Pharmacology
New benzyl benzamide compound inhibits CETP by 82.2% in vitro, with docking confirming it fits the drug pocket (Arch Pharm 2017)
Original title: Synthesis, Biological Evaluation, and Molecular Modeling Study of Substituted Benzyl Benzamides as CETP Inhibitors
Ten substituted benzyl benzamide compounds (8a-j) were synthesised and characterised as candidate CETP inhibitors. In vitro CETP inhibition assays found compound 8j the most active, with 82.2% inhibition at 10 uM and an IC50 of 1.3 uM. Molecular docking showed the compounds fit within the CETP binding cleft, surrounded by a hydrophobic lining, and the shared scaffold of the series matched known CETP inhibitor pharmacophoric points, particularly its hydrophobic and aromatic features. An early-stage medicinal chemistry discovery paper with in vitro enzyme data, no animal or clinical testing.
Original abstract
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.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.