Discovery of azetidinone acids as conformationally-constrained dual PPARα/γ agonists

Abstract A novel class of azetidinone acid-derived dual PPARα/γ agonists has been synthesized for the treatment of diabetes and dyslipidemia. The preferred stereochemistryin this series for binding and functional agonist activity against both PPARα and PPARγ receptors was shown to be 3 S ,4 S . Synthesis, in vitro and in vivo activities of compounds in this series are described. A high-yielding method for N-arylation of azetidinone esters is also described.