Synthesis and biological activity of novel α-substituted β-phenylpropionic acids having pyridin-2-ylphenyl moiety as antihyperglycemic agents

Graphic We previously reported the identification of novel oximes having 5-benzyl-2,4-thiazolidinedione with antihyperglycemic activity. We now report the synthesis and biological activity of a novel series of oximes and amides having α-substituted-β-phenylpropionic acids. In this series, we obtained potent PPARα/γ dual agonist ( S)- 9d, with which activation of PPARα and PPARγ was considerably more potent than that of the reference compounds GW9578 22 and rosiglitazone 3, respectively. This means ( S)- 9d is of the strongest class of PPARα/γ dual agonists. In the course of this study, we also obtained 8h, which indicated potent plasma glucose lowering effect in spite of weak PPARα/γ agonistic activity.