Design, Synthesis and Anti-diabetic Activity of Thiadiazole-Based Thioglycosides as SGLT2 Inhibitors

Chin. J. Org. Chem. ›› 2010, Vol. 30 ›› Issue (06): 849-859. Previous Articles Next Articles

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含噻二唑环的硫代糖苷类SGLT2抑制剂的设计、合成与降血糖活性研究

王致峰¹，赵桂龙*^{,2，刘巍²，王玉丽²，邵华²，徐为人²，田来进*^,1}

¹曲阜师范大学化学与化工学院曲阜 273165)
(²天津药物研究院分子设计与药物发现天津市重点实验室天津 300193

收稿日期:2009-08-16 修回日期:2009-10-10 发布日期:2010-01-15
通讯作者: 赵桂龙 E-mail:zhao_guilong@126.com
基金资助:
科技部支撑项目(2007BAI40B01)

Design, Synthesis and Anti-diabetic Activity of Thiadiazole-Based Thioglycosides as SGLT2 Inhibitors

Wang Zhifeng¹ Zhao Guilong*^{,2 Liu Wei² Wang Yuli² Shao Hua² Xu Weiren² Tian Laijin*^,1}

¹School of Chemistry and Chemical Engineering, Qufu Normal University, Qufu 273165)
(²Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research, Tianjin 300193

Received:2009-08-16 Revised:2009-10-10 Published:2010-01-15

Abstract

22 thioglycosides with novel structure were designed and synthesized from 5-substituded phenyloxymethyl-2-mercapto-1,3,4-thiadiazole and tetra-O-acetyl-α-glycopyranosyl bromides in the presence of phase transfer catalysis (BnEt₃N^＋Br^－) at room temperature. These compounds were characterized by IR,¹H NMR, ¹³C NMR, and HR-ESI-MS techniques. Bioactivity of decreasing blood glucose was performed through in vivo by oral glucose tolerance test (OGTT) in mice. In addition, preliminary pharmacological test showed that compound 9Ah was more potent than positive control gliclazide, while compounds 9Aa and 9Bi were comparable to gliclazide in potency.

Key words: thiadiazole, thioglycoside, SGLT2 inhibitor, synthesis, anti-hyperglycemic activity

Cite this article

WANG Zhi-Feng, ZHAO Gui-Long, LIU Wei, WANG Yu-Li, SHAO Hua, XU Wei-Ren, TIAN Lai-Jin. Design, Synthesis and Anti-diabetic Activity of Thiadiazole-Based Thioglycosides as SGLT2 Inhibitors[J]. Chin. J. Org. Chem., 2010, 30(06): 849-859.

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含噻二唑环的硫代糖苷类SGLT2抑制剂的设计、合成与降血糖活性研究

Design, Synthesis and Anti-diabetic Activity of Thiadiazole-Based Thioglycosides as SGLT2 Inhibitors

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