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

Chin. J. Org. Chem. ›› 2011, Vol. 31 ›› Issue (06): 836-842. Previous Articles Next Articles

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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

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

(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)

收稿日期:2010-12-06 修回日期:2010-12-30 发布日期:2011-01-24
通讯作者: 赵桂龙 E-mail:zhao_guilong@126.com

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

Shao Hua¹ Gao Yunlong^1,2 Lou Yuanyuan³ Wang Yuli¹ Liu Wei¹ Xu Weiren¹ Wang Jianwu² Zhao Guilong*^,1 Tang Lida*^,1

(¹Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceu-tical Research, Tianjin 300193)
(²School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100)
(³College of Chemistry and Molecular Engineer-ing, Qingdao University of Science and Technology, Qingdao 266042)

Received:2010-12-06 Revised:2010-12-30 Published:2011-01-24

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 chlo-ride. All the synthesized compounds 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 antihyperglycemic activity, with 11c being more potent than the positive control dapagliflozin, which is a promising agent for the treatment of type 2 diabetes.

Key words: cyclohexane, C-glucoside, SGLT2 inhibitor, synthesis, anti-hyperglycemic activity, diabetes

Cite this article

SHAO Hua, GAO Yun-Long, LOU Yuan-Yuan, WANG Yu-Li, LIU Wei, XU Wei-Ren, WANG Jian-Wu, ZHAO Gui-Long, TANG Li-Da. Design, Synthesis and Anti-hyperglycemic Activity of trans- Cyclohexane-Bearing C-Glucosides as SGLT2 Inhibitors[J]. Chin. J. Org. Chem., 2011, 31(06): 836-842.

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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

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