Abstract: Recent studies indicate that insulin-sensitizing activity of TZDs occurs through the inhibition of PPARγ Ser273 phosphorylation mediated by cyclin-dependent kinase 5(Cdk5), which is resulted from the binding activity for PPARγ. While, the side effects of TZDs may be related to the agonistic potency for PPARγ. In this article, 15 target compounds were designed and synthesized based on the structure of PPAR γ partial agonist INT131, with the aim of maintaining the insulin-sensitizing activity and reducing the side effects of INT131. The structures of these compounds were confirmed by ¹H NMR and ESI-MS, and their binding activities and agonistic potencies for PPARγ were measured. The binding activity of compound 15 is 88.47% of rosiglitazone, which is similar to INT131 (98.55%), but the agonistic potency of compound 15 is 1.41% of rosiglitazone, obviously lower than INT131 (15.18%).