Selective thromboxane synthetase inhibitors. 1. 1-[(Aryloxy)alkyl]-1H-imidazoles
- 1 October 1985
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 28 (10), 1427-1432
- https://doi.org/10.1021/jm00148a009
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 enzymes 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 .ANG. 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 acie (14).This publication has 20 references indexed in Scilit:
- Steric factors in the inhibitory interaction of imidazoles with microsomal enzymesBiochemical Pharmacology, 1977
- Application of imidazole as a selective inhibitor thromboxane synthetase in human platelets.Proceedings of the National Academy of Sciences, 1977
- : A selective inhibitor of thromboxane synthetaseProstaglandins, 1977
- Prostacyclin (PGX) is the endogeneous metabolite responsible for relaxation of coronary arteries induced by arachidonic acidProstaglandins, 1977
- HUMAN ARTERIAL AND VENOUS TISSUES GENERATE PROSTACYCLIN (PROSTAGLANDIN X), A POTENT INHIBITOR OF PLATELET AGGREGATIONThe Lancet, 1977
- Arterial walls generate from prostaglandin endoperoxides a substance (prostaglandin X) which relaxes strips of mesenteric and coeliac arteries and inhibits platelet aggregationProstaglandins, 1976
- A lipid peroxide inhibits the enzyme in blood vessel microsomes that generates from prostaglandin endoperoxides the substance (prostaglandin X) which prevents platelet aggregationProstaglandins, 1976
- Arterial walls are protected against deposition of platelet thrombi by a substance (prostaglandin X) which they make from prostaglandin endoperoxidesProstaglandins, 1976
- An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregationNature, 1976
- Identification of an enzyme in platelet microsomes which generates thromboxane A2 from prostaglandin endoperoxidesNature, 1976