Design,synthesis and biological activity of cyclohexane-bearing C-glucoside derivatives as SGLT2 inhibitors

作     者：Shuo Zhang Yu-Li Wang Qun-Chao Wei Wei-Ren Xu Li-Da Tang Gui-Long Zhao Jian-Wu Wang 

作者机构：School of Chemistry and Chemical EngineeringShandong University Tianjin Key Laboratory of Molecular Design and Drug DiscoveryTianjin Institute of Pharmaceutical Research 

基　　金：Key Projects of Tianjin Science and Technology Support Plan(No.10ZCKFSH01300) for financial support 

出 版 物：《Chinese Chemical Letters》 (中国化学快报（英文版）)

年 卷 期：2013年第24卷第5期

页      码：429-432页

摘      要：Seven cyclohexane-bearing C-glucoside derivatives（7,9,12,13 and 17-19） were designed and synthesized as SGLT2 inhibitors starting from a potent SGLT2 inhibitor we discovered in earlier work, （lS）-1-deoxy-l-[4-methoxy-3-（trans-n-propylcyclohexyl）methylphenyl]-D-glucose（1）.The in vitro and in vivo biological activities were evaluated by hSGLT2/hSGLTl inhibition and urinary glucose excretion （UGE）,*** the synthesized compounds 12,the 6-deoxy derivative of 1 was the most active and selective SGLT2 inhibitor（IC_（50）= 1.4nmol/L against hSGLT2;selectivity = 1576）.Compound 12 was a potent SGLT2 inhibitor,which could induce more urinary glucose than 1 and dapagliflozin in UGE.

主 题 词：Synthesis C-Glucoside SGLT2 inhibitor Urinary glucose excretion Cyclohexane-bearing 

学科分类：1007[医学-药学类] 10[医学] 

核心收录：

D　O　I：10.1016/j.cclet.2013.03.026

馆 藏 号：203980954...