含反式环己烷结构的C-葡萄糖苷类SGLT2抑制剂的设计、合成与降血糖活性研究  

Design,Synthesis and Anti-hyperglycemic Activity of trans-Cyclohexane-Bearing C-Glucosides as SGLT2 Inhibitors

作　　者：邵华[1] 高云龙[1,2] 楼袁媛[3] 王玉丽[1] 刘巍[1] 徐为人[1] 王建武[2] 赵桂龙[1] 汤立达[1] 

机构地区：[1]天津药物研究院药物设计与发现天津市重点实验室,天津300193 [2]山东大学化学与化工学院,济南250100 [3]青岛科技大学化学与分子工程学院,青岛266042

出　　处：《有机化学》2011年第6期836-842,共7页Chinese Journal of Organic Chemistry

基　　金：天津市科技支撑计划重点(No.10ZCKFSH01300);国家重大新药创新专项大平台子课题(No.2009ZX09301-008-N-11)资助项目

摘　　要：设计并合成了一系列含有反式环己烷结构的C-葡萄糖苷类SGLT2抑制剂,关键步骤是对溴苯甲醚与反式环己烷甲酰氯在无水AlCl3催化下的区域选择性Friedel-Crafts酰基化.所有化合物的结构经过了1H NMR和HRMS的表征.小鼠口服糖耐量实验(OGTT)显示,化合物11a～11d均显示较强的降血糖活性,且11c的活性超过了阳性对照药dapagliflozin,具有良好的开发前景.A series of trans-cyclohexane-bearing C-glucosides were designed and synthesized as SGLT2 inhibitors,with the key step being the region-selective Friedel-Crafts alkylation of trans-cyclohexanecar-bonyl chloride and 4-bromoanisole mediated by anhydrous aluminum chloride.All the synthesized com-pounds were characterized by 1H NMR and HRMS techniques.Evaluation of these compounds by mice oral glucose tolerance test（OGTT） revealed that all the synthesized compounds 11a-11d exhibited potent anti-hyperglycemic activity,with 11c being more potent than the positive control dapagliflozin,which is a prom-ising agent for the treatment of type 2 diabetes.

关 键 词：环己烷 C-葡萄糖苷 SGLT2抑制剂 合成 降血糖活性 糖尿病 

分 类 号：TQ463[化学工程—制药化工]