Peroxisome proliferator-activated receptor agonists with phenethylphenylphthalimide skeleton derived from thalidomide-related liver X receptor antagonists: relationship between absolute configuration and subtype selectivity

Bioorg Med Chem. 2011 May 15;19(10):3156-72. doi: 10.1016/j.bmc.2011.03.065. Epub 2011 Apr 3.

Abstract

Introduction of an alkylcarboxylic acid unit, which is a partial structure of endogenous peroxisome proliferator-activated receptor (PPAR) ligands, into a phenethylphenylphthalimide skeleton, which possesses liver X receptor (LXR) antagonistic activity, afforded novel PPAR ligands. The results of structure-activity relationship analysis and docking studies led us to the potent PPAR agonists 13c-e. The absolute configuration of 13c-e affects the PPAR subtype selectivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Drug Design
  • Humans
  • Ligands
  • Liver X Receptors
  • Models, Molecular
  • Orphan Nuclear Receptors / antagonists & inhibitors*
  • Peroxisome Proliferator-Activated Receptors / agonists*
  • Peroxisome Proliferator-Activated Receptors / chemistry
  • Peroxisome Proliferator-Activated Receptors / metabolism*
  • Phthalimides / chemistry*
  • Phthalimides / pharmacology*
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Structure-Activity Relationship
  • Thalidomide / chemistry*

Substances

  • Ligands
  • Liver X Receptors
  • Orphan Nuclear Receptors
  • Peroxisome Proliferator-Activated Receptors
  • Phthalimides
  • Receptors, Cytoplasmic and Nuclear
  • farnesoid X-activated receptor
  • Thalidomide