Selective Thromboxane Synthetase Inhibitors. 1. 1--1H-imidazoles

Article abstract of DOI:10.1021/jm00148a009

1-(2-Phenoxyethyl)-1H-imidazole was found to be an inhibitor of thromboxane (TxA2) synthetase, but it also inhibited the adrenal cytochrome P-450 enzyme steroid 11β-hydroxylase.The preparation of a series of analogues is described, and activity against TxA2 synthetase, PGI2 synthetase, cyclooxygenase, and steroid 11β-hydroxylase is discussed.Potency against TxA2 synthetase was increased by introduction of a carboxyl group at a suitable distance from the imidazole ring.A distance of 8.1-8.8 Angstroem between N-1 of the imidazole and the carboxyl carbon was found to be optimal.Introduction of a carboxyl group also had the effect of reducing activity against steroid 11β-hydroxylase.The most potent and selective compound was found to be 4-<2-(1H-imidazol-1-yl)ethoxy>benzoic acid (14).