The class
Bis(trifluoromethyl) benzylamino benzamides identified as potent new CETP inhibitor lead compounds (Med Chem 2022)
Original title: Synthesis and Molecular Modeling of Novel 3,5-Bis(trifluoromethyl) benzylamino Benzamides as Potential CETP Inhibitors
Researchers synthesised eight 3,5-bis(trifluoromethyl)benzylamino benzamide compounds (9a-d and 10a-d) and tested their ability to inhibit cholesteryl ester transfer protein (CETP), which moves cholesteryl ester and phospholipids from atheroprotective HDL to proatherogenic LDL and VLDL. In vitro testing showed inhibitory activity ranging from 42.2 to 100 percent at 10 micromolar concentration, with the unsubstituted compound 9a and the ortho-trifluoromethyl-substituted 9b the most effective, reaching IC50 values of 1.36 and 0.69 micromolar respectively. High docking scores against the CETP structure 4EWS and pharmacophore mapping consistent with known CETP inhibitor features support their binding at the CETP active site. The authors conclude this benzamide series can serve as a promising CETP inhibitor lead for further development.
Original abstract
Background: There is an alarming spread of cases of lipid disorders in the world that occur due to harmful lifestyle habits, hereditary risk influences, or as a result of other illnesses or medicines. Cholesteryl Ester Transfer Protein (CETP) is a 476-residue lipophilic glycoprotein that helps in the transport of cholesteryl ester and phospholipids from the atheroprotective HDL to the proatherogenic LDL and VLDL. Inhibition of CETP leads to elevation of HDL cholesterol and reduction of LDL cholesterol and triglycerides; therefore, it is considered a good target for the treatment of hyperlipidemia and its comorbidities.
Objective: In this research, synthesis, characterization, molecular modeling, and biological evaluation of eight 3,5-bis(trifluoromethyl)benzylamino benzamides 9a-d and 10a-d were carried out.
Methods: The synthesized molecules were characterized using 1H-NMR, 13C-NMR, IR, and HR-MS. They were biologically tested in vitro to estimate their CETP inhibitory activity.
Results: These compounds offered inhibitory effectiveness ranging from 42.2% to 100% at a concentration of 10 μM. Compounds bearing unsubstituted three aromatic rings (9a) or ortho-CF3 substituted (9b) were the most effective compounds among their analogs and showed IC50 values of 1.36 and 0.69 μM, respectively. The high docking scores of 9a-d and 10a-d against 4EWS imply that they might be possible CETP inhibitors. Pharmacophore mapping results demonstrate that the series approves the fingerprint of CETP active inhibitors and therefore explains their high binding affinity against CETP binding site.
Conclusion: This work concludes that 3,5-bis(trifluoromethyl)benzylamino benzamides can serve as a promising CETP inhibitor lead compound.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.