Thiazolidinedione (TZD) is a novel peroxides proliferator activated receptor γ (PPARγ) agonist with many side effects. Herein, we developed a series of novel TZD analogues as partial agonists targeting PPARγ. The study of anti-hyperglycemic activity and anti-inflammatory activity enabled us to identify a novel compound, 4 g, which quickly recover the blood glucose of mice at the concentration of 100 mg/kg, and show similar anti-inflammatory activity to ibuprofen at the concentration of 20 mg/kg. The competitive binding assay confirmed direct binding of 4 g to the LBD of PPARγ with IC₅₀ being 1790 nM, and dose-dependently increased the transcriptional activity of PPARγ. Besides, through computer-aided drug design software simulation docking, it was found that compound 4 g showed the best binding ability to target protein PPARγ. Furthermore, because of the introduction of benzene containing group at N3 position, the stability of H12 in the active pocket is reduced and the stability of H3 and β-fold is increased, showing the characteristics of some PPARγ agonists, based on the docking model analysis. Together, these results suggest that 4 g is a promising PPARγ agonist that deserves further investigation.

噻唑烷二酮 (TZD) 是一种新型的过氧化物增殖物激活受体γ (PPAR γ ) 激动剂，具有许多副作用。在此，我们开发了一系列新型 TZD 类似物作为靶向 PPAR γ 的部分激动剂。抗高血糖活性和抗炎活性的研究使我们能够鉴定出一种新的化合物，4 g，在 100 mg/kg 的浓度下可以迅速恢复小鼠的血糖，并在浓度为 20 mg/kg。竞争性结合试验证实4 g与 PPAR γ的 LBD直接结合，IC ₅₀为 1790 nM，并且剂量依赖性地增加了 PPAR γ的转录活性。此外，通过计算机辅助药物设计软件仿真对接，人们发现，化合物4克显示出最好的结合能力的靶蛋白PPAR γ。此外，由于在 N3 位置引入了含苯基团，H12 在活性口袋中的稳定性降低，H3 和β-折叠的稳定性增加，显示出一些 PPAR γ激动剂的特性，基于对接模型分析。总之，这些结果表明4 g是一种有前途的 PPAR γ激动剂，值得进一步研究。