Design and synthesis of new tetrahydroquinolines derivatives as CETP inhibitors

Bioorg Med Chem Lett. 2012 Jun 1;22(11):3671-5. doi: 10.1016/j.bmcl.2012.04.042. Epub 2012 Apr 13.

Abstract

This letter describes the discovery and SAR optimization of tetrazoyl tetrahydroquinoline derivatives as potent CETP inhibitors. Compound 6m exhibited robust HDL-c increase in hCETP/hApoA1 double transgenic model and favorable pharmacokinetic properties.

MeSH terms

  • Animals
  • Apolipoprotein A-I / genetics
  • Apolipoprotein A-I / metabolism
  • Cholesterol Ester Transfer Proteins / antagonists & inhibitors*
  • Cholesterol Ester Transfer Proteins / genetics
  • Cholesterol Ester Transfer Proteins / metabolism
  • Cholesterol, HDL / drug effects
  • Cholesterol, HDL / metabolism
  • Dogs
  • Drug Design*
  • Female
  • Hypolipidemic Agents / chemical synthesis*
  • Hypolipidemic Agents / chemistry
  • Hypolipidemic Agents / pharmacokinetics
  • Injections, Intravenous
  • Male
  • Mice
  • Mice, Transgenic
  • Quinolines / chemical synthesis
  • Quinolines / chemistry*
  • Quinolines / pharmacokinetics
  • Rats
  • Rats, Sprague-Dawley
  • Structure-Activity Relationship
  • Tetrazoles / chemical synthesis*
  • Tetrazoles / chemistry
  • Tetrazoles / pharmacokinetics

Substances

  • Apolipoprotein A-I
  • Cholesterol Ester Transfer Proteins
  • Cholesterol, HDL
  • Hypolipidemic Agents
  • Quinolines
  • Tetrazoles
  • 1,2,3,4-tetrahydroquinoline