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-β-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.