Thromboxane synthetase inhibitors and antihypertensive agents. 1. N-[(1H-imidazol-1-yl)alkyl]aryl amides and N-[(1H-1,2,4-triazol-1-yl)alkyl]aryl amides.
The title compounds were prepared to investigate their potential as thromboxane synthetase inhibitors as well as antihypertensive agents. Imidazoles VIII and triazoles X were prepared to examine the effects of aromatic substitution, chain length, and heterocycle substitution upon biological activity. Imidazoles VIII and triazoles X were thromboxane synthetase inhibitors that did not inhibit prostacyclin formation. The most interesting thromboxane synthetase inhibitors prepared were 4-chloro-, 4-(trifluoromethyl)-, and 4-bromobenzamide derivatives of (1H-imidazol-1-yl)alkylamines with C5-C8 alkyl chains separating the heterocycle from the amide moiety, while the most active antihypertensive agents were 3- or 4-chloro-, -bromo, or -(trifluoromethyl)benzamides with C3 alkyl chains. The best thromboxane synthetase inhibitors in this study were up to 10 times more potent than the standard, dazoxiben (UK 37,248).
D000577:Amides / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D013329:Structure-Activity Relationship; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology
D000577:Amides; D000959:Antihypertensive Agents; D007093:Imidazoles; D014230:Triazoles; D013930:Thromboxane-A Synthase