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有机化学
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有机化学 ›› 2009, Vol. 29 ›› Issue (08): 1236-1242. 上一篇    下一篇

研究论文

含噻唑环的二肽基肽酶IV抑制剂的设计、合成和降血糖活性研究

战付旭a ; 王玉丽b; 赵桂龙*,b; 徐为人b; 李祎亮b;
邹美香b; 汤立达c ; 王建武*,a
  

  1. (a山东大学化学与化工学院 济南 250100)
    (b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)
    (c天津药物研究院药代动力学与药效学省部共建国家重点实验室 天津 300193)
  • 收稿日期:2009-01-18 修回日期:2009-02-26 发布日期:2009-08-30
  • 通讯作者: 赵桂龙;王建武

Design, Synthesis and Anti-diabetic Activities of Thiazole-Bearing Compounds as Dipeptidyl Peptidase IV Inhibitors

Zhan, Fuxua; Wang, Yuli b ;Zhao, Guilong*,b; Xu, Weirenb; Li, Yiliang b;Zou, Meixiangb; Tang, Lidac ; Wang, Jianwu*,a
  

  1. (a School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100) (b Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research, Tianjin 300193)
    (c Tianjintate Key Laboratory of Pharmacokinetics and Phmarcodynamics, Tianjin Institute of Pharmaceutical
    Research, Tianjin 300193)
  • Received:2009-01-18 Revised:2009-02-26 Published:2009-08-30
  • Contact: Zhao, Guilong; Wang, Jianwu

PDF

1723

被引次数

23

设计并合成了16个含噻唑环的二肽基肽酶IV (DPP-IV)抑制剂, 利用IR, 1H NMR, 13C NMR和HR-MS表征了它们的结构. 通过小鼠口服糖耐量实验测试了它们的降血糖作用, 结果显示其中两个化合物具有很强的降血糖作用, 一个与格列齐特相当, 另一个强于格列齐特, 显示了在治疗II型糖尿病方面的前景. 构效关系研究发现, 这16个化合物的构效关系呈现出明显的规律.

关键词: 唑, 糖尿病, 二肽基肽酶IV, 口服糖耐量实验, 合成, 构效关系

Sixteen thiazole-bearing compounds were designed and synthesized as dipeptidyl peptidase IV (DPP-IV) inhibitors, and characterized by IR, 1H NMR, 13C NMR and HR-MS techniques. Their activities to decrease blood glucose level were determined through a rat oral glucose tolerance test (OGTT) and the result showed that two compounds exhibited potent activities to decrease the blood glucose level, with one being compara-ble with and the other being more potent than gliclazide, which indicates that these two compounds are promising for the treatment of type II diabetes. Careful examination led to the establishment of a regular structure-activity relationship (SAR).

Key words: dipeptidyl peptidase IV, synthesis, oral glucose tolerance test, diabetes, structure-activity relationship, thiazole