2型糖尿病治疗靶点钠-葡萄糖共转运蛋白2抑制剂研究进展

Research progress of sodium-glucose co-transporter 2 inhibitors for treatment of type 2 diabetes

钠-葡萄糖共转运蛋白2(sodium-glucose co-transporter 2,SGLT-2)分布在肾脏近曲小管S1部位,负责肾脏中约90%葡萄糖的重吸收,抑制SGLT-2可以促进糖尿病患者尿糖的排出,因此SGLT-2抑制剂被认为是一种新型的具有独特作用机制的抗糖尿病药物。本文按照化合物的结构特征分类,重点介绍O-芳基糖苷类、C-芳基糖苷类、O,C-螺环芳基糖苷类、N-芳基糖苷类以及非糖苷类SGLT-2抑制剂的构效关系以及最新研究进展。

Sodium-glucose co-transporters are a family of glucose transporter found in the intestinal mucosa of the small intestine（SGLT-2） and the proximal tubule of the nephron（SGLT-1 and SGLT-2）.They contribute to renal glucose reabsorption and most of renal glucose（about 90%） is reabsorbed by SGLT-2 located in the proximal renal tubule.Selectively inhibiting activity of SGLT-2 is an innovative therapeutic strategy for treatment of type 2 diabetes by enhancing urinary glucose excretion from the body.Therefore SGLT-2 inhibitors are considered to be potential antidiabetic drugs with an unique mechanism.This review will highlight some recent advances and structure-activity relationships in the discovery and development of SGLT-2 inhibitors including O-glycoside,C-glycoside,C,O-spiro glycoside and non glycosides.