Design and synthesis of a potent and selective triazolone-based peroxisome proliferator-activated receptor alpha agonist

J Med Chem. 2003 Nov 20;46(24):5121-4. doi: 10.1021/jm034173l.

Abstract

A new series of hPPARalpha agonists containing a 2,4-dihydro-3H-1,2,4-triazol-3-one (triazolone) core is described leading to the discovery of 5 (LY518674), a highly potent and selective PPARalpha agonist.

MeSH terms

  • Administration, Oral
  • Animals
  • Apolipoprotein A-I / genetics
  • Binding, Competitive
  • Biological Availability
  • Cell Line
  • Dogs
  • Drug Design
  • Humans
  • Mice
  • Mice, Transgenic
  • Propionates / chemical synthesis*
  • Propionates / chemistry
  • Propionates / pharmacology
  • Radioligand Assay
  • Rats
  • Receptors, Cytoplasmic and Nuclear / agonists*
  • Structure-Activity Relationship
  • Transcription Factors / agonists*
  • Transcription Factors / metabolism
  • Transfection
  • Triazoles / chemical synthesis*
  • Triazoles / chemistry
  • Triazoles / pharmacology

Substances

  • Apolipoprotein A-I
  • LY 518674
  • Propionates
  • Receptors, Cytoplasmic and Nuclear
  • Transcription Factors
  • Triazoles