Studies on antiulcer drugs. 7. 2-Guanidino-4-pyridylthiazoles as histamine H2-receptor antagonists with potent gastroprotective effects against nonsteroidal antiinflammatory drug-induced injury
作者:Yousuke Katsura、Yoshikazu Inoue、Tetsuo Tomishi、Hirohumi Ishikawa、Hisashi Takasugi
DOI:10.1021/jm00027a007
日期:1994.1
A series of 2-guanidino-4-pyridylthiazole derivatives were synthesized and evaluated for anti-aspirin-ulcer, gastric antisecretory, and histamine-H-2-receptor-antagonist activities. Several compounds showed superior anti-aspirin-ulcer activity to that of clinically used H-2-antagonists in the rat. Among them, 4-[6-(acetamidomethyl)pyridin-2-yl]-2-guanidinothiazole (8) demonstrated potent inhibitory activities against gastric lesions caused by two kinds of nonsteroidal antiinflammatory drugs, aspirin and indomethacin, respectively, in addition to strong antisecretory activity. Compound 8 possessed a preventable ability for the aspirin-induced reduction of the gastric mucosal blood flow at an intragastric administration of 32 mg/kg in the rat. On the other hand, famotidine (32 mg/kg) exhibited no significant effect and ranitidine (100 mg/kg) aggravated the blood flow in this system.