Design, synthesis and structure-activity-relationship of 1,5-tetrahydronaphthyridines as CETP inhibitors

Bioorg Med Chem Lett. 2012 May 1;22(9):3056-62. doi: 10.1016/j.bmcl.2012.03.075. Epub 2012 Mar 28.

Abstract

This Letter describes the discovery and SAR optimization of 1,5-tetrahydronaphthyridines, a new class of potent CETP inhibitors. The effort led to the identification of 21b and 21d with in vitro human plasma CETP inhibitory activity in the nanomolar range (IC(50)=23 and 22nM, respectively). Both 21b and 21d exhibited robust HDL-c increase in hCETP/hApoA1 dual heterozygous mice model.

MeSH terms

  • Animals
  • Cholesterol Ester Transfer Proteins / antagonists & inhibitors*
  • Cholesterol, HDL
  • Dose-Response Relationship, Drug
  • Drug Design
  • Humans
  • Inhibitory Concentration 50
  • Mice
  • Naphthyridines / chemical synthesis
  • Naphthyridines / pharmacology*
  • Structure-Activity Relationship

Substances

  • Cholesterol Ester Transfer Proteins
  • Cholesterol, HDL
  • Naphthyridines