SU751007A1 - 2-[n-[4-(3,3-dimethyltriazeno)-benzenesulfonyl]amido]-4,6-dimethypyrimidine displaying anti-inflammatory activity - Google Patents

Abstract

2-{N- 4-

Description

The invention relates to the synthesis of a new compound 2-H-4-(3,3-dimethyltriazeno)-benzenesulfonate-amideC 4 , 6-dimethylpyrimidine, which exhibits anti-inflammatory action and can be used in medicine.

Triazene derivatives are known to have anti-inflammatory action.

Butadiene, which has anti-inflammatory action L2J, is widely used in medical practice.

However, butadion is toxic and also has a side effect: it irritates the gastric mucosa,

The aim of the present invention is to expand the arsenal of means of influencing a living organism and having an anti-inflammatory effect.

The stated goal is achieved by the described 2-Hy-4-(3,3-dimethyltriazeno)benzenesulfonyl G|-amid-4,6-dimethylpyrimidine, which exhibits anti-inflammatory action of the formula:

HjN SOjNftfJ (SN,)gM-No.

7) 1007

.CHj

y„.

R:Hj)zH-N-N-r SO HH

The proposed substance was synthesized by the known pj method according to the following scheme:

Example, 27.8 g (0.1 mol) of sulfadimidine are mixed with 50 ml of water and 25 ml of concentrated HCl. Maintaining the temperature at 0-2°C, 6.9 g (0.1 mol) are added dropwise.

HaNOu dissolved in 50 ml of water, and the reaction mixture is stirred for 0.5 hour. 28 g (0.1 mol) of dimethylaniline hydrochloride dissolved in 200 ml of water are added to the resulting solution and neutralized with a concentrated NaOH solution to pH 7-8. The precipitated product is filtered, washed with water, dried and crystallized from alcohol. 25 g (80.83%) of 2-{3-(3,3-dimethyltriazeno)benzenesulfonyl-1-amido-4,6-dimethylpyrimidine with a melting point of 193-195°C are obtained.

Spectrum PNR m.d., ); CHg 2.23

(СНз,)Н 3.21; 3.51; CH 6.70;

S.E.

,47, 7,99.

Found (%): C 50.37; H 5.24; N25.10; S 9.81;

C,4N18Nbog

Calculated (%); C 50.29; H 5.43;

N 25.13; S 9.59.

Biological activity tests were conducted on mongrel white mice and rats. The toxicity of the compound was determined on healthy white mice, and the anti-inflammatory activity was determined on male rats weighing 180-260 g, in which adjuvant arthritis was reproduced by introducing 0.1 ml of Freund's adjuvant into the left back paw. Treatment of the animals began on the 3rd day of reproduction of the inflammatory process. The drug was administered as a suspension in 1% starch paste intragastrically with the help of a gastroenterologist. Treatment was carried out daily, except for weekends, for 17 days.

(12 injections in total). The control group of rats similarly received 1% starch paste. A total of 20 animals were used in the experiment. During the experiment, the dynamics of the rats' body weight and joint swelling were monitored (swelling was determined by the volume of displaced water when the swollen limb was immersed in a graduated test tube). The percentage deviation of limb swelling from the control was calculated using the formula:

X 100, where

% deviation

Oh

0., - moderate joint swelling

V

control group, 0 - average swelling of joints

experimental animals. The percentage of deviation from control of other indicators was calculated similarly.

The results of biological tests and the structural formula of the compound are presented in Table 1, which also contains the data obtained in

in a similar experiment, where a well-known anti-inflammatory drug, butadion, was used to treat rats. The table shows that the proposed compound reduces swelling

joints of rats with adjuvant arthritis throughout the experiment; in the second half of the experiment, the anti-inflammatory activity is very pronounced, differences

0 reliable. The compound has no effect on the general condition of the animals, body weight, liver. The weight of the spleen and the activity indicators of the process in the experimental group are significantly lower.

5 control (P CO,001).

Compared with butadione, (3,3-diethyltriazeno) benzene sulfonyl-1-amino-4,6-dimethylpyrimidine is less toxic, has a more pronounced anti-inflammatory effect751007

has a stronger effect and has a more pronounced immunosuppressive activity.

Table

Claims (1)

2-{N-[4-(3,3-DIMETHYLTRIAZENO)-benzenesulfonyl3-amido]-4,6-DIMETHYLPYRIMIDINE of formula (CH ₃ ) ₂ NN=N-Qh 3 exhibiting anti-inflammatory action.