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

S D Larsen; C H Spilman; F P Bell; D M Dinh; E Martinborough; G J Wilson

doi:10.1021/jm00109a028

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.

Authors

S D Larsen¹, C H Spilman, F P Bell, D M Dinh, E Martinborough, G J Wilson

Affiliation

¹ Metabolic Diseases Research, Upjohn Company, Kalamazoo, Michigan 49001.

PMID: 2033594
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