4-CF3-ezetimibe analogs: design, synthesis, and biological evaluation of cholesterol absorption inhibitions

On the purpose of looking for better cholesterol absorption inhibitors, several trifluoromethyl substituted ezetimibe analogs 1a-d were designed and synthesized. The key steps in the synthesis of these optically pure trans-4-CF3-beta-lactams include chiral auxiliary induced asymmetric hydrogenation and substrate controlled stereoselective alkylation. The inhibitory activities of these target compounds were evaluated on the cholesterol absorption in Caco-2 cells. The result showed that the inhibitory activity of compound 1a was comparable to ezetimibe. (C) 2013 Elsevier Ltd. All rights reserved.