Aleglitazar, a new, potent, and balanced dual PPARalpha/gamma agonist for the treatment of type II diabetes

Bioorg Med Chem Lett. 2009 May 1;19(9):2468-73. doi: 10.1016/j.bmcl.2009.03.036. Epub 2009 Mar 14.

Abstract

Design, synthesis, and SAR of novel alpha-alkoxy-beta-arylpropionic acids as potent and balanced PPARalphagamma coagonists are described. One representative thereof, Aleglitazar ((S)-2Aa), was chosen for clinical development. Its X-ray structure in complex with both receptors as well as its high efficacy in animal models of T2D and dyslipidemia are also presented.

MeSH terms

  • Animals
  • Chemistry, Pharmaceutical / methods
  • Crystallography, X-Ray / methods
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Drug Design
  • Dyslipidemias / drug therapy
  • Humans
  • Inhibitory Concentration 50
  • Ligands
  • Models, Chemical
  • Molecular Structure
  • Oxazoles / chemical synthesis*
  • Oxazoles / pharmacology*
  • PPAR alpha / agonists*
  • PPAR gamma / agonists*
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Thiophenes / chemical synthesis*
  • Thiophenes / pharmacology*

Substances

  • Ligands
  • Oxazoles
  • PPAR alpha
  • PPAR gamma
  • Receptors, Cytoplasmic and Nuclear
  • Thiophenes
  • aleglitazar