Design, synthesis, and structure–activity relationship of carbamate-tethered aryl propanoic acids as novel PPARα/γ dual agonists

Bioorganic & Medicinal Chemistry Letters
2007.0

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.

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