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有机化学
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有机化学 ›› 2010, Vol. 30 ›› Issue (06): 849-859. 上一篇    下一篇

研究论文

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. 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   

  1. 1 School of Chemistry and Chemical Engineering, Qufu Normal University, Qufu 273165)
    (2 Tianjin 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

PDF

1480

被引次数

35 | 7

在相转移催化剂BnEt3N＋Br－作用下, 利用5-取代苯氧甲基-2-巯基-1,3,4-噻二唑与α-溴代四乙酰基吡喃糖室温反应, 合成了22个结构新颖的硫代糖苷类SGLT2抑制剂化合物, 结构经IR , 1H NMR, 13C NMR和HR-ESI-MS谱表征确认. 采用小鼠口服葡萄糖耐受量法测定了目标化合物在治疗糖尿病方面的活性, 结果发现化合物9Ah有明显的降糖作用, 而9Aa和9Bi与对照药物格列齐特相当.

关键词: 噻二唑, 硫代糖苷, SGLT2抑制剂, 合成, 降糖活性

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