Pharmacophore-based design,synthesis,and biological evaluation of novel 3-((3,4-dichlorophenyl)(4-substituted benzyl)amino)propanamides as cholesteryl ester transfer protein(CETP)inhibitors

摘要

Cholesteryl ester transfer protein(CETP) is a plasma glycoprotein that plays an important role in decreasing high-density lipoprotein cholesterol(HDL-C) levels and increasing low-density lipoprotein cholesterol(LDL-C) levels.Inhibition of CETP may be a new therapy for treating atherosclerosis.Herein,we report the development of a ligand-based pharmacophore model and pharmacophore-based virtual screening of the ZINC/big-n-greasy database,leading to the identification of compound H-10 as a potential CETP inhibitor in vitro.Based on H-10,a series of 3-((3,4-dichlorophenyl)(4-substituted benzyl)amino) propanamides were designed,synthesized,and evaluated against CETP.Compound 41was found to have the best activity,resulting in 85.0%inhibition of CETP at 10 μmol/L.