Synthesis, Biological Evaluation, and Molecular Modeling Study of Substituted Benzyl Benzamides as CETP Inhibitors

Cardiovascular disease is the most common cause for mortality and morbidity in the developed world; its risk is inversely related to the high‐density lipoprotein (HDL) cholesterol levels. Therefore, there is a great interest in developing new cholesteryl ester transfer protein (CETP) inhibitors capable of raising HDL as a novel approach for the prevention of cardiovascular disease. Herein, the synthesis and characterization of ten benzyl benzamides 8a–j that aim at CETP inhibition was performed. The in vitro CETP inhibition bioassay revealed that benzamide 8j had the best activity, with a percent inhibition of 82.2% at 10 μM concentration and an IC50 value of 1.3 μM. The docking study shows that the verified compounds accommodate the binding cleft of CETP and are enclosed by a hydrophobic lining. Furthermore, the scaffold of 8a–j matches the pharmacophoric points of CETP inhibitors, particularly in its hydrophobic and aromatic functionalities. New cholesteryl ester transfer protein (CETP) inhibitors capable of raising the high‐density lipoprotein levels may be a novel approach for the prevention of cardiovascular disease. Ten new benzyl benzamides (8a–j) were characterized for their CETP inhibitory activities. The scaffold of 8a–j matches the pharmacophoric points of CETP inhibitors, particularly in its hydrophobic and aromatic functionalities.
Source: Archiv der Pharmazie - Category: Drugs & Pharmacology Authors: Tags: Full Paper Source Type: research