The class
Novel trifluoromethyl benzamides identified as potent CETP inhibitors with sub-micromolar activity (Curr Comput Aided Drug Des 2024)
Original title: Synthesis, Molecular Modeling and Biological Evaluation of Novel Trifluoromethyl Benzamides as Promising CETP Inhibitors
Researchers synthesised nine novel benzylamino benzamide compounds (8a-8f and 9a-9c) bearing a trifluoromethyl group and evaluated their ability to inhibit cholesteryl ester transfer protein (CETP), which relocates cholesterol esters from HDL to LDL. In vitro biological testing showed potential CETP inhibitory activity across the series, with compound 9c the most potent, reaching an IC50 of 1.03 micromolar. Induced-fit docking demonstrated that all nine compounds fit the CETP active site, with hydrophobic interactions predominating in ligand-CETP complex formation, and pharmacophore mapping confirmed the scaffold's CETP-inhibitor features underlying its high binding affinity.
Original abstract
Background: Hyperlipidemia is considered a major risk factor for the progress of atherosclerosis.
Objective: Cholesteryl ester transfer protein (CETP) facilitates the relocation of cholesterol esters from HDL to LDL. CETP inhibition produces higher HDL and lower LDL levels.
Methods: Synthesis of nine benzylamino benzamides 8a-8f and 9a-9c was performed.
Results: In vitro biological study displayed potential CETP inhibitory activity, where compound 9c had the best activity with an IC50 of 1.03 μM. Induced-fit docking demonstrated that 8a-8f and 9a-9c accommodated the CETP active site and hydrophobic interaction predominated ligand/ CETP complex formation.
Conclusion: Pharmacophore mapping showed that this scaffold endorsed CETP inhibitors features and consequently elaborated the high CETP binding affinity.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.