STUDIES ON ANTIULCER DRUGS .7. 2-GUANIDINO-4-PYRIDYLTHIAZOLES AS HISTAMINE H-2-RECEPTOR ANTAGONISTS WITH POTENT GASTROPROTECTIVE EFFECTS AGAINST NONSTEROIDAL ANTIINFLAMMATORY DRUG-INDUCED INJURY

A series of 2-guanidino-4-pyridylthiazole derivatives were synthesized and evaluated for anti-aspirin-ulcer, gastric antisecretory, and hist amine-H-2-receptor-antagonist activities. Several compounds showed sup erior anti-aspirin-ulcer activity to that of clinically used H-2-antag onists in the rat. Among them, (acetamidomethyl)pyridin-2-yl]-2-guanid inothiazole (8) demonstrated potent inhibitory activities against gast ric lesions caused by two kinds of nonsteroidal antiinflammatory drugs , aspirin and indomethacin, respectively, in addition to strong antise cretory activity. Compound 8 possessed a preventable ability for the a spirin-induced reduction of the gastric mucosal blood flow at an intra gastric administration of 32 mg/kg in the rat. On the other hand, famo tidine (32 mg/kg) exhibited no significant effect and ranitidine (100 mg/kg) aggravated the blood flow in this system.