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 - 药学学报.pdf

·716 · 药学学报 Acta Pharmaceutica Sinica 2012, 47 (6): 716−724 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 1 1, 2* 万惠新 , 沈竞康 (1. 上海医药集团股份有限公司中央研究院, 上海 201203; 2. 中国科学院上海药物研究所, 新药研究国家重点实验室, 上海 201203) 摘要: 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。 关键词: 钠-葡萄糖共转运蛋白 2 抑制剂; 抗糖尿病药物; 构效关系 中图分类号: R916 文献标识码: A 文章编号: 0513-4870 (2012) 06-0716-09 Research progress of sodium-glucose co-transporter 2 inhibitors for treatment of type 2 diabetes 1 1, 2* WAN Hui-xin , SHEN Jing-kang (1. Central Research Institute, Shanghai Pharmaceutical Holding Co., Ltd., Shanghai 201203, China; 2. State Key Laboratory of Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China) Abstract : 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