <0.05 is considered to be significantly different. Scoring data were analyzed using the SPSS nonparametric test Mann-Whitney U test, with p <0.05 considered significant differences.

Experimental results show that the compound disclosed by the invention can regulate the serum inflammatory factor level of bovine type II collagen-induced CIA model rats, has obvious improvement effect on limb swelling of rats, and can be used for treating arthritis.

The foregoing has shown and described the basic principles, principal features and advantages of the invention. It will be understood by those skilled in the art that the present invention is not limited to the above-described embodiments, and that various changes and modifications may be made therein without departing from the spirit and scope of the invention as claimed. The scope of the invention is defined by the appended claims and equivalents thereof.

Claims (26)

a compound of formula (I) or a salt, enantiomer, stereoisomer, isotopically enriched analog, solvate or polymorph thereof, in Z represents C(O), CH ₂ or CD ₂ ; R _a1 , R _a2 , R _a3 and R _a4 each independently represent hydrogen, deuterium, halogen, C _1-6 alkyl, halogenated C _1-6 alkyl, deuterated C _1-6 alkyl, C _1-6 alkoxy, deuterated C _1-6 alkoxy or halogenated C _1-6 alkoxy; (R _a5 ) _m represents that the isoindoline ring attached thereto is optionally substituted by m R _a5 , each R _a5 being the same or different and independently representing deuterium, halogen, hydroxyl, thiol, nitro, amino, cyano, C _1-6 alkyl, halogenated C _1-6 alkyl, deuterated C _1-6 alkyl, C _1-6 alkoxy, deuterated C _1-6 alkoxy, halogenated C _1-6 alkoxy, C _2-6 alkenyl or C _2-6 alkynyl; m represents an integer 0, 1, 2 or 3; R stands for: wherein Ring _A1 represents a heterocyclylene group containing at least 2 nitrogen atoms, ( _Rd1 ) _n1 represents that Ring _A1 is optionally substituted by n1 _Rd1 groups, each _Rd1 independently represents deuterium, halogen, hydroxyl, thiol, nitro, amino, cyano, oxo, _C1-6 alkyl, deuterated _C1-6 alkyl, halogenated _C1-6 alkyl, halogenated _C1-6 alkoxy or _C1-6 alkoxy, and n1 represents an integer from 0 to 20; and R ₁ represents N(R _w ), wherein R _w represents hydrogen or C _1-3 alkyl, and R ₂ represents a bond, or R ₂ represents CH ₂ or C(O); or R ₁ represents a bond, and R ₂ represents N(R _w ), wherein R _w represents hydrogen or C _1-3 alkyl, or R ₂ represents N(R _w )C(O)*, wherein R _w represents hydrogen or C _1-3 alkyl, or R ₂ represents -N=CH-*; or R stands for: wherein _RX represents NH, -N=CH-* or N( _Rw )C(O)*, wherein _Rw represents hydrogen or _C1-3 alkyl; or R stands for: wherein Ring _A2 represents a heterocyclylene group containing one nitrogen atom, ( _Rd4 ) _n4 represents that Ring _A2 is optionally substituted by n4 _Rd4 groups, each _Rd4 independently represents deuterium, halogen, hydroxyl, thiol, nitro, amino, cyano, oxo, _C1-6 alkyl, deuterated _C1-6 alkyl, halogenated _C1-6 alkyl, halogenated _C1-6 alkoxy or _C1-6 alkoxy, and n4 represents an integer from 0 to 20; and Where R _y1 represents The symbol ** indicates the point of attachment to ring A ₂ ; and R _y2 represents N(R _w ) or N(R _w )C(O)*, wherein R _w represents hydrogen or C _1-3 alkyl; The symbol * in the above formulae indicates the point of attachment to R _c ; and R _c represents CR _c1 R _c2 , wherein R _c1 and R _c2 each independently represent H, deuterium, halogen, optionally substituted linear or branched alkyl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aryl or optionally substituted heteroaryl, or R _c represents a bond; Ring B represents a cycloalkylene group, a heterocyclylene group, an arylene group or a heteroarylene group, m1 represents an integer of 0 or 1, (R _d2 ) _n2 represents that Ring B is optionally substituted by n2 R _d2 groups, each R _d2 independently represents deuterium, C _1-6 alkyl, deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, C _1-6 alkoxy, halogenated C _1-6 alkoxy, halogen, amino, hydroxyl, mercapto, cyano, oxo, C _2-6 alkynyl or C _2-6 alkenyl, and n2 represents an integer of 0-20; and Ring C represents a heterocyclyl, a cycloalkyl, an aryl or a heteroaryl group, (R _d3 ) _n3 represents that Ring C is optionally substituted by n3 R _d3 groups, each R _d3 independently represents deuterium, C _1-6 alkyl, deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, C _1-6 alkoxy, halogenated C _1-6 alkoxy, halogen, amino, hydroxyl, thiol, cyano, oxo, C _2-6 alkynyl or C _2-6 alkenyl, and n3 represents an integer from 0 to 20; Provided that the following compounds are not included: 3-(5-((4-benzhydrylpiperazin-1-yl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4′-chloro-[1,1′-biphenyl]-2-yl)methyl)piperazin-1-yl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl)piperazin-1-yl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; and 3-(5-((4-(4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-carbonyl)piperazin-1-yl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione. The compound of formula (I) or its salt, enantiomer, stereoisomer, solvate or polymorph as claimed in claim 1, wherein (i) _Ra1 , _Ra2 , _Ra3 and _Ra4 each independently represent H; and/or (ii) Ring _A1 represents a 4- to 30-membered heterocyclylene group (including a 4- to 20-membered heterocyclylene group and a 4- to 15-membered heterocyclylene group) containing at least 2 nitrogen atoms, ( _Rd1 ) _n1 represents that Ring _A1 is optionally substituted by n1 _Rd1 groups, each _Rd1 is independently deuterium, halogen, hydroxyl, mercapto, nitro, amino, cyano, oxo, _C1-6 alkyl, deuterated _C1-6 alkyl, halo _C1-6 alkyl, halo _C1-6 alkoxy or _C1-6 alkoxy, and n1 represents an integer from 0 to 20; and/or (iii) R ₁ represents N(R _w ), wherein R _w represents hydrogen or C _1-3 alkyl, and R ₂ represents a bond; or (iv) R ₁ represents N(R _w ), wherein R _w represents hydrogen or C _1-3 alkyl, and R ₂ represents CH ₂ or C(O); or (v) R ₁ represents a bond, and R ₂ represents N(R _w ), wherein R _w represents hydrogen or C _1-3 alkyl; or (vi) R ₁ represents a bond, and R ₂ represents N(R _w )C(O)*, wherein R _w represents hydrogen or C _1-3 alkyl; or (vii) R ₁ represents a bond, and R ₂ represents -N=CH-*; and/or (viii) Ring _A2 represents a 4- to 30-membered heterocyclylene group (including a 4- to 20-membered heterocyclylene group and a 4- to 15-membered heterocyclylene group) containing one nitrogen atom, ( _Rd4 ) _n4 represents that Ring _A2 is optionally substituted by n4 _Rd4 groups, each _Rd4 is independently deuterium, halogen, hydroxyl, mercapto, nitro, amino, cyano, oxo, _C1-6 alkyl, deuterated _C1-6 alkyl, halo _C1-6 alkyl, _{halo C1-6} alkoxy or _C1-6 alkoxy, and n4 represents an integer from 0 to 20; and/or (iv) R _c represents CR _c1 R _c2 , wherein R _c1 and R _c2 each independently represent H, deuterium, halogen, optionally substituted linear or branched C _1-10 alkyl, optionally substituted C _3-30 cycloalkyl, optionally substituted C _5-30 aryl, optionally substituted _4-30 membered heterocyclyl or optionally substituted 5-30 membered heteroaryl, or R _c represents a bond; and/or (v) Ring B represents a 4- to 30-membered heterocyclylene, a C _3-30 cycloalkylene, a C _5-30 arylene or a 5- to 30-membered heteroarylene, m1 represents an integer of 0 or 1, (R _d2 ) _n2 represents that Ring B is optionally substituted by n2 R _d2 groups, each R _d2 is independently deuterium, C _1-6 alkyl, deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, C _1-6 alkoxy, halogenated C _1-6 alkoxy, halogen, amino, hydroxyl, mercapto, cyano, oxo, C _2-6 alkynyl or C _2-6 alkenyl, and n2 represents an integer of 0-20; and/or (vi) Ring C represents a C _3-30 cycloalkyl group, a 4- to 30-membered heterocyclyl group, a C _5-30 aryl group or a 5- to 30-membered heteroaryl group, (R _d3 ) _n3 represents that Ring C is optionally substituted by n3 R _d3 groups, each R _d3 is independently deuterium, C _1-6 alkyl, deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, C _1-6 alkoxy, halogenated C _1-6 alkoxy, halogen, amino, hydroxyl, mercapto, cyano, oxo, C _2-6 alkynyl or C _2-6 alkenyl, and n3 represents an integer from 0 to 20. The compound of formula (I) or a salt, enantiomer, stereoisomer, solvate or polymorph thereof according to claim 1, wherein R represents one of the following formulas: wherein each R _w independently represents hydrogen or C _1-3 alkyl; each ring _A1 independently represents a heterocyclylene group containing at least 2 nitrogen atoms, ( _Rd1 ) _n1 represents that ring _A1 is optionally substituted by n1 _Rd1 groups, each _Rd1 independently represents deuterium, halogen, hydroxyl, thiol, nitro, amino, cyano, oxo, _C1-6 alkyl, deuterated _C1-6 alkyl, halogenated _C1-6 alkyl, halogenated _C1-6 alkoxy or _C1-6 alkoxy, and n1 represents an integer from 0 to 20; Ring _A2 represents a heterocyclylene group containing 1 nitrogen atom, ( _Rd4 ) _n4 represents that Ring _A2 is optionally substituted by n4 _Rd4 groups, each _Rd4 independently represents deuterium, halogen, hydroxyl, mercapto, nitro, amino, cyano, oxo, _C1-6 alkyl, deuterated _C1-6 alkyl, halogenated _C1-6 alkyl, halogenated _C1-6 alkoxy or _C1-6 alkoxy, and n4 represents an integer from 0 to 20; and The symbol * indicates the point of attachment to R _c . The compound of formula (I) or a salt, enantiomer, stereoisomer, solvate or polymorph thereof as claimed in any one of claims 1 to 3, wherein (i) each ring _A1 independently represents a 4- to 20-membered heterocyclylene group (including a 4- to 15-membered heterocyclylene group) containing at least 2 nitrogen atoms, ( _Rd1 ) _n1 represents that ring _A1 is optionally substituted by n1 _Rd1 groups, each _Rd1 is independently deuterium, halogen, hydroxyl, mercapto, nitro, amino, cyano, oxo, _C1-6 alkyl, deuterated _C1-6 alkyl, halogenated _C1-6 alkyl, halogenated _C1-6 alkoxy or _C1-6 alkoxy, and n1 represents an integer from 0 to 20; or (ii) Ring _A2 represents a 4- to 20-membered heterocyclylene group (including a 4- to 15-membered heterocyclylene group) containing one nitrogen atom, ( _Rd4 ) _n4 represents that Ring _A2 is optionally substituted by n4 _Rd4 groups, each _Rd4 is independently deuterium, halogen, hydroxyl, mercapto, nitro, amino, cyano, oxo, _C1-6 alkyl, deuterated _C1-6 alkyl, halogenated _C1-6 alkyl, halogenated _C1-6 alkoxy or _C1-6 alkoxy, and n4 represents an integer from 0 to 20; and/or (iii) each of R _c1 and R _c2 independently represents H, deuterium, halogen, optionally substituted linear or branched C _1-6 alkyl, optionally substituted C _3-20 cycloalkyl (including optionally substituted C _3-15 cycloalkyl), optionally substituted C _5-20 aryl (including optionally substituted C _5-15 aryl), optionally substituted 4 to 20 membered heterocyclyl (including optionally substituted 4 to 15 membered heterocyclyl), or optionally substituted 5 to 20 membered heteroaryl (including optionally substituted 5 to 15 membered heteroaryl); and/or (iv) Ring B represents a 4- to 20-membered heterocyclylene (including a 4- to 15-membered heterocyclylene), a C _3-20 cycloalkylene (including a C _3-15 cycloalkylene), a C _5-20 arylene (including a C _5-15 arylene) or a 5- to 20-membered heteroarylene (including a 5- to 15-membered heteroarylene), m1 represents an integer of 0 or 1, (R _d2 ) _n2 represents that Ring B is optionally substituted by n2 R _d2 groups, each R _d2 is independently deuterium, C _1-6 alkyl, deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, C _1-6 alkoxy, halogenated C _1-6 alkoxy, halogen, amino, hydroxyl, thiol, cyano, oxo, C _2-6 alkynyl or C _2-6 alkenyl, and n2 represents an integer of 0-20; and/or (v) the ring C represents a C _3-20 cycloalkyl group (including a C _3-15 cycloalkyl group), a 4- to 20-membered heterocyclyl group (including a 4- to 15-membered heterocyclyl group), a C _5-20 aryl group (including a C _5-15 aryl group) or a 5- to 20-membered heteroaryl group (including a 5- to 15-membered heteroaryl group), (R _d3 ) _n3 represents that the ring C is optionally substituted by n3 R _d3 groups, each R _d3 is independently deuterium, C _1-6 alkyl, deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, C _1-6 alkoxy, halogenated C _1-6 alkoxy, halogen, amino, hydroxyl, thiol, cyano, oxo, C _2-6 alkynyl or C _2-6 alkenyl, and n3 represents an integer from 0 to 20. The compound of formula (I) or its salt, enantiomer, stereoisomer, solvate or polymorph as claimed in claim 1, wherein (i) Z represents C(O) or CH ₂ ; and/or (ii) each ring A ₁ independently represents a 1,3-diazetidinylidene, an imidazolidinylidene, a pyrazolidinylidene, a piperazinylidene, a diazaheptanylidene, a diazaoctanylidene, a diazabicyclo[3.1.1]heptanylidene, a diazabicyclo[2.2.1]heptanylidene, a diazabicyclo[3.2.1]octanylidene, a diazabicyclo[2.2.2]octanylidene, a 2,6-diazaspiro[3.3]heptanylidene, a 2,7-diazaspiro[3.5]nonanylidene, a 2,8-diazaspiro[4.5]decanylidene, a 3,9-diazaspiro[5.5]undecanylidene or an octahydropyrrolo[3,4-c]pyrroleylidene, which is optionally substituted with n1 R _d1 groups, and each R _d1 are each independently deuterium, halogen, hydroxyl, mercapto, nitro, amino, cyano, oxo, _C1-6 alkyl, deuterated _C1-6 alkyl, halogenated _C1-6 alkyl, halogenated _C1-6 alkoxy or _C1-6 alkoxy, and n1 represents an integer of 0-20 (e.g., an integer of 0-10); or (iii) the ring _A2 represents an azetidinyl, pyrrolidinyl, piperidinyl, dihydroxypiperidinyl, difluoropiperidinyl, azepanyl, octanyl, a monoazabridged ring subunit (e.g., a 6- to 20-membered monoazabridged ring subunit, such as a 6-azabicyclo[3.1.1]heptanyl subunit, a 3-azabicyclo[3.2.1]octanyl subunit and a quinuclidinyl subunit) or a monoazaspirosubunit (e.g., a 5- to 20-membered monoazaspirosubunit, such as a 3-azaspiro[5.5]undecyl subunit and a 7-azaspiro[3.5]nonanyl subunit), which is optionally substituted by n4 _Rd4 groups, each _Rd4 being independently deuterium, halogen, hydroxyl, thiol, nitro, amino, cyano, oxo, _C1-6 alkyl, deuterated C1-6 alkyl, halogenated _C1-6 alkyl, _{C 1-6} alkyl, halogenated C _1-6 alkoxy or C _1-6 alkoxy, and n4 represents an integer of 0-20 (e.g., an integer of 0-10); and/or (iv) R _c1 and R _c2 each independently represent: H, deuterium, halogen or optionally substituted linear or branched C _1-10 alkyl; or Cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, decahydronaphthyl, octahydropentalenyl, octahydro-1H-indenyl, spirocycloalkyl (e.g., _C5 - _C20 spirocyclyl, such as spiro[3.3]heptyl, spiro[2.5]octyl, spiro[3.5]nonyl, spiro[3.5]nonenyl, spiro[4.4]nonyl, spiro[4.5]decyl, spiro[4.5]decenyl, spiro[5.5]undecyl), p-menthanyl, m-menthanyl, or bridged cycloalkyl (e.g., _C6 -C20 _20- bridged ring group, such as adamantyl, noradamantyl, bornyl, norbornyl, bicyclo[2.2.1]heptyl, 2-oxobicyclo[2.2.1]heptyl or bicyclo[2.2.1]heptenyl), which is optionally substituted with one or more (e.g., 1-10) substituents each independently selected from deuterium, halogen, hydroxyl, mercapto, nitro, amino, cyano, oxo, C _1-6 alkyl, halo-substituted C _1-6 alkyl, deuterated C _1-6 alkyl, C _1-6 alkoxy, deuterated C _1-6 alkoxy, halo-substituted C _1-6 alkoxy, C _2-6 alkenyl and C _2-6 alkynyl; or azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothiophenyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, tetrahydropyridinyl, dihydroxypiperidinyl, difluoropiperidinyl, morpholinyl, thiomorpholinyl, azepanyl, azocanyl, dioxanyl, azepanyl, azocanyl, diazepanyl (e.g., 1,4-diazacycloheptyl, 4,5-diazacycloheptyl, 1,3-diazacycloheptyl), diazacycloheptyl, bridged heterocyclic groups (e.g., 6- to 20-membered bridged heterocyclic groups, such as 6-azabicyclo[3.1.1]heptyl, 2,5-diazabicyclo[2.2.1]heptyl, 3,6-diazabicyclo[3.1.1]heptyl, 3- ]octanyl, 3,8-diazabicyclo[3.2.1]octanyl, 3,8-diazabicyclo[3.2.1]octanyl, 2,5-diazabicyclo[2.2.2]octanyl and quinuclidine), and azaspirocyclyl (e.g., 5- to 20-membered azaspirocyclyl, such as 2,6-diazaspiro[3.3]heptyl, 2,7-diazaspiro[3.5]nonyl, 2,8-diazaspiro[4.5]decyl, 3,9-diazaspiro[5.5]undecyl, 3-azaspiro[5.5]undecyl and 7-azaspiro[3.5]nonyl), or octahydropyrrolo[3,4-c]pyrrolyl, which is optionally substituted by one or more (e.g., 1-10) groups each independently selected from deuterium, halogen, hydroxy, thiol, amino, cyano, oxo, C substituted by a substituent selected from C _1-6 alkyl, halogenated C _1-6 alkyl, deuterated C _1-6 alkyl, C _1-6 alkoxy, halogenated C _1-6 alkoxy, C _2-6 alkenyl and C _2-6 alkynyl; or Phenyl or naphthyl, which is optionally substituted by one or more (e.g., 1-7) substituents each independently selected from deuterium, halogen, hydroxy, mercapto, nitro, amino, cyano, C _1-6 alkyl, halo-substituted C _1-6 alkyl, deuterated C _1-6 alkyl, C _1-6 alkoxy, halo-substituted C _1-6 alkoxy, C _2-6 alkenyl _{, and C 2-6 alkynyl} ; or furyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, indolyl, isoindolyl, indolyl, benzofuranyl, chromanyl, isobenzofuranyl, benzothienyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, benzo[2,1,3]oxadiazolyl, benzo[ 2,1,3]thiadiazolyl, benzo[1,2,3]thiadiazolyl, 2-oxo-2,3-dihydro-1H-benzo[d]imidazolyl, benzo[b][1,4]oxazinyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl, quinolyl, isoquinolyl, 1,2,3,4-tetrahydroquinolyl, naphthyridinyl, cinnolinyl, quinazolinyl, quinoxalinyl, 1,2,3,4-tetrahydroquinoxalinyl, phthalazinyl, 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3 -a]pyrazinyl, 4,5,6,7-tetrahydrothieno[3,2-c]pyridinyl, 5-oxo-6,7-dihydrothieno[3,2-d]pyrimidinyl, thieno[2,3-d]pyrimidinyl, thieno[3,2-d]pyrimidinyl, isoxazolo[4,5-c]pyridinyl, isoxazolo[4,5-c]pyrimidinyl, isoxazolo[4,5-d]pyrimidinyl, pyrazolo[1,5-a]pyridinyl, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-a]pyridinyl, 1 H-pyrrolo[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, pyrrolo[2,1-b]thiazolyl, imidazo[2,1-b]thiazolyl, 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidinyl, or 6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidinyl, which may be substituted by one or more (e.g., 1-10) groups independently selected from deuterium, halogen, hydroxyl, thiol, nitro, amino, cyano, C and/or substituted by a substituent selected from the group consisting of C _1-6 alkyl, halogenated C _1-6 alkyl, deuterated _{C 1-6} alkyl, C _1-6 alkoxy, deuterated C _1-6 alkoxy, halogenated C _1-6 alkoxy, C _2-6 alkenyl and C _2-6 alkynyl; and/or (v) The ring B represents: cyclopropylene, cyclobutylene, cyclopentylene, cyclopentenylene, cyclohexylene, cyclohexenylene, cycloheptylene, cyclooctylene, decahydronaphthylene, octahydropentalenylene, octahydro-1H-indenylene, 2,3-dihydro-1H-indenylene, spirocycloalkylene (e.g., _C5 - _C20 spirocycloalkylene, such as spiro[3.3]heptanylene, spiro[2.5]octanylene, spiro[3.5]nonanylene, spiro[3.5]nonenylene, spiro[4.4]nonanylene, spiro[4.5]decanylene, spiro[4.5]decenylene, spiro[5.5]undecanylene), p-menthanylene, m-menthanylene, or bridged cycloalkylene (e.g., _C6 -C20 ₂₀ bridged cycloalkylene groups, such as adamantylene, noradamantylene, bornylene, norbornylene, bicyclo[2.2.1]heptanylene, 2-oxobicyclo[2.2.1]heptanylene or bicyclo[2.2.1]heptenylene), which are optionally substituted with 0-20 (e.g. 0-10) substituents each independently selected from deuterium, C _1-6 alkyl, deuterated C _1-6 alkyl, haloC _1-6 alkyl, C _1-6 alkoxy, haloC _1-6 alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C _2-6 alkynyl or C _2-6 alkenyl; or Azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, tetrahydrofuranyl, dihydropyranyl, tetrahydropyranyl, tetrahydrothiophenyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, tetrahydropyridinyl, dihydroxypiperidinyl, difluoropiperidinyl, morpholinyl, thiomorpholinyl, dioxane, thiophene, Azacycloheptane, azacyclooctanyl, diazacycloheptane group (e.g., 1,4-diazacycloheptane group, 4,5-diazacycloheptane group, 1,3-diazacycloheptane group), diazacyclooctanyl group, subbridged heterocyclic group (e.g., 6- to 20-membered subbridged heterocyclic group, e.g., 6-azabicyclo[3.1.1]heptane group, 2,5-diazabicyclo[2.2.1]heptane group), 1, 2, 3, 6-diazabicyclo[3.1.1]heptanylene, 3-azabicyclo[3.2.1]octanylene, 3, 8-diazabicyclo[3.2.1]octanylene, 2, 5-diazabicyclo[2.2.2]octanylene and quinuclidinylene), azaspirocyclyl (e.g., a 5- to 20-membered azaspirocyclyl, e.g., a 2, 6-diazaspiro[3.3]heptanylene, 2,7-diazaspiro[3.5]nonanediyl, 2,8-diazaspiro[4.5]decanediyl, 3,9-diazaspiro[5.5]undecanediyl, 3-azaspiro[5.5]undecanediyl and 7-azaspiro[3.5]nonanediyl), or octahydropyrrolo[3,4-c]pyrrolediyl, which is optionally substituted with 0-20 (e.g., 0-10) substituents each independently selected from deuterium, C _1-6 alkyl, deuterated C _1-6 alkyl, haloC _1-6 alkyl, C _1-6 alkoxy, haloC _1-6 alkoxy, halogen, amino, hydroxyl, thiol, cyano, oxo, C _2-6 alkynyl or C _2-6 alkenyl; or Phenylene or naphthylene, which is optionally substituted by 0-20 (e.g., 0-6) substituents each independently selected from deuterium, C _1-6 alkyl, deuterated C _1-6 alkyl, halo C _1-6 alkyl, C _1-6 alkoxy, halo C _1-6 alkoxy, halogen, amino, hydroxy, mercapto, cyano, C _2-6 alkynyl or C _2-6 alkenyl; or furylene, oxazolylene, isoxazolylene, oxadiazolylene, thienylene, thiazolylene, isothiazolylene, thiadiazolylene, pyrrolylene, imidazolylene, pyrazolylene, triazolylene, pyridinylene, pyrimidinylene, pyridazinylene, pyrazinylene, triazinylene, indolylene, isoindolylene, indolylene, benzofuranylene, chromanylene, isobenzofuranylene, benzothienylene, indazolylene, benzimidazolylene, benzoxazolylene, benzoisoxazolylene, benzothiazolylene, benzoisothiazolylene, benzotriazolylene oxazolyl, benzo[2,1,3]oxadiazolyl, benzo[2,1,3]thiadiazolyl, benzo[1,2,3]thiadiazolyl, 2-oxo-2,3-dihydro-1H-benzo[d]imidazolylidene, benzo[b][1,4]oxazinyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl, quinolinyl, isoquinolinyl, 1,2,3,4-tetrahydroquinolinyl, naphthyridinyl, cinnolinyl, quinazolinyl, quinoxalinyl, 1,2,3,4-tetrahydroquinoxalinyl, phthalazinyl, 5-[[(4-( ... ,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine subunit, 4,5,6,7-tetrahydrothieno[3,2-c]pyridinyl subunit, 5-oxo-6,7-dihydrothieno[3,2-d]pyrimidine subunit, thieno[2,3-d]pyrimidine subunit, thieno[3,2-d]pyrimidine subunit, isoxazolo[4,5-c]pyrimidine subunit, isoxazolo[4,5-c]pyrimidine subunit, isoxazolo[4,5-d]pyrimidine subunit, pyrazolo[1,5-a]pyridinyl subunit, pyrazolo[1,5 -a] pyrimidinyl, imidazo[1,2-a]pyrimidinyl, 1H-pyrrolo[3,2-b]pyrimidinyl, 1H-pyrrolo[2,3-b]pyrimidinyl, pyrrolo[2,1-b]thiazolyl, imidazo[2,1-b]thiazolyl, 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidinyl, or 6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidinyl, which is optionally substituted by 0-20 (e.g., 0-10) units each independently selected from deuterium, C and/or is substituted by a C _1-6 alkyl, a deuterated C _1-6 alkyl, a halogenated C _1-6 alkyl, a C _1-6 alkoxy, a halogenated C _1-6 alkoxy, a halogen, an amino, a hydroxyl, a mercapto, a cyano, a C _2-6 alkynyl or a C _2-6 alkenyl substituent; (vi) The ring C represents: Cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, decahydronaphthyl, octahydropentalenyl, octahydro-1H-indenyl, spirocycloalkyl (e.g., _C5 - _C20 spirocyclyl, such as spiro[3.3]heptyl, spiro[2.5]octyl, spiro[3.5]nonyl, spiro[3.5]nonenyl, spiro[4.4]nonyl, spiro[4.5]decyl, spiro[4.5]decenyl, spiro[5.5]undecyl), p-menthanyl, m-menthanyl, or bridged cycloalkyl (e.g., _C6 -C20 _20- bridged ring groups, such as adamantyl, noradamantyl, bornyl, norbornyl, bicyclo[2.2.1]heptyl, 2-oxobicyclo[2.2.1]heptyl or bicyclo[2.2.1]heptenyl), which are optionally substituted with 0-20 (e.g., 0-10) substituents each independently selected from deuterium, C _1-6 alkyl, deuterated C _1-6 alkyl, halo C _1-6 alkyl, C _1-6 alkoxy, halo C _1-6 alkoxy, halogen, amino, hydroxyl, mercapto, cyano, oxo, C _2-6 alkynyl and C _2-6 alkenyl; or azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothiophenyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, tetrahydropyridinyl, dihydroxypiperidinyl, difluoropiperidinyl, morpholinyl, thiomorpholinyl, azepanyl, azocanyl, dioxanyl, azepanyl, azocanyl, diazepanyl (e.g., 1,4-diazepanyl, 4,5-diazepanyl, 1,3-diazepanyl), diazepanyl, bridged heterocyclic groups (e.g., 6- to 20-membered bridged heterocyclic groups, such as 6-azabicyclo[3.1.1]heptyl, 2,5-diazabicyclo[2.2.1]heptyl, 3, 6-diazabicyclo[3.1.1]heptyl, 3-azabicyclo[3.2.1]octyl, 3,8-diazabicyclo[3.2.1]octyl, 2,5-diazabicyclo[2.2.2]octyl and quinuclidine), and azaspirocyclyl (e.g., 5- to 20-membered azaspirocyclyl, such as 2,6-diazaspiro[3.3]heptyl, 2,7-diazaspiro[3.5]nonyl, 2,8-diazaspiro[4.5]decyl, 3,9-diazaspiro[5.5]undecyl, 3-azaspiro[5.5]undecyl and 7-azaspiro[3.5]nonyl), or octahydropyrrolo[3,4-c]pyrrolyl, which is optionally substituted by 0-20 (e.g., 0-10) each independently selected from deuterium, C substituted with a substituent selected from C _1-6 alkyl, deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, C _1-6 alkoxy, halogenated C _1-6 alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C _2-6 alkynyl and C _2-6 alkenyl; or Phenyl or naphthyl, which is optionally substituted with 0-20 (e.g., 0-6) substituents each independently selected from deuterium, C _1-6 alkyl, deuterated C _1-6 alkyl, halo C _1-6 alkyl, C _1-6 alkoxy, halo C _1-6 alkoxy, halogen, amino, hydroxy, mercapto, cyano, C _2-6 alkynyl, and C _2-6 alkenyl; or furyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, indolyl, isoindolyl, indolyl, benzofuranyl, chromanyl, isobenzofuranyl, benzothienyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, benzo[2,1,3]oxadiazole yl, benzo[2,1,3]thiadiazolyl, benzo[1,2,3]thiadiazolyl, 2-oxo-2,3-dihydro-1H-benzo[d]imidazolyl, benzo[b][1,4]oxazinyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl, quinolyl, isoquinolyl, 1,2,3,4-tetrahydroquinolyl, naphthyridinyl, cinnolinyl, quinazolinyl, quinoxalinyl, 1,2,3,4-tetrahydroquinoxalinyl, phthalazinyl, 5,6,7,8-tetrahydro-[1,2, 4]triazolo[4,3-a]pyrazinyl, 4,5,6,7-tetrahydrothieno[3,2-c]pyridinyl, 5-oxo-6,7-dihydrothieno[3,2-d]pyrimidinyl, thieno[2,3-d]pyrimidinyl, thieno[3,2-d]pyrimidinyl, isoxazolo[4,5-c]pyridinyl, isoxazolo[4,5-c]pyrimidinyl, isoxazolo[4,5-d]pyrimidinyl, pyrazolo[1,5-a]pyridinyl, pyrazolo[1,5-a]pyrimidinyl, imidazole oxazolo[1,2-a]pyridinyl, 1H-pyrrolo[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, pyrrolo[2,1-b]thiazolyl, imidazo[2,1-b]thiazolyl, 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidinyl, or 6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidinyl, which is optionally substituted with 0-20 (e.g., 0-10) substituents each independently selected from deuterium, C _1-6 alkyl, deuterated C _1-6 alkyl, haloC _1-6 alkyl, C _1-6 alkoxy, haloC _1-6 alkoxy, halogen, amino, hydroxy, thiol, cyano, C _2-6 alkynyl, and C _2-6 alkenyl. The compound of formula (I) or its salt, enantiomer, stereoisomer, solvate or polymorph as claimed in claim 1, wherein (i) R represents one of the following structures: wherein the symbol * indicates the point of attachment to R _c ; and/or (ii) in the compound of formula (I) A section represents one of the following structures: The compound of formula (I) or a salt, enantiomer, stereoisomer, solvate or polymorph thereof as claimed in claim 1, which is selected from the compounds in Table 1. A compound of formula (I) or a salt, enantiomer, stereoisomer, solvate or polymorph thereof as claimed in any one of claims 1 to 7, which is a hydrohalide salt (including hydrochloride, hydrobromide), sulfate, citrate/citrate, maleate, lactate, lactobionate, L-tartrate, fumarate, L-malate, L-lactate, α-ketoglutarate, hippurate, D-glucuronate, D-gluconate, α-D-glucoheptonate, glycolate, mucate, L-ascorbate, orotate, picrate, glycinate, alanine, arginine, cinnamate, laurate, pamoate, sebacate, benzenesulfonate, methanesulfonate, ethanesulfonate, edisylate, formate, acetate, 2,2 dichloroacetate, pivalate, propionate, valerate, palmitate, triphenylacetate, 2-ethyl-succinate, iodate, nicotinate, L-pyroglutamate, L-proline, ferulate, 2-hydroxyethanesulfonate, nitrate, gentisate, cholate, salicylate, terephthalate, glutarate, adipate, stearate, oleate, undecenoate, camphorate, camphorsulfonate, dodecylsulfonate, phosphate, thiocyanate, dihydrogenphosphate, pyrophosphate, metaphosphate, oxalate, carbonate, malonate, benzoate, mandelate, succinate, pyruvate, p-chlorobenzenesulfonate, 1,5-naphthalenedisulfonate, 3-hydroxy-2-naphthoate, 1-hydroxy-2-naphthoate, 2-naphthalenesulfonate, trifluoroacetate, glycolate or p-toluenesulfonate. a compound of formula (I') or a salt, enantiomer, stereoisomer, isotopically enriched analog, solvate or polymorph thereof, in Z represents C(O), CH ₂ or CD ₂ ; R _a1 , R _a2 , R _a3 and R _a4 each independently represent hydrogen, deuterium, halogen, C _1-6 alkyl, halogenated C _1-6 alkyl, deuterated C _1-6 alkyl, C _1-6 alkoxy, deuterated C _1-6 alkoxy or halogenated C _1-6 alkoxy; (R _a5 ) _m represents that the isoindoline ring attached thereto is optionally substituted by m R _a5 , each R _a5 being the same or different and independently representing deuterium, halogen, hydroxyl, thiol, nitro, amino, cyano, C _1-6 alkyl, halogenated C _1-6 alkyl, deuterated C _1-6 alkyl, C _1-6 alkoxy, deuterated C _{1-6 alkoxy, halogenated C 1-6 alkoxy} , C _2-6 alkenyl, C _2-6 alkynyl or heterocyclyl, wherein the heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, C _1-6 alkyl and tert-butoxycarbonyl; m represents an integer 0, 1, 2 or 3; Ring _A1 represents a 4- to 30-membered heterocyclylene group containing at least 2 nitrogen atoms, ( _Rd1 ) _n1 represents that Ring _A1 is optionally substituted by n1 _Rd1 groups, each _Rd1 independently represents deuterium, halogen, hydroxyl, mercapto, nitro, amino, cyano, oxo, _C1-6 alkyl, deuterated _C1-6 alkyl, halogenated _C1-6 alkyl, halogenated _C1-6 alkoxy or _C1-6 alkoxy, and n1 represents an integer from 0 to 20; and R ₁ represents N(R _w ), wherein R _w represents hydrogen or C _1-3 alkyl optionally substituted with one or more substituents independently selected from the group consisting of optionally substituted aryl and optionally substituted heteroaryl, and R ₂ represents a bond; or R ₁ represents a bond, and R ₂ represents N(R _w ), wherein R _w represents hydrogen or C _1-3 alkyl; and _Re represents a bond, or _Re represents C(O)O, or _Re represents a structure of the following formula: R _e1 represents C(O), CH ₂ or halogenated CH ₂ ; Ring D represents an arylene group, (R _e2 ) _m2 represents that ring D is optionally substituted by m2 R _e2 groups, each R _e2 independently represents deuterium, C _1-6 alkyl, deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, C _1-6 alkoxy, halogenated C _1-6 alkoxy, halogen, amino, hydroxyl, mercapto, cyano, oxo, C _2-6 alkynyl or C _2-6 alkenyl, and m2 represents an integer from 0 to 20; and Ring E represents a nitrogen-containing heterocyclylene group, m4 represents an integer of 0 or 1, (R _e3 ) _m3 represents that Ring E is optionally substituted by m3 R _e3 groups, each R _e3 independently represents deuterium, C _1-6 alkyl, deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, C _1-6 alkoxy, halogenated C _1-6 alkoxy, halogen, amino, hydroxyl, mercapto, cyano, oxo, C _2-6 alkynyl or C _2-6 alkenyl, and m3 represents an integer of 0-20; The symbol # indicates the point of connection to R _f ; and _Rf represents a _C1-10 alkyl group, which is optionally substituted with one or more substituents independently selected from the group consisting of _halogen , optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted cycloalkyl, and _NR3R4 , wherein _R3 and _{R4 each} independently represent H, _C1-3 alkyl, or optionally substituted cycloalkyl; Provided that the following compounds are not included: 3-(5-((4-benzhydrylpiperazin-1-yl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; and 3-(5-((4-((4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl)piperazin-1-yl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione. The compound of formula (I') or its salt, enantiomer, stereoisomer, solvate or polymorph according to claim 9, wherein (i) _Ra1 , _Ra2 , _Ra3 and _Ra4 each independently represent H; and/or (ii) Ring _A1 represents a 4- to 20-membered heterocyclylene group containing at least 2 nitrogen atoms, ( _Rd1 ) _n1 represents that Ring _A1 is optionally substituted by n1 _Rd1 groups, each _Rd1 is independently deuterium, halogen, hydroxyl, mercapto, nitro, amino, cyano, oxo, _C1-6 alkyl, deuterated _C1-6 alkyl, halo _C1-6 alkyl, halo _C1-6 alkoxy or _C1-6 alkoxy, and n1 represents an integer from 0 to 20; and/or (iii) R ₁ represents N(R _w ), wherein R _w represents hydrogen or C 1-3 alkyl optionally substituted with one or more substituents independently selected from the group consisting of optionally substituted C _5-30 aryl and optionally substituted 5- to 30-membered _heteroaryl , and R ₂ represents a bond; or (iv) R ₁ represents a bond, and R ₂ represents N(R _w ), wherein R _w represents hydrogen or C _1-3 alkyl; and/or (v) _Re represents a bond, or _Re represents C(O)O; or (vi) Ring D represents a _C5-30 arylene group, ( _Re2 ) _m2 represents that Ring D is optionally substituted by m2 _Re2 groups, each _Re2 independently represents deuterium, _C1-6 alkyl, deuterated _C1-6 alkyl, halogenated _C1-6 alkyl, _C1-6 alkoxy, halogenated _C1-6 alkoxy, halogen, amino, hydroxyl, mercapto, cyano, oxo, _C2-6 alkynyl or _C2-6 alkenyl, and m2 represents an integer from 0 to 20; and/or (vii) Ring E represents a 4- to 30-membered nitrogen-containing heterocyclylene group, m4 represents an integer of 0 or 1, (R _e3 ) _m3 represents that Ring E is optionally substituted by m3 R _e3 groups, each R _e3 independently represents deuterium, C _1-6 alkyl, deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, C _1-6 alkoxy, halogenated C _1-6 alkoxy, halogen, amino, hydroxyl, mercapto, cyano, oxo, C _2-6 alkynyl or C _2-6 alkenyl, and m3 represents an integer of 0-20; and/or (viii) _Rf represents _C1-10 alkyl, which is optionally substituted with one or more substituents independently selected from the group consisting of halogen, optionally substituted _C5-30 aryl, optionally substituted _5- to 30-membered heteroaryl, optionally substituted 4- to 30-membered heterocyclyl, optionally substituted _C3-30 cycloalkyl, and _NR3R4 , wherein _R3 and _{R4 each} independently represent H, _C1-3 alkyl, or optionally substituted _C3-30 cycloalkyl; and/or (ix) R _a5 represents deuterium, halogen, hydroxy, mercapto, nitro, amino, cyano, C _1-6 alkyl, halo-substituted C _1-6 alkyl, deuterated C _1-6 alkyl, C _1-6 alkoxy, deuterated C _1-6 alkoxy, halo-substituted C _1-6 alkoxy, C _2-6 alkenyl, C _2-6 alkynyl, or a 4- to 20-membered heterocyclyl, which is optionally substituted with one or more substituents independently selected from the group consisting of halogen, C _1-6 alkyl, and tert-butoxycarbonyl; wherein the _C5-30 aryl group and the 5 to 30 membered heteroaryl group are each independently optionally substituted with one or more substituents selected from the group consisting of halogen, amino, hydroxyl, thiol, cyano, oxo, _C1-6 alkyl, deuterated _C1-6 alkyl, halogenated _C1-6 alkyl, _C1-6 alkoxy, halogenated _C1-6 alkoxy, _C2-6 alkynyl and _C2-6 alkenyl, and the 4 to 30 membered heterocyclyl group and the _C3-30 cycloalkyl group are each independently optionally substituted with one or more substituents selected from the group consisting of halogen, amino, hydroxyl, thiol, cyano, oxo, _C1-6 alkyl, deuterated _C1-6 alkyl, halogenated _C1-6 alkyl, _C1-6 alkoxy, halogenated _C1-6 alkoxy, _C2-6 alkynyl, _C2-6 alkenyl, tert-butoxycarbonyl and optionally substituted _C5-15 aryl, wherein the C The _5-15 aryl group is optionally substituted with one or more substituents selected from halogen, C _1-6 alkyl and C _1-6 alkoxy. The compound of formula (I') or its salt, enantiomer, stereoisomer, solvate or polymorph according to claim 9 or 10, wherein (i) Ring _A1 represents a 4- to 15-membered heterocyclylene group containing at least 2 nitrogen atoms, ( _Rd1 ) _n1 represents that Ring _A1 is optionally substituted by n1 _Rd1 groups, each _Rd1 is independently deuterium, halogen, hydroxyl, mercapto, nitro, amino, cyano, oxo, _{C1-6 alkyl} , deuterated _C1-6 alkyl, halo _C1-6 alkyl, halo _C1-6 alkoxy or _C1-6 alkoxy, and n1 represents an integer from 0 to 20; and/or (ii) R ₁ represents N(R ₂ ), wherein R ₂ represents hydrogen or C 1-3 alkyl optionally substituted with one or more substituents independently selected from the group consisting of optionally substituted C _5-20 aryl (including optionally substituted C _5-15 aryl) and optionally substituted 5- to 20-membered heteroaryl (including optionally substituted 5- to ₁₅ -membered heteroaryl), and R ₂ represents a bond; or (iii) ring D represents a _C5-20 arylene group (including a _C5-15 arylene group), ( _Re2 ) _m2 represents that ring D is optionally substituted by m2 _Re2 groups, each _Re2 independently represents deuterium, _C1-6 alkyl, deuterated _C1-6 alkyl, halogenated _C1-6 alkyl, _C1-6 alkoxy, halogenated _C1-6 alkoxy, halogen, amino, hydroxyl, mercapto, cyano, oxo, _C2-6 alkynyl or _C2-6 alkenyl, and m2 represents an integer from 0 to 20; and/or (iv) Ring E represents a 4- to 20-membered nitrogen-containing heterocyclylene group (including a 4- to 15-membered nitrogen-containing heterocyclylene group), m4 represents an integer of 0 or 1, (R _e3 ) _m3 represents that Ring E is optionally substituted by m3 R _e3 groups, each R _e3 independently represents deuterium, C _1-6 alkyl, deuterated _{C 1-6} alkyl, halogenated C _1-6 alkyl, C _1-6 alkoxy, halogenated C _1-6 alkoxy, halogen, amino, hydroxyl, mercapto, cyano, oxo, C _2-6 alkynyl or C _2-6 alkenyl, and m3 represents an integer of 0-20; and/or (v) _Rf represents _C1-10 alkyl, which is optionally substituted with one or more substituents independently selected from the group consisting of halogen, optionally substituted _C5-20 aryl (including optionally substituted _C5-15 aryl), optionally substituted _5- to 20-membered heteroaryl (including optionally substituted 5- to 15-membered heteroaryl), optionally substituted 4- to 20-membered heterocyclyl (including optionally substituted 4- to 15-membered heterocyclyl), optionally substituted _C3-20 cycloalkyl (including optionally substituted _C3-15 cycloalkyl) and _NR3R4 , wherein _R3 and _{R4 each} independently represent H, _C1-3 alkyl or optionally substituted _C3-20 cycloalkyl (including optionally substituted _C3-15 cycloalkyl); and/or (vi) R _a5 represents deuterium, halogen, hydroxy, mercapto, nitro, amino, cyano, C _1-6 alkyl, halo-substituted C _1-6 alkyl, deuterated C _1-6 alkyl, C _1-6 alkoxy, deuterated C _1-6 alkoxy, halo-substituted C _1-6 alkoxy, C _2-6 alkenyl, C _2-6 alkynyl, or a 4- to 15-membered heterocyclyl, which is optionally substituted with one or more substituents independently selected from the group consisting of halogen, C _1-6 alkyl, and tert-butoxycarbonyl; wherein the _C5-20 aryl and the 5-20 membered heteroaryl are each independently optionally substituted with one or more substituents selected from the group consisting of halogen, amino, hydroxy, thiol, cyano, oxo, _C1-6 alkyl, deuterated _C1-6 alkyl, halogenated _C1-6 alkyl, _C1-6 alkoxy, halogenated C1-6 alkoxy, C2-6 alkynyl and _C2-6 alkenyl, and the _4-20 membered heterocyclyl and the _C3-20 cycloalkyl are each independently optionally substituted with one or more substituents selected from the group consisting of halogen, amino, hydroxy, thiol, cyano, oxo, _C1-6 alkyl, deuterated C1-6 alkyl, halogenated _C1-6 alkyl, _C1-6 alkoxy, halogenated C1-6 alkoxy, C2-6 alkynyl, _C2-6 alkenyl, tert-butyloxycarbonyl and optionally substituted with one or more substituents selected from the group consisting of halogen, amino, hydroxy, thiol, cyano, oxo, C1-6 alkyl, deuterated _C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkoxy, halogenated _C1-6 alkoxy, _C2-6 alkynyl, _C2-6 alkenyl, tert-butyloxycarbonyl and optionally substituted with one or more substituents selected from the group consisting of halogen, C C _5-15 aryl substituted with a C _1-6 alkyl group and a C _1-6 alkoxy group. The compound of formula (I') or a salt, enantiomer, stereoisomer, solvate or polymorph thereof as claimed in any one of claims 9 to 11, wherein (i) Ring _A1 represents a 1,3-diazetidinylidene, an imidazolidinylidene, a pyrazolidinylidene, a piperazinylidene, a diazaheptanylidene, a diazaoctanylidene, a diazabicyclo[3.1.1]heptanylidene, a diazabicyclo[2.2.1]heptanylidene, a diazabicyclo[3.2.1]octanylidene, a diazabicyclo[2.2.2]octanylidene, a 2,6-diazaspiro[3.3]heptanylidene, a 2,7-diazaspiro[3.5]nonanylidene, a 2,8-diazaspiro[4.5]decanylidene, a 3,9-diazaspiro[5.5]undecanylidene or an octahydropyrrolo[3,4-c]pyrroleylidene, which is optionally substituted by n1 _Rd1 groups, each R _d1 is each independently deuterium, halogen, hydroxyl, mercapto, nitro, amino, cyano, oxo, _C1-6 alkyl, deuterated _C1-6 alkyl, halogenated _{C1-6 alkyl} , halogenated _C1-6 alkoxy or _C1-6 alkoxy, and n1 represents an integer of 0-20 (e.g., an integer of 0-10); and/or (ii) _R represents hydrogen or C _1-3 alkyl, wherein the C _1-3 alkyl is optionally substituted with one or more substituents selected from the group consisting of: Phenyl or naphthyl, which is optionally substituted by one or more (e.g., 1-7) substituents each independently selected from halogen, amino, hydroxy, mercapto, cyano, oxo, C _1-6 alkyl, deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, C _1-6 alkoxy, halogenated C _1-6 alkoxy, C _2-6 alkynyl, and C _2-6 alkenyl; and furyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, indolyl, isoindolyl, indolyl, benzofuranyl, chromanyl, isobenzofuranyl, benzothienyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, benzo[2,1,3]oxadiazolyl, benzo [2,1,3]thiadiazolyl, benzo[1,2,3]thiadiazolyl, 2-oxo-2,3-dihydro-1H-benzo[d]imidazolyl, benzo[b][1,4]oxazinyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl, quinolyl, isoquinolyl, 1,2,3,4-tetrahydroquinolyl, naphthyridinyl, cinnolinyl, quinazolinyl, quinoxalinyl, 1,2,3,4-tetrahydroquinoxalinyl, phthalazinyl, 5,6,7,8-tetrahydro-[1,2,4]triazolo[4, 3-a]pyrazinyl, 4,5,6,7-tetrahydrothieno[3,2-c]pyridinyl, 5-oxo-6,7-dihydrothieno[3,2-d]pyrimidinyl, thieno[2,3-d]pyrimidinyl, thieno[3,2-d]pyrimidinyl, isoxazolo[4,5-c]pyridinyl, isoxazolo[4,5-c]pyrimidinyl, isoxazolo[4,5-d]pyrimidinyl, pyrazolo[1,5-a]pyridinyl, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-a]pyridinyl, 1H-pyrrolo[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, pyrrolo[2,1-b]thiazolyl, imidazo[2,1-b]thiazolyl, 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidinyl, and 6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidinyl, which are optionally substituted with one or more (e.g., 1-10) substituents each independently selected from halogen, amino, hydroxy, thiol, cyano, oxo, C _1-6 alkyl, deuterated C _1-6 alkyl, halo-substituted C _1-6 alkyl, C _1-6 alkoxy, halo-substituted C _1-6 alkoxy, C _2-6 alkynyl, and C _2-6 alkenyl; and/or (iii) Ring D represents a phenylene group or a naphthylene group, which is optionally substituted by m2 R _e2 groups, each R _e2 independently represents deuterium, C _1-6 alkyl, deuterated C _1-6 alkyl, halo C 1-6 alkyl, C _1-6 alkoxy, halo C _1-6 alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C _2-6 alkynyl or C _2-6 alkenyl, and m2 represents an integer from 0 _to 20 (e.g., an integer from 0 to 10); and/or (iv) Ring E represents an azetidinyl group, a pyrrolidinyl group, an imidazolidinyl group, a pyrazolidinyl group, a piperidinyl group, a piperazinyl group, a tetrahydropyridinyl group, a dihydroxypiperidinyl group, a difluoropiperidinyl group, an azepanyl group, an azepanyl group, a diazepanyl group (e.g., a 1,4-diazacycloheptanyl group, a 4,5-diazacycloheptanyl group, a 1,3-diazacycloheptanyl group), a diazacyclooctanyl group, a nitrogen-containing bridged heterocyclic group (e.g., a 6- to 20-membered nitrogen-containing bridged heterocyclic group, such as a 6-azabicyclo[3.1.1]heptanyl group, a 2,5-diazabicyclo[2.2.1]heptanyl group, a 3,6-diazabicyclo[3.1.1]heptanyl group) 1-Hydroxy-1-pyrrole-2-yl]pyrrole-3-yl, 2-Hydroxy-1-pyrrole-4-yl, 2-Hydroxy-1-pyrrole-5-yl, 2-Hydroxy-1-pyrrole-6-yl, 2-Hydroxy-1-pyrrole-7-yl, 2-Hydroxy-1-pyrrole-8-yl, 2-Hydroxy-1-pyrrole-9-yl, 2-Hydroxy-1-pyrrole-10-yl, 2-Hydroxy-1-pyrrole-11-yl, 2-Hydroxy-1-pyrrole-12-yl, 2-Hydroxy-1-pyrrole-13-yl, 2-Hydroxy-1-pyrrole-8-yl, 2-Hydroxy-1-pyrrole-9-yl, 2-Hydroxy-1-pyrrole-14-yl, 2-Hydroxy-1-pyrrole-15-yl, 2-Hydroxy-1-pyrrole-16-yl, 2-Hydroxy-1-pyrrole-17-yl, 2-Hydroxy-1-pyrrole-18-yl, R _e3 is substituted with a C _1-6 alkyl group, each R _e3 independently represents deuterium, C _1-6 alkyl, deuterated C _1-6 alkyl, halogenated C 1-6 alkyl, C _1-6 alkoxy, halogenated C _1-6 alkoxy, halogen, amino, hydroxyl, mercapto, cyano, oxo, C _2-6 alkynyl or C _2-6 alkenyl, m3 represents an integer from 0 to 20 (e.g., an integer from 0 to 10), and m4 represents an integer from 0 or 1; and/or (v) _Rf represents a _{C1-10 alkyl} group, which is optionally substituted with one or more substituents independently selected from the group consisting of: halogen; Phenyl or naphthyl, which is optionally substituted by one or more (e.g., 1-7) substituents each independently selected from halogen, amino, hydroxy, mercapto, cyano, oxo, C _1-6 alkyl, deuterated C _1-6 alkyl, halo-substituted C _1-6 alkyl, C _1-6 alkoxy, halo-substituted C _1-6 alkoxy, C _2-6 alkynyl, and C _2-6 alkenyl; furyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, indolyl, isoindolyl, indolyl, benzofuranyl, chromanyl, isobenzofuranyl, benzothienyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, benzo[2,1,3]oxadiazolyl, benzo [2,1,3]thiadiazolyl, benzo[1,2,3]thiadiazolyl, 2-oxo-2,3-dihydro-1H-benzo[d]imidazolyl, benzo[b][1,4]oxazinyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl, quinolyl, isoquinolyl, 1,2,3,4-tetrahydroquinolyl, naphthyridinyl, cinnolinyl, quinazolinyl, quinoxalinyl, 1,2,3,4-tetrahydroquinoxalinyl, phthalazinyl, 5,6,7,8-tetrahydro-[1,2,4]triazolo[4, 3-a]pyrazinyl, 4,5,6,7-tetrahydrothieno[3,2-c]pyridinyl, 5-oxo-6,7-dihydrothieno[3,2-d]pyrimidinyl, thieno[2,3-d]pyrimidinyl, thieno[3,2-d]pyrimidinyl, isoxazolo[4,5-c]pyridinyl, isoxazolo[4,5-c]pyrimidinyl, isoxazolo[4,5-d]pyrimidinyl, pyrazolo[1,5-a]pyridinyl, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-a]pyridinyl, 1H-pyrrolo[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, pyrrolo[2,1-b]thiazolyl, imidazo[2,1-b]thiazolyl, 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidinyl, or 6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidinyl, which is optionally substituted with one or more (e.g., 1-10) substituents each independently selected from halogen, amino, hydroxy, thiol, cyano, oxo, C _1-6 alkyl, deuterated C _1-6 alkyl, haloC _1-6 alkyl, C _1-6 alkoxy, haloC _1-6 alkoxy, C _2-6 alkynyl, and C _2-6 alkenyl; azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothiophenyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, tetrahydropyridinyl, dihydroxypiperidinyl, difluoropiperidinyl, morpholinyl, thiomorpholinyl, azepanyl, azocanyl, dioxanyl, azepanyl, azocanyl, diazepanyl, Cycloheptyl (e.g., 1,4-diazacycloheptyl, 4,5-diazacycloheptyl, 1,3-diazacycloheptyl), diazacyclooctanyl, bridged heterocyclic groups (e.g., 6- to 20-membered bridged heterocyclic groups, such as 6-azabicyclo[3.1.1]heptyl, 2,5-diazabicyclo[2.2.1]heptyl, 3,6-diazabicyclo[3.1.1]heptyl, 3-azabicyclo[3 .2.1]octyl, 3,8-diazabicyclo[3.2.1]octyl, 3,8-diazabicyclo[3.2.1]octyl, 2,5-diazabicyclo[2.2.2]octyl and quinuclidine), and azaspirocyclyl (e.g., a 5- to 20-membered azaspirocyclyl, such as 2,6-diazaspiro[3.3]heptyl, 2,7-diazaspiro[3.5]nonyl, 2,8-diazaspiro[4.5]decyl, 3,9-diazaspiro[5.5]undecyl, 3-azaspiro[5.5]undecyl and 7-azaspiro[3.5]nonyl), or octahydropyrrolo[3,4-c]pyrrolyl, which is optionally substituted with one or more (e.g., 1-10) substituents each independently selected from the group consisting of halogen, amino, hydroxy, thiol, cyano, oxo, C C _1-6 alkyl, deuterated C _1-6 alkyl, halogenated C _1-6 alkyl, C _1-6 alkoxy, halogenated C _1-6 alkoxy, C _2-6 alkynyl, C _2-6 alkenyl, tert-butoxycarbonyl, and C _5-15 aryl which is optionally substituted with one or more (e.g., 1 to 5) substituents selected from halogen, C _1-6 alkyl and C _1-6 alkoxy; Cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, decahydronaphthyl, octahydropentalenyl, octahydro-1H-indenyl, spirocycloalkyl (e.g., _C5 - _C20 spirocyclyl, such as spiro[3.3]heptyl, spiro[2.5]octyl, spiro[3.5]nonyl, spiro[3.5]nonenyl, spiro[4.4]nonyl, spiro[4.5]decyl, spiro[4.5]decenyl, spiro[5.5]undecyl), p-menthanyl, m-menthanyl, and bridged cycloalkyl (e.g., _C6 ... _20- bridged cyclic groups, such as adamantyl, noradamantyl, bornyl, norbornyl, bicyclo[2.2.1]heptyl, 2-oxobicyclo[2.2.1]heptyl or bicyclo[2.2.1]heptenyl), which is optionally substituted with one or more (e.g., 1-10) substituents each independently selected from the group consisting of halogen, amino, hydroxy, mercapto, cyano, oxo, C _1-6 alkyl, deuterated C _1-6 alkyl, halo-substituted C _{1-6 alkyl, C 1-6 alkoxy} , halo-substituted C _1-6 alkoxy, C _2-6 alkynyl, C _2-6 alkenyl, tert-butoxycarbonyl, and C _5-15 aryl optionally substituted with one or more (e.g., 1-5) substituents selected from halogen, C _1-6 alkyl and C _1-6 alkoxy; NR ₃ R ₄ , wherein R ₃ and R ₄ each independently represent: H; C _1-3 alkyl; or Cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, decahydronaphthyl, octahydropentalenyl, octahydro-1H-indenyl, spirocycloalkyl (e.g., _C5 - _C20 spirocyclyl, such as spiro[3.3]heptyl, spiro[2.5]octyl, spiro[3.5]nonyl, spiro[3.5]nonenyl, spiro[4.4]nonyl, spiro[4.5]decyl, spiro[4.5]decenyl, spiro[5.5]undecyl), p-menthanyl, m-menthanyl, or bridged cycloalkyl (e.g., _C6 -C20 _20- bridged cyclic groups, such as adamantyl, noradamantyl, bornyl, norbornyl, bicyclo[2.2.1]heptyl, 2-oxobicyclo[2.2.1]heptyl or bicyclo[2.2.1]heptenyl), which is optionally substituted with one or more (e.g., 1-10) substituents each independently selected from the group consisting of halogen, amino, hydroxy, mercapto, cyano, oxo, C _1-6 alkyl, deuterated C _1-6 alkyl, halo-substituted C _{1-6 alkyl, C 1-6 alkoxy} , halo-substituted C _1-6 alkoxy, C _2-6 alkynyl, C _2-6 alkenyl, tert-butoxycarbonyl, and C _5-15 aryl optionally substituted with one or more (e.g., 1-5) substituents selected from halogen, C _1-6 alkyl and C _1-6 alkoxy. The compound of formula (I') or its salt, enantiomer, stereoisomer, solvate or polymorph as described in any one of claims 9 to 12, wherein (i) _Rw represents H or (ii) R _e represents a bond, C(O)O, Wherein the symbol # indicates the connection point with R _f ; (iii) _Rf represents: Methyl, isopropyl, tert-butyl, The compound of formula (I') according to claim 9, or a salt, enantiomer, stereoisomer, solvate or polymorph thereof, selected from the compounds in Table 2. A compound of formula (I') or a salt, enantiomer, stereoisomer, solvate or polymorph thereof as claimed in any one of claims 9 to 14, which is a hydrohalide salt (including hydrochloride, hydrobromide), sulfate, citrate/citrate, maleate, lactate, lactobionate, L-tartrate, fumarate, L-malate, L-lactate, α-ketoglutarate, hippurate, D-glucuronate, D-gluconate, α-D-glucoheptonate, glycolate, mucate, L-ascorbate, orotate, picrate, glycinate, alanine, arginine, cinnamate, laurate, pamoate, sebacate, benzenesulfonate, methanesulfonate, ethanesulfonate, edisylate, formate, acetate, 2, 2-dichloroacetate, pivalate, propionate, valerate, palmitate, triphenylacetate, 2-ethyl-succinate, iodate, nicotinate, L-pyroglutamate, L-proline, ferulate, 2-hydroxyethanesulfonate, nitrate, gentisate, cholate, salicylate, terephthalate, glutarate, adipate, stearate, oleate, undecenoate, camphorate, camphorsulfonate, dodecylsulfonate, phosphate, thiocyanate, dihydrogenphosphate, pyrophosphate, metaphosphate, oxalate, carbonate, malonate, benzoate, mandelate, succinate, pyruvate, p-chlorobenzenesulfonate, 1,5-naphthalenedisulfonate, 3-hydroxy-2-naphthoate, 1-hydroxy-2-naphthoate, 2-naphthalenesulfonate, trifluoroacetate, glycolate, or p-toluenesulfonate. A pharmaceutical composition comprising: A compound of formula (I) or a pharmaceutically acceptable salt thereof as claimed in any one of claims 1 to 8, and at least one pharmaceutically acceptable carrier or excipient; or A compound of formula (I') or a pharmaceutically acceptable salt thereof according to any one of claims 9 to 15, and at least one pharmaceutically acceptable carrier or excipient; and optionally a second therapeutic agent, such as an anticancer agent. A compound of formula (I), a compound of formula (I') or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 15, for use in preventing or treating a disease or condition associated with cereblon protein. The compound of formula (I), the compound of formula (I') or a pharmaceutically acceptable salt thereof according to claim 17, wherein the disease or condition associated with cereblon protein is selected from: tumors, infectious diseases, inflammatory diseases, autoimmune diseases, anemia, hemorrhagic shock, transplant rejection, multiple organ dysfunction syndrome (MODS), sarcoidosis, adult respiratory distress syndrome, cardiovascular disease, Richter syndrome (RS), acute liver failure or diabetes. The compound of formula (I), the compound of formula (I') or a pharmaceutically acceptable salt thereof according to claim 17, wherein the disease or condition associated with the cereblon protein is selected from the group consisting of: myeloma, including multiple myeloma, plasma cell myeloma, smoldering myeloma, smoldering multiple myeloma; myelofibrosis; bone marrow disease; myelodysplastic syndrome (MDS); previously treated myelodysplastic syndrome; transplant-related cancer; neutropenia; leukemia, including acute myeloid leukemia (AML), chronic myeloid leukemia (CML), chronic myeloid leukemia, acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), myelofibrosis; bone marrow disease; myelodysplastic syndrome (MDS); previously treated myelodysplastic syndrome; transplant-related cancer; neutropenia; leukemia, including acute myeloid leukemia (AML), chronic myeloid leukemia (CML), chronic myeloid leukemia, acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), myelofibrosis; myeloid ... B-cell leukemia (CLL), B-cell chronic lymphocytic leukemia, anemia associated with leukemia, acute B-cell leukemia, T-cell leukemia, acute T-lymphocytic leukemia, lymphoma cell leukemia, monocytic leukemia, myelomonocytic leukemia; lymphomas, including diffuse large B-cell lymphoma, non-Hodgkin's lymphoma, Hodgkin's lymphoma, anaplastic lymphoma, anaplastic large cell lymphoma, CD20-positive lymphoma, mantle cell lymphoma, follicular lymphoma (FL), Burkitt's lymphoma; marginal zone lymphoma (MZL); primary lymphoma, B-cell lymphoma, relapsed B-cell non-Hodgkin's lymphoma Hodgkin lymphoma, relapsed diffuse large B-cell lymphoma, relapsed mediastinal (thymic) large B-cell lymphoma, primary mediastinal (thymic) large B-cell lymphoma, relapsed transformed non-Hodgkin lymphoma, refractory B-cell non-Hodgkin lymphoma, refractory diffuse large B-cell lymphoma, refractory primary mediastinal (thymic) large B-cell lymphoma, refractory transformed non-Hodgkin lymphoma; thyroid cancer; melanoma; lung cancer, including adenocarcinoma, squamous cell carcinoma, non-small cell lung cancer, and small cell lung cancer; inflammatory myofibroblastic tumor; colorectal cancer; intestinal cancer; glioma; glioblastoma; ovarian cancer; bronchogenic carcinoma; prostate cancer; breast cancer, including triple-negative breast cancer Patients with carcinoma, incidental breast cancer, and Cowden disease; pancreatic cancer; central nervous system cancer; neuroblastoma; glioma; peripheral neuroepithelial tumor; extramedullary plasmacytoma; plasmacytoma; gastric cancer; gastrointestinal stromal tumor; esophageal cancer; colorectal adenocarcinoma; esophageal squamous cell carcinoma; liver cancer; renal cell carcinoma; bladder cancer; endometrial cancer; uterine cancer; head and neck cancer; brain cancer; oral cancer; sarcomas, including rhabdomyosarcoma, various adipose tumors, Ewing sarcoma/primitive neuroectodermal tumors (Ewing/PNETs), and leiomyosarcoma; urothelial carcinoma; basal cell carcinoma; oral squamous cell carcinoma; bile duct cancer; bone cancer; cervical cancer; skin cancer; Richter syndrome (Richter syndrome) sepsis syndrome; autoimmune diseases, including rheumatoid arthritis, autoimmune encephalomyelitis, ankylosing spondylitis, psoriasis, psoriatic arthritis, systemic lupus erythematosus, multiple sclerosis, recurrent oral ulcers, Kawasaki disease, polymyositis/dermatomyositis, Sjögren's syndrome, atopic dermatitis, hidradenitis suppurativa, gout, type 1 diabetes, urticaria, inflammatory bowel disease (including Crohn's disease and ulcerative colitis); keratoconjunctivitis sicca; inflammatory diseases, including Crohn's disease and ulcerative colitis, pneumonia, osteoarthritis, synovitis, systemic inflammatory response syndrome, airway inflammation, bronchitis; cerebral malaria diseases; infectious diseases, including viral pneumonia, AIDS, COVID-19 novel coronavirus infection, Gram-negative bacterial infection, Gram-positive bacterial infection, tuberculosis, etc.; septic shock; tuberculosis; bacterial meningitis; chronic obstructive pulmonary disease; asthma; hemorrhagic shock; organ (including kidney, heart, lung) or tissue transplant rejection; diabetes; sarcoidosis; adult respiratory distress syndrome; anemia; pediatric aplastic anemia; cardiovascular disease (such as coronary heart disease, congestive heart failure, myocardial infarction, atherosclerosis); multiple organ failure caused by cachexia and septic shock; or acute liver failure. Use of a compound of formula (I), a compound of formula (I') or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 15, or a pharmaceutical composition according to claim 15, for preparing a medicament for preventing or treating a disease or condition associated with cereblon protein. A method for treating or preventing a disease or condition associated with cereblon protein in a subject, comprising administering to the subject a therapeutically effective amount of a compound of formula (I), a compound of formula (I') or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 15, or a pharmaceutical composition according to claim 16. The use according to claim 20 or the method according to claim 21, wherein the disease or condition associated with the cereblon protein is selected from: tumors, infectious diseases, inflammatory diseases, autoimmune diseases, anemia, hemorrhagic shock, transplant rejection, multiple organ dysfunction syndrome (MODS), sarcoidosis, adult respiratory distress syndrome, cardiovascular disease, Richter syndrome (RS), acute liver failure or diabetes. The use of claim 20 or the method of claim 21, wherein the disease or condition associated with the cereblon protein is selected from the group consisting of: myeloma, including multiple myeloma, plasma cell myeloma, smoldering myeloma, smoldering multiple myeloma; myelofibrosis; bone marrow disease; myelodysplastic syndrome (MDS); previously treated myelodysplastic syndrome; transplant-related cancer; neutropenia; leukemia, including acute myeloid leukemia (AML), chronic myeloid leukemia (CML), chronic myeloid leukemia, acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), and leukemia. LL), B-cell chronic lymphocytic leukemia, anemia associated with leukemia, acute B-cell leukemia, T-cell leukemia, acute T-lymphocytic leukemia, lymphoma cell leukemia, monocytic leukemia, myelomonocytic leukemia; lymphomas, including diffuse large B-cell lymphoma, non-Hodgkin lymphoma, Hodgkin lymphoma, anaplastic lymphoma, anaplastic large cell lymphoma, CD20-positive lymphoma, mantle cell lymphoma, follicular lymphoma (FL), Burkitt's lymphoma; marginal zone lymphoma (MZL); primary lymphoma, B-cell lymphoma, relapsed B-cell non-Hodgkin lymphoma , recurrent diffuse large B-cell lymphoma, recurrent mediastinal (thymic) large B-cell lymphoma, primary mediastinal (thymic) large B-cell lymphoma, recurrent transformed non-Hodgkin's lymphoma, refractory B-cell non-Hodgkin's lymphoma, refractory diffuse large B-cell lymphoma, refractory primary mediastinal (thymic) large B-cell lymphoma, refractory transformed non-Hodgkin's lymphoma; thyroid cancer; melanoma; lung cancer, including lung adenocarcinoma, lung squamous cell carcinoma, non-small cell lung cancer, small cell lung cancer; inflammatory myofibroblastic tumor; colorectal cancer; intestinal cancer; brain glioma; glioblastoma astrocytoma; ovarian cancer; bronchogenic carcinoma; prostate cancer; breast cancer, including triple-negative breast cancer, occasional Patients with primary breast cancer and Cowden disease; pancreatic cancer; central nervous system cancers; neuroblastoma; glioma; peripheral neuroepithelial tumor; extramedullary plasmacytoma; plasmacytoma; gastric cancer; gastrointestinal stromal tumor; esophageal cancer; colorectal adenocarcinoma; esophageal squamous cell carcinoma; liver cancer; renal cell carcinoma; bladder cancer; endometrial cancer; uterine cancer; head and neck cancer; brain cancer; oral cancer; sarcomas, including rhabdomyosarcoma, various adipose tumors, Ewing sarcoma/primitive neuroectodermal tumors (Ewing/PNETs), and leiomyosarcoma; urothelial carcinoma; basal cell carcinoma; oral squamous cell carcinoma; bile duct cancer; bone cancer; cervical cancer; skin cancer; Richter syndrome (Richter syndrome) sepsis syndrome; autoimmune diseases, including rheumatoid arthritis, autoimmune encephalomyelitis, ankylosing spondylitis, psoriasis, psoriatic arthritis, systemic lupus erythematosus, multiple sclerosis, recurrent oral ulcers, Kawasaki disease, polymyositis/dermatomyositis, Sjögren's syndrome, atopic dermatitis, hidradenitis suppurativa, gout, type 1 diabetes, urticaria, inflammatory bowel disease (including Crohn's disease and ulcerative colitis); keratoconjunctivitis sicca; inflammatory diseases, including Crohn's disease and ulcerative colitis, pneumonia, osteoarthritis, synovitis, systemic inflammatory response syndrome, airway inflammation, bronchitis; cerebral malaria diseases; infectious diseases, including viral pneumonia, AIDS, COVID-19 novel coronavirus infection, Gram-negative bacterial infection, Gram-positive bacterial infection, tuberculosis, etc.; septic shock; tuberculosis; bacterial meningitis; chronic obstructive pulmonary disease; asthma; hemorrhagic shock; organ (including kidney, heart, lung) or tissue transplant rejection; diabetes; sarcoidosis; adult respiratory distress syndrome; anemia; pediatric aplastic anemia; cardiovascular disease (such as coronary heart disease, congestive heart failure, myocardial infarction, atherosclerosis); multiple organ failure caused by cachexia and septic shock; or acute liver failure. A method for preparing a compound of formula (I) as claimed in claim 1, comprising using a compound of formula (M1) and a compound of formula (M2) as starting materials to prepare a compound of formula (I): wherein _Ra1 , _Ra2 , _Ra3 , _Ra4 , ( _Ra5 ) _m , Z, R, Ring B, Ring C, ( _Rd2 ) _n2 , ( _Rd3 ) _n3 , and m1 are as defined in claim 1; and R _w3 represents CHO, COOH or wherein R _c2 is as defined in claim 1, and the group LE represents Cl, Br, I, OMs, OTs, or ONs; Where (1) -R _w1 -R _w2 represents And R represents or (2) -R _w1 -R _w2 represents And R represents or (3) -R _w1 -R _w2 represents -NH-NH ₂ , and R represents -NH-NH-; or (4) -R _w1 -R _w2 represents And R represents wherein R _w , Ring A ₁ , (R _d1 ) _n1 , Ring A ₂ and (R _d4 ) _n4 are as defined in claim 1 ; wherein when R _w3 represents CHO, R _c3 and R _c4 represent H; or When R _w3 represents COOH, R _c3 and R _c4 together form a carbonyl group; or When R _w3 represents When R _c3 represents H, and R _c4 is R _c2 . The method of claim 24, wherein (1) When R _w3 represents CHO, the compound of formula (M1) and the compound of formula (M2) undergo a reductive amination reaction to prepare a compound of formula (I), wherein R _c3 and R _c4 in the compound of formula (I) represent H; (2) When R _w3 represents COOH, the compound of formula (M1) undergoes an amide condensation reaction with the compound of formula (M2) to prepare the compound of formula (I), wherein R _c3 and R _c4 in the compound of formula (I) together form a carbonyl group; or (3) When R _w3 represents When the compound of formula (M1) undergoes an amine alkylation reaction with the compound of formula (M2) to prepare the compound of formula (I), wherein R _c3 in the compound of formula (I) represents H, and R _c4 is R _c2 . The method of claim 24, wherein When -R _w1 -R _w2 of the compound of formula (M1) represents When the compound of formula (M1) is prepared by reacting the compound of formula (M3) with the compound of formula (M4) as starting materials, Y represents F or Br; _W1 represents H, and _W2 represents an amino protecting group; or W ₁ represents an amino protecting group, and W ₂ represents H.