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

We have developed a new class of PPARα/γ dual agonists, which show excellent agonistic activity in PPARα/γ transactivation assay. In particular, (R)-9d was identified as a potent PPARα/γ dual agonist with EC50s of 0.377 μM in PPARα and 0.136 μM in PPARγ, respectively. Interestingly, the structure–activity relationship revealed that the stereochemistry of the identified PPARα/γ dual agonists significantly affects their agonistic activities in PPARα than in PPARγ.

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