Selective thromboxane synthetase inhibitors. 1. 1-[(Aryloxy)alkyl]-1H-imidazoles.

Article Details

Citation

Cross PE, Dickinson RP, Parry MJ, Randall MJ

Selective thromboxane synthetase inhibitors. 1. 1-[(Aryloxy)alkyl]-1H-imidazoles.

J Med Chem. 1985 Oct;28(10):1427-32.

PubMed ID
3930740 [ View in PubMed
]
Abstract

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 11 beta-hydroxylase. The preparation of a series of analogues is described, and activity against TxA2 synthetase, PGI2 synthetase, cyclooxygenase, and steroid 11 beta-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 A 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 11 beta-hydroxylase. The most potent and selective compound was found to be 4-[2-(1H-imidazol-1-yl) ethoxy]benzoic acid (14).

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
DazoxibenThromboxane-A synthaseIC 50 (nM)3N/AN/ADetails