Selective thromboxane synthetase inhibitors. 3. 1H-imidazol-1-yl-substituted benzo[b]furan-, benzo[b]thiophene-, and indole-2- and -3-carboxylic acids.
The preparation of a series of 1H-imidazol-1-yl-substituted benzo[b]furan-, benzo[b]thiophene-, and indolecarboxylic acids is described. Most of the compounds were potent inhibitors of TxA2 synthetase in vitro, and the distance between the imidazole and carboxylic acid groups was found to be important for optimal potency. The most potent compound in vivo was 6-(1H-imidazol-1-ylmethyl)-3-methylbenzo[b]thiophene-2-carboxylic acid (71), which, in conscious dogs, showed a similar profile of activity to that of dazoxiben (1).
D000818:Animals; D001572:Benzofurans / Q000494:pharmacology*; D002264:Carboxylic Acids / Q000494:pharmacology*; D055598:Chemical Phenomena; D002621:Chemistry; D004285:Dogs; D007093:Imidazoles / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000494:pharmacology*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors* / Q000097:blood
D001572:Benzofurans; D002264:Carboxylic Acids; D007093:Imidazoles; D007211:Indoles; D013876:Thiophenes; D013930:Thromboxane-A Synthase