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.
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.
Larsen
S D
SD
Metabolic Diseases Research, Upjohn Company, Kalamazoo, Michigan 49001.
Spilman
C H
CH
Bell
F P
FP
Dinh
D M
DM
Martinborough
E
E
Wilson
G J
GJ
D000818:Animals; D000924:Anticholesteremic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D008297:Male; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D000924:Anticholesteremic Agents; D011744:Pyrimidinones; D002784:Cholesterol; D002785:Sterol O-Acyltransferase