Design, Synthesis and Biological Evaluation of N,N-Substituted Amine Derivatives as Cholesteryl Ester Transfer Protein Inhibitors

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 mu M) in vitro. Furthermore, compound 17 was selected for an in vitro metabolic stability study.