Discovery of novel potent GPR40 agonists containing imidazo[1,2-a]pyridine core as antidiabetic agents.
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 = 27.26 ml/h/kg, t1/2 = 5.93 h). The results indicate that I-14 could serve as a possible candidate to treat diabetes.
['Ye|Zhiwen|Z|', 'Liu|Chunxia|C|', 'Zou|Feng|F|', 'Cai|Yan|Y|', 'Chen|Bin|B|', 'Zou|Yuxing|Y|', 'Mo|Jiaxian|J|', 'Han|Ting|T|', 'Huang|Wenlong|W|', 'Qiu|Qianqian|Q|', 'Qian|Hai|H|']
D000818:Animals D001572:Benzofurans D001786:Blood Glucose D003921:Diabetes Mellitus, Experimental D003924:Diabetes Mellitus, Type 2 D004353:Drug Evaluation, Preclinical D005951:Glucose Tolerance Test D006801:Humans D007004:Hypoglycemic Agents D008297:Male D051379:Mice D008810:Mice, Inbred C57BL D010666:Phenylpropionates D011725:Pyridines D017207:Rats, Sprague-Dawley D043562:Receptors, G-Protein-Coupled D013450:Sulfones
GPR40 agonists Type 2 diabetes mellitus Hepatotoxicity Phenylpropanoic acid