G蛋白偶联受体119激动剂及其构效关系的研究进展

Advances of G protein coupled receptor 119 agonists and their structure-activity relationship

G蛋白偶联受体119是治疗2型糖尿病的新靶点,它主要在胰腺、肝脏和胃肠道中表达。GPR119激动剂使细胞内环磷酸腺苷(cAMP)水平上升,导致胰岛素分泌增加,胰高血糖素样肽-1(GLP-1)和抑胃肽(GIP)的释放增加,从而达到治疗2型糖尿病的目的。本文通过分析各个企业的GPR119激动剂的研发情况,综述了其构效关系,并介绍本课题组在GPR119激动剂设计和合成方面的研究进展。

G Protein Coupled Receptor 119 （GPR119）, expressed primarily in the pancreas, liver and gastroin- testinal tract, is a new target for the treatment of type 2 diabetes mellitus （ T2DM）. GPR119 agonists can rise the level of intracellular cAMP, leading to increased glucose-dependent insulin, GLP-1 （glucagon-like peptide 1） and GIP （ gastric inhibitory peptide） secretion. Therefore, they play an important role in the treatment of T2DM. This review summarizes the research progress on the structure-activity relationships of GPRll9 agonists from different pharmaceutical companies and introduced our efforts in this field.