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

摘要: 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。

Abstract: G Protein Coupled Receptor 119 (GPR119),expressed primarily in the pancreas,liver and gastrointestinal 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 GPR119 agonists from different pharmaceutical companies and introduced our efforts in this field.