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

J Med Chem. 1992 Nov 13;35(23):4384-92. doi: 10.1021/jm00101a016.


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.

MeSH terms

  • Animals
  • Anticholesteremic Agents / chemical synthesis*
  • Anticholesteremic Agents / chemistry
  • Anticholesteremic Agents / pharmacology
  • Imidazoles / chemical synthesis*
  • Imidazoles / chemistry
  • Imidazoles / pharmacology
  • Male
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Sterol O-Acyltransferase / antagonists & inhibitors*
  • Structure-Activity Relationship


  • Anticholesteremic Agents
  • Imidazoles
  • Sterol O-Acyltransferase