rp-40749 and Stomach-Ulcer

New thioamide derivatives of 2-(2-pyridyl)tetrahydrothiophene-2-carbothioamide (29) and related compounds (in which the tetrahydrothiophene ring was replaced by tetrahydrothiopyran, tetrahydrofuran, 1,3-dithiane, or 1,3-oxathiane and where the pyridine ring was replaced by other nitrogen heterocycles) were synthesized and tested for their antisecretory and antiulcer activities. These thioamides were prepared according to one of the following methods: reaction of an isothiocyanate with the carbanion of the corresponding cyclic precursor (for secondary thioamides); reaction of ammonia or an amine with the dithio ester prepared from the same precursor (for primary, secondary, and tertiary thioamides). These thioamides were evaluated by the Shay method to measure their antisecretory activity and by the stress-induced-ulcer method to test their antiulcer activity. Structure-activity relationships are discussed. N-Methyl-2-(2-pyridyl)tetrahydrothiophene-2-carbothioamide (R.P. 40749, 30) exhibited activities that were at least 10 times higher than those reported for cimetidine.

Topics: Animals; Anti-Ulcer Agents; Female; Gastric Juice; Histamine; Indicators and Reagents; Male; Pyridines; Rats; Rats, Inbred Strains; Stomach Ulcer; Structure-Activity Relationship; Thiophenes

The antisecretory and antiulcerogenic effects of R.P. 40,749 were estimated in Shay Rats; for comparison, the cimetidine effects were simultaneously studied. Results demonstrated that R.P. 40,749 had potent antisecretory and antiulcerogenic effects which were, at least, 10 times more pronounced than those of cimetidine. The mechanism of action of R.P. 40,749 has not yet been determined but it seems that an anticholinergic or an H2 receptor antagonist effect should be excluded.

Topics: Animals; Anti-Ulcer Agents; Cimetidine; Female; Gastric Juice; Rats; Stomach Ulcer; Thiophenes