The class
N,N-substituted amine derivatives yield a sub-micromolar CETP inhibitor lead compound (Molecules 2017)
Original title: Design, Synthesis and Biological Evaluation of N,N-Substituted Amine Derivatives as Cholesteryl Ester Transfer Protein Inhibitors
Using a bioisosterism design strategy, researchers synthesised twenty-two N,N-substituted amine derivatives and evaluated their inhibitory activity against cholesteryl ester transfer protein (CETP). Structure-activity relationship studies showed hydrophilic groups at the 2-position of the tetrazole ring and 3,5-bistrifluoromethyl groups on the benzene ring were important contributors to potency. Compound 17 was the most potent, with an IC50 of 0.38 plus or minus 0.08 micromolar in vitro, and was selected for further in vitro metabolic stability testing. The results identify compound 17 as a promising lead for further CETP inhibitor development.
Original abstract
N,N-Substituted amine derivatives were designed by utilizing a bioisosterism strategy. Consequently, twenty-two compounds were synthesized and evaluated for their inhibitory activity against CETP. Structure-activity relationship (SAR) studies indicate that hydrophilic groups at the 2-position of the tetrazole and 3,5-bistrifluoromethyl groups on the benzene ring provide important contributions to the potency. Among these compounds, compound 17 exhibited excellent CETP inhibitory activity (IC50 = 0.38 ± 0.08 μM) in vitro. Furthermore, compound 17 was selected for an in vitro metabolic stability study.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.