Selective thromboxane synthetase inhibitors. 4. 2-(1H-Imidazol-1-ylmethyl)benzo[b]furan-, -benzo[b]thiophene-, -indole- and -naphthalenecarboxylic acids
- 1 September 1986
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 29 (9) , 1643-1650
- https://doi.org/10.1021/jm00159a013
Abstract
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 .times. 10-8 M. In the cases examined, compounds had, at most, only negligible activity against PGI2 synthetase, cyclooxygenase, and steroid 11.beta.-hydroxlase. The benzo[b]thiopenes generally showed the greatest potency in vivo, and compounds 72, 73, and 75 caused almost complete inhibition of thromboxane production for 6 hr 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.This publication has 6 references indexed in Scilit:
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