Synthesis and hypocholesterolemic activity of 6,7-dihydro-4H-pyrazolo[1,5-a]pyrrolo[3,4-d]pyrimidine-5,8-diones, novel inhibitors of acylCoA:cholesterol O-acyltransferase

J Med Chem. 1991 May;34(5):1721-7. doi: 10.1021/jm00109a028.

Abstract

A novel series of 6,7-dihydro-4H-pyrazolo[1,5-a]pyrrolo[3,4-d]pyrimidine-5,8-dione inhibitors of the enzyme acyl-CoA:cholesterol O-acyltransferase is described. A number of these derivatives were found to be potent modulators of serum lipoprotein levels in cholesterol-fed rats. Further evaluation of one of the most effective analogues confirmed that it was significantly blocking the absorption of cholesterol from the gut.

MeSH terms

  • Animals
  • Anticholesteremic Agents / chemical synthesis*
  • Anticholesteremic Agents / pharmacology
  • Chemical Phenomena
  • Chemistry
  • Cholesterol / blood
  • Cholesterol / metabolism
  • Male
  • Pyrimidinones / chemical synthesis*
  • Pyrimidinones / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Sterol O-Acyltransferase / antagonists & inhibitors*
  • Structure-Activity Relationship

Substances

  • Anticholesteremic Agents
  • Pyrimidinones
  • Cholesterol
  • Sterol O-Acyltransferase