Acyl-CoA: cholesterol O-acyl transferase (ACAT) inhibitors. 1. 2-(Alkylthio)-4,5-diphenyl-1H-imidazoles as potent inhibitors of ACAT

Citations Over TimeTop 10% of 1992 papers

Abstract

A potent, bioavailable ACAT inhibitor may have beneficial effects in the treatment of atherosclerosis by (i) reducing the absorption of dietary cholesterol, (ii) reducing the secretion of very low density lipoproteins into plasma from the liver, and (iii) preventing the transformation of arterial macrophages into foam cells. We have found that a mevalonate derivative 2, which contains a 4,5-diphenyl-1H-imidazol-2-yl moiety, inhibits rat hepatic microsomal ACAT in vitro and produces a significant hypocholesterolemic effect in the cholesterol-fed rat. Structure-activity relationships for analogues of 2 demonstrate that the 4,5-diphenyl-1H-imidazole moiety is a pharmacophore for inhibition of rat microsomal ACAT.

Related Papers

• → Quantitation of the Pool of Cholesterol Associated with Acyl-CoA:Cholesterol Acyltransferase in Human Fibroblasts(1997)115 cited
• → Evidence that lecithin: Cholesterol acyltransferase acts on both high-density and low-density lipoproteins(1983)29 cited
• → The effect of feeding and fasting on the activity of acyl‐CoA:cholesterol acyltransferase in rat small intestine(1982)25 cited
• → Fatty acyl CoA synthetase activity in normal and atherosclerotic rabbit aortic tissue(1975)4 cited