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

Molecules. 2017 Oct 3;22(10):1658. doi: 10.3390/molecules22101658.

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.

Keywords: CETP inhibitors; HDL-C; N,N-substituted amine derivatives; synthesis.

MeSH terms

  • Amines / chemical synthesis
  • Amines / chemistry*
  • Amines / pharmacology
  • Cholesterol Ester Transfer Proteins / antagonists & inhibitors*
  • Drug Design
  • Humans
  • Microsomes, Liver
  • Structure-Activity Relationship

Substances

  • Amines
  • CETP protein, human
  • Cholesterol Ester Transfer Proteins