Discovery of hydroxyl 1,2-diphenylethanamine analogs as potent cholesterol ester transfer protein inhibitors

Bioorg Med Chem Lett. 2016 Jul 15;26(14):3278-3281. doi: 10.1016/j.bmcl.2016.05.058. Epub 2016 May 20.

Abstract

Hydroxyl 1,2-diphenylethanamine analogs were identified as potent inhibitors of cholesterol ester transfer protein (CETP), a therapeutic target to raise HDL cholesterol. In an effort to improve the pharmaceutical properties in the previously disclosed DiPhenylPyridineEthanamine (DPPE) series, polar groups were introduced to the N-linked quaternary center. Optimization of analogues for potency, in vitro liability profile and efficacy led to identification of lead compound 16 which demonstrated robust pharmacodynamic effects in human CETP/apo-B100 dual transgenic mice.

Keywords: CETP inhibitors; HDL cholesterol; Hydroxyl 1,2-diphenylethanamine.

MeSH terms

  • Amines / chemical synthesis
  • Amines / chemistry
  • Amines / pharmacology*
  • Animals
  • Cholesterol Ester Transfer Proteins / antagonists & inhibitors*
  • Cholesterol Ester Transfer Proteins / metabolism
  • Dose-Response Relationship, Drug
  • Drug Discovery*
  • Humans
  • Mice
  • Mice, Transgenic
  • Molecular Structure
  • Structure-Activity Relationship

Substances

  • Amines
  • Cholesterol Ester Transfer Proteins