CA2417652A1 - Bicyclic heterocycles, pharmaceutical compositions containing these compounds, their use and processes for preparing them - Google Patents

Bicyclic heterocycles, pharmaceutical compositions containing these compounds, their use and processes for preparing them Download PDF

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Publication number
CA2417652A1
CA2417652A1 CA002417652A CA2417652A CA2417652A1 CA 2417652 A1 CA2417652 A1 CA 2417652A1 CA 002417652 A CA002417652 A CA 002417652A CA 2417652 A CA2417652 A CA 2417652A CA 2417652 A1 CA2417652 A1 CA 2417652A1
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bicyclic heterocycles
preparing
compounds
processes
pharmaceutical compositions
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CA002417652A
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French (fr)
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CA2417652C (en
Inventor
Frank Himmelsbach
Elke Langkopf
Birgit Jung
Stefan Blech
Flavio Solca
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Boehringer Ingelheim Pharma GmbH and Co KG
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D405/00Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/517Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • A61P11/02Nasal agents, e.g. decongestants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • A61P11/06Antiasthmatics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • A61P11/08Bronchodilators
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • A61P11/14Antitussive agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00Drugs for disorders of the urinary system
    • A61P13/12Drugs for disorders of the urinary system of the kidneys
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/06Antipsoriatics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • A61P35/02Antineoplastic agents specific for leukemia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • A61P35/04Antineoplastic agents specific for metastasis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/08Antiallergic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D405/00Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Pulmonology (AREA)
  • Dermatology (AREA)
  • Immunology (AREA)
  • Oncology (AREA)
  • Epidemiology (AREA)
  • Hematology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Urology & Nephrology (AREA)
  • Otolaryngology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

The invention relates to bicyclic heterocycles of general formula (I), in which Ra to Rd and X are defined as referred to in Claims Nos. 1 to 7, to their tautomers, their stereoisomers, and to their salts, particularly their physiologically compatible salts with inorganic or organic acids or bases, which have valuable pharmacological properties, in particular, an inhibitive effect on the signal transduction imparted by tyrosine kinases. The inventio n also relates to the use of said bicyclic heterocycles for treating diseases, especially tumor diseases, disorders of the lung and of the respiratory trac t, and to the production thereof.
CA002417652A 2000-08-26 2001-08-18 Bicyclic heterocycles, pharmaceutical compositions containing these compounds, their use and processes for preparing them Expired - Fee Related CA2417652C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE10042059A DE10042059A1 (en) 2000-08-26 2000-08-26 Bicyclic heterocycles, medicaments containing these compounds, their use and processes for their preparation
DE10042059.1 2000-08-26
PCT/EP2001/009533 WO2002018372A1 (en) 2000-08-26 2001-08-18 Bicyclic heterocycles, medicaments containing these compounds, their use, and methods for the production thereof

Publications (2)

Publication Number Publication Date
CA2417652A1 true CA2417652A1 (en) 2003-01-28
CA2417652C CA2417652C (en) 2008-10-28

Family

ID=7653946

Family Applications (1)

Application Number Title Priority Date Filing Date
CA002417652A Expired - Fee Related CA2417652C (en) 2000-08-26 2001-08-18 Bicyclic heterocycles, pharmaceutical compositions containing these compounds, their use and processes for preparing them

Country Status (8)

Country Link
EP (1) EP1315718B1 (en)
JP (1) JP4901055B2 (en)
AU (1) AU2001295481A1 (en)
CA (1) CA2417652C (en)
DE (2) DE10042059A1 (en)
ES (1) ES2296812T3 (en)
MX (1) MXPA03001725A (en)
WO (1) WO2002018372A1 (en)

Cited By (4)

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US8088782B2 (en) 2008-05-13 2012-01-03 Astrazeneca Ab Crystalline 4-(3-chloro-2-fluoroanilino)-7 methoxy-6-{[1-(N-methylcarbamoylmethyl)piperidin-4-yl]oxy}quinazoline difumarate form A
US8318752B2 (en) 2003-09-19 2012-11-27 Astrazeneca Ab 4-(3-chloro-2-fluoroanilino)-7-methoxy-6-{[1-(N-methylcarbamoyl-methyl)piperidin-4-yl]oxy}quinazoline, its pharmaceutically acceptable salts, and pharmaceutical compositions comprising the same
US8399667B2 (en) 2002-03-28 2013-03-19 Astrazeneca Ab 4-anilino quinazoline derivatives as antiproliferative agents
US8735410B2 (en) 2005-02-26 2014-05-27 Astrazeneca Ab Quinazoline derivatives as tyrosine kinase inhibitors

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EE04748B1 (en) 1999-06-21 2006-12-15 Boehringer Ingelheim Pharma Kg Bicyclic heterocyclic compounds, drugs containing these compounds, their use and methods for their preparation
DE60144284D1 (en) 2000-11-01 2011-05-05 Millennium Pharm Inc NITROGENIC HETEROCYCLIC COMPOUNDS AND METHOD FOR THE PRODUCTION THEREOF
US7019012B2 (en) 2000-12-20 2006-03-28 Boehringer Ingelheim International Pharma Gmbh & Co. Kg Quinazoline derivatives and pharmaceutical compositions containing them
CA2476008C (en) * 2002-03-30 2011-12-13 Boehringer Ingelheim Pharma Gmbh & Co. Kg Bicyclic heterocyclic compounds, pharmaceutical compositions containing these compounds, their use and process for preparing them
US6924285B2 (en) 2002-03-30 2005-08-02 Boehringer Ingelheim Pharma Gmbh & Co. Bicyclic heterocyclic compounds, pharmaceutical compositions containing these compounds, their use and process for preparing them
DE10214412A1 (en) * 2002-03-30 2003-10-09 Boehringer Ingelheim Pharma Bicyclic heterocycles, pharmaceutical compositions containing these compounds, their use and process for their preparation
EP2280003B1 (en) * 2002-07-15 2014-04-02 Symphony Evolution, Inc. Process for preparing receptor-type kinase modulators
NZ544472A (en) 2003-07-03 2009-04-30 Myriad Genetics Inc Compounds and therapeutical use thereof
US8309562B2 (en) 2003-07-03 2012-11-13 Myrexis, Inc. Compounds and therapeutical use thereof
DE10334226A1 (en) * 2003-07-28 2005-02-17 Boehringer Ingelheim Pharma Gmbh & Co. Kg Use of tyrosine kinase inhibitors for the treatment of inflammatory processes
JP2007500177A (en) * 2003-07-29 2007-01-11 アストラゼネカ アクチボラグ Piperidylquinazoline derivatives as tyrosine kinase inhibitors
GB0317665D0 (en) 2003-07-29 2003-09-03 Astrazeneca Ab Qinazoline derivatives
JP2005306839A (en) * 2003-08-29 2005-11-04 Takeda Chem Ind Ltd Bicyclic piperazine compound and its use
EP1661898A4 (en) * 2003-08-29 2009-04-15 Takeda Pharmaceutical BICYCLIC PIPERAZINE COMPOUND AND USE THEREOF
AU2004272345A1 (en) * 2003-09-16 2005-03-24 Astrazeneca Ab Quinazoline derivatives
ES2305844T3 (en) 2003-09-16 2008-11-01 Astrazeneca Ab DERIVATIVES OF QUINAZOLINE AS INHIBITORS OF THYROSINE KINASE.
US7456189B2 (en) 2003-09-30 2008-11-25 Boehringer Ingelheim International Gmbh Bicyclic heterocycles, medicaments containing these compounds, their use and processes for their preparation
DE10345875A1 (en) * 2003-09-30 2005-04-21 Boehringer Ingelheim Pharma Bicyclic heterocycles, pharmaceutical compositions containing them, their use and methods of preparation
DE10350717A1 (en) * 2003-10-30 2005-06-02 Boehringer Ingelheim Pharma Gmbh & Co. Kg Use of tyrosine kinase inhibitors for the treatment of inflammatory processes
GB0326459D0 (en) 2003-11-13 2003-12-17 Astrazeneca Ab Quinazoline derivatives
JP5032851B2 (en) 2004-02-03 2012-09-26 アストラゼネカ アクチボラグ Quinazoline derivatives
US20060035893A1 (en) 2004-08-07 2006-02-16 Boehringer Ingelheim International Gmbh Pharmaceutical compositions for treatment of respiratory and gastrointestinal disorders
PE20060777A1 (en) 2004-12-24 2006-10-06 Boehringer Ingelheim Int INDOLINONE DERIVATIVES FOR THE TREATMENT OR PREVENTION OF FIBROTIC DISEASES
CA2592900A1 (en) 2005-01-03 2006-07-13 Myriad Genetics Inc. Nitrogen containing bicyclic compounds and therapeutical use thereof
US8258145B2 (en) 2005-01-03 2012-09-04 Myrexis, Inc. Method of treating brain cancer
CA2833706C (en) 2005-11-11 2014-10-21 Boehringer Ingelheim International Gmbh Quinazoline derivatives for the treatment of cancer diseases
US7977346B2 (en) * 2006-01-17 2011-07-12 Guoqing Paul Chen Spiro compounds and methods of use
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AU2007299080B2 (en) 2006-09-18 2013-04-18 Boehringer Ingelheim International Gmbh Method for treating cancer harboring EGFR mutations
EP1921070A1 (en) 2006-11-10 2008-05-14 Boehringer Ingelheim Pharma GmbH & Co. KG Bicyclic heterocycles, medicaments comprising them, their use and process for their preparation
EP2118075A1 (en) 2007-02-06 2009-11-18 Boehringer Ingelheim International GmbH Bicyclic heterocycles, drugs containing said compounds, use thereof, and method for production thereof
WO2009057139A2 (en) 2007-10-29 2009-05-07 Natco Pharma Limited Novel 4-(tetrazol-5-yl)-quinazoline derivatives as anti cancer agents
CA2711582A1 (en) 2008-02-07 2009-08-13 Boehringer Ingelheim International Gmbh Spirocyclic heterocycles, formulations containing said compounds, use thereof and processes for the preparation thereof
CA2733153C (en) 2008-08-08 2016-11-08 Boehringer Ingelheim International Gmbh Cyclohexyloxy substituted heterocycles, pharmaceutical compositions containing these compounds and processes for preparing them
PL2451445T3 (en) 2009-07-06 2019-09-30 Boehringer Ingelheim International Gmbh Process for drying of bibw2992, of its salts and of solid pharmaceutical formulations comprising this active ingredient
TWI577671B (en) * 2011-11-14 2017-04-11 Sunshine Lake Pharma Co Ltd Aminoquinazoline derivatives and salts thereof and methods of use thereof
CN103172641B (en) * 2011-12-20 2014-06-11 钱卫 Heterocyclic amino and alkoxy-replaced quinazoline derivative and application thereof
JP6669499B2 (en) 2013-02-15 2020-03-18 カラ ファーマシューティカルズ インコーポレイテッド Therapeutic compounds
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JP2016510000A (en) 2013-02-20 2016-04-04 カラ ファーマシューティカルズ インコーポレイテッド Therapeutic compounds and uses thereof
RU2016112013A (en) * 2013-09-19 2017-10-24 Пьер Фабр Медикамент Quinazoline derivatives and their use as DNA methyltransferase inhibitors
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US9890173B2 (en) 2013-11-01 2018-02-13 Kala Pharmaceuticals, Inc. Crystalline forms of therapeutic compounds and uses thereof
US9242965B2 (en) 2013-12-31 2016-01-26 Boehringer Ingelheim International Gmbh Process for the manufacture of (E)-4-N,N-dialkylamino crotonic acid in HX salt form and use thereof for synthesis of EGFR tyrosine kinase inhibitors
CN105294716B (en) * 2015-11-18 2017-12-22 乳源瑶族自治县大众药品贸易有限公司 Two salicylates and its crystal formation of a kind of amino quinazoline derivative
CN105461729B (en) * 2015-11-18 2017-12-05 乳源瑶族自治县大众药品贸易有限公司 A kind of salt of EGFR inhibitor, crystal formation and application thereof
KR20190051010A (en) 2016-09-08 2019-05-14 칼라 파마슈티컬스, 인크. Crystalline Forms of Therapeutic Compounds and Their Uses
AU2017324713B2 (en) 2016-09-08 2020-08-13 KALA BIO, Inc. Crystalline forms of therapeutic compounds and uses thereof
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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8399667B2 (en) 2002-03-28 2013-03-19 Astrazeneca Ab 4-anilino quinazoline derivatives as antiproliferative agents
US8318752B2 (en) 2003-09-19 2012-11-27 Astrazeneca Ab 4-(3-chloro-2-fluoroanilino)-7-methoxy-6-{[1-(N-methylcarbamoyl-methyl)piperidin-4-yl]oxy}quinazoline, its pharmaceutically acceptable salts, and pharmaceutical compositions comprising the same
US8735410B2 (en) 2005-02-26 2014-05-27 Astrazeneca Ab Quinazoline derivatives as tyrosine kinase inhibitors
US8088782B2 (en) 2008-05-13 2012-01-03 Astrazeneca Ab Crystalline 4-(3-chloro-2-fluoroanilino)-7 methoxy-6-{[1-(N-methylcarbamoylmethyl)piperidin-4-yl]oxy}quinazoline difumarate form A
US8404839B2 (en) 2008-05-13 2013-03-26 Astrazeneca Ab Crystalline 4-(3-chloro-2-fluoroanilino)-7 methoxy-6-{[1-(N-methylcarbamoylmethyl)piperidin-4-yl]oxy} quinazoline difumarate Form A

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Publication number Publication date
MXPA03001725A (en) 2004-12-06
CA2417652C (en) 2008-10-28
EP1315718A1 (en) 2003-06-04
AU2001295481A1 (en) 2002-03-13
JP4901055B2 (en) 2012-03-21
ES2296812T3 (en) 2008-05-01
DE50113328D1 (en) 2008-01-10
DE10042059A1 (en) 2002-03-07
WO2002018372A1 (en) 2002-03-07
EP1315718B1 (en) 2007-11-28
JP2004507535A (en) 2004-03-11

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