Synthesis and antisecretory and antiulcer activities of derivatives and analogues of 2-(2-pyridyl)tetrahydrothiophene-2-carbothioamide.
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.
D000818:Animals; D000897:Anti-Ulcer Agents / Q000138:chemical synthesis*; D005260:Female; D005750:Gastric Juice / Q000187:drug effects / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology; D007202:Indicators and Reagents; D008297:Male; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains; D013276:Stomach Ulcer / Q000517:prevention & control*; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use
D000897:Anti-Ulcer Agents; D007202:Indicators and Reagents; D011725:Pyridines; D013876:Thiophenes; D006632:Histamine