Selective thromboxane synthetase inhibitors. 4. 2-(1H-imidazol-1-ylmethyl) carboxylic acids of benzo[b]furan, benzo[b]thiophene, indole, and naphthalene.
The preparation of a series of 2-(1H-imidazol-1-ylmethyl)-substituted carboxylic acids of benzo[b]furan, benzo-[b]thiophene, indole, and naphthalene is described. All compounds showed a similar level of activity as TxA2 synthetase inhibitors in vitro, having IC50 values between 1 and 7 X 10(-8) M. In the cases examined, compounds had, at most, only negligible activity against PGI2 synthetase, cyclooxygenase, and steroid 11 beta-hydroxylase. The benzo[b]thiophenes generally showed the greatest potency in vivo, and compounds 72, 73, and 75 caused almost complete inhibition of thromboxane production for 6 h after oral administration of 0.5 mg/kg to conscious dogs. In the case of 73 and 75, thromboxane production was still inhibited by 80% after 24 h.
D000818:Animals; D001572:Benzofurans / Q000494:pharmacology*; D002264:Carboxylic Acids / Q000494:pharmacology*; D055598:Chemical Phenomena; D002621:Chemistry; D016861:Cyclooxygenase Inhibitors; D003577:Cytochrome P-450 Enzyme System; D004285:Dogs; D011464:Epoprostenol / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D007093:Imidazoles / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D019746:Intramolecular Oxidoreductases; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology; D051381:Rats; D013252:Steroid 11-beta-Hydroxylase / Q000037:antagonists & inhibitors; D013876:Thiophenes / Q000494:pharmacology*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors* / Q000097:blood
D001572:Benzofurans; D002264:Carboxylic Acids; D016861:Cyclooxygenase Inhibitors; D007093:Imidazoles; D007211:Indoles; D009281:Naphthalenes; D013876:Thiophenes; D003577:Cytochrome P-450 Enzyme System; D011464:Epoprostenol; D013252:Steroid 11-beta-Hydroxylase; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase; D013930:Thromboxane-A Synthase