Design, synthesis, and structure-activity relationship of carbamate-tethered aryl propanoic acids as novel PPARalpha/gamma dual agonists

Bioorg Med Chem Lett. 2007 Jul 1;17(13):3595-8. doi: 10.1016/j.bmcl.2007.04.057. Epub 2007 Apr 25.

Abstract

We have developed a new class of PPARalpha/gamma dual agonists, which show excellent agonistic activity in PPARalpha/gamma transactivation assay. In particular, (R)-9d was identified as a potent PPARalpha/gamma dual agonist with EC(50)s of 0.377 microM in PPARalpha and 0.136 microM in PPARgamma, respectively. Interestingly, the structure-activity relationship revealed that the stereochemistry of the identified PPARalpha/gamma dual agonists significantly affects their agonistic activities in PPARalpha than in PPARgamma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbamates / chemical synthesis*
  • Carbamates / chemistry*
  • Chemistry, Pharmaceutical / methods*
  • Drug Design
  • Glycine / analogs & derivatives
  • Glycine / chemistry
  • Models, Chemical
  • Models, Molecular
  • Molecular Structure
  • Oxazoles / chemistry
  • PPAR alpha / agonists*
  • PPAR alpha / metabolism
  • PPAR gamma / agonists*
  • PPAR gamma / metabolism
  • Propionates / chemistry*
  • Rosiglitazone
  • Stereoisomerism
  • Structure-Activity Relationship
  • Thiazolidinediones / pharmacology
  • Transcriptional Activation

Substances

  • Carbamates
  • Oxazoles
  • PPAR alpha
  • PPAR gamma
  • Propionates
  • Thiazolidinediones
  • Rosiglitazone
  • propionic acid
  • Glycine
  • muraglitazar