Free fatty acid receptor 1 (FFA1 or GPR40) has been studied for many years as a target for the treatment of type 2 diabetes mellitus. In order to increase potency and reduce hepatotoxicity, a series of novel compounds containing imidazo[1,2-a]pyridine scaffold as GPR40 agonist were synthesized. Compound I-14 was identified as an effective agonist as shown by the conspicuous drop in blood glucose in normal and diabetic mice. It had no risk of hepatotoxicity compared with TAK-875. Moreover, good pharmacokinetic (PK) properties of I-14 were observed (CL=27.26mL/h/kg, t_1/2=5.93h). The results indicate that I-14 could serve as a possible candidate to treat diabetes.

游离脂肪酸受体1（FFA1或GPR40）已作为治疗2型糖尿病的靶标进行了多年研究。为了增加效力并降低肝毒性，合成了一系列含有咪唑并[1,2-a]吡啶骨架作为GPR40激动剂的新型化合物。如正常和糖尿病小鼠中血糖的显着下降所示，化合物I-14被鉴定为有效的激动剂。与TAK-875相比，它没有肝毒性的风险。此外，观察到I-14具有良好的药代动力学（PK）性质（CL ＝ 27.26mL / h / kg，t _1/2＝ 5.93h）。结果表明I-14可以作为治疗糖尿病的可能候选者。