Cholesteryl ester transfer protein inhibitory oxoacetamido-benzamide derivatives: Glide docking, pharmacophore mapping, and synthesis

Dyslipidemia is an abnormal lipid profile associated with many common diseases, including coronary heart disease and atherosclerosis. Cholesteryl ester transfer protein (CETP) a hydrophobic plasma glycoprotein that responsible for the of cholesteryl from high-density lipoprotein athero-protective particles to pro-atherogenic very low-density particles. The requirement new CETP inhibitors, which block this process has driven our current work. Here, synthesis as well ligand-based structure-based design seven oxoacetamido-benzamides 9a-g inhibitory activity described. An in vitro study demonstrated most these compounds have appreciable activity. Compound 9g showed highest against IC50 0.96 μM. Glide docking data torcetrapib provide evidence they are accommodated active site where interactions drive ligand/CETP complex formation. Furthermore, match features known providing rationale their high scores binding domain. Therefore, show potential use novel inhibitors.