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| 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 | |
| 引用本文： | 战付旭,王玉丽,赵桂龙,徐为人,李祎亮, 邹美香,汤立达,王建武 . 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[J]. 有机化学, 2009, 29(8): 1236-1242 |
| 作者姓名： | 战付旭 王玉丽 赵桂龙 徐为人 李祎亮 邹美香 汤立达 王建武 |
| 作者单位： | (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) ; |
| 摘 要： | 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 二肽基肽酶IV 合成 口服糖耐量实验 糖尿病 构效关系 |
| 收稿时间： | 2009-01-18 |
| 修稿时间： | 2009-02-26 |
Design, Synthesis and Anti-diabetic Activities of Thiazole-Bearing Compounds as Dipeptidyl Peptidase IV Inhibitors |
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| Affiliation: | (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) |
| Abstract: | 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). |
| Keywords: | thiazole dipeptidyl peptidase IV synthesis oral glucose tolerance test diabetes structure-activity relationship |
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