150423-87-3Relevant articles and documents
Inhibitors of acyl-CoA:cholesterol acyltransferase. 5. Identification and structure-activity relationships of novel β-ketoamides as hypocholesterolemic agents
Augelli-Szafran,Blankley,Roth,Trivedi,Bousley,Essenburg,Hamelehle,Krause,Stanfield
, p. 2943 - 2949 (2007/10/02)
A study of structure-activity relationships of substituted β-ketoamide ACAT inhibitors I and II was performed. The results of this study suggest that whereas the β-keto group was tolerated with no loss in activity, β- hydroxy and oxime moieties led to significantly reduced activity in vitro and in vivo. The most potent inhibitor from the acyclic series (I) (11, IC50 = 0.006 μM) contained a C-13 alkyl chain. This compound reduced plasma total cholesterol by 38% and 66% at 3 and 30 mg/kg, respectively, in cholesterol- fed rats. Dimethylation α to the anilide core (5) and subsequent N- methylation of the amide NH (6) decreased in vitro potency significantly. It was also found that high potency was retained with inhibitors which incorporated the carbonyl into a lactam ring (II).
