| 丙二酸类PTP1B抑制剂的设计、合成及活性研究 |
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| 作者姓名： | Du X Zhang SE Liu JZ Nie FL Ye F Tian JY Xiao ZY |
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| 作者单位： | (中国医学科学院、北京协和医学院药物研究所 1. 活性物质发现与适药化研究北京市重点实验室, 2. 药理学研究室, 北京 100050) |
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| 基金项目： | 国家自然科学基金资助项目(20972192);北京市自然科学基金资助项目(7102117) |
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| 摘 要： | 蛋白酪氨酸磷酸酶 (protein tyrosine phosphatase, PTP) 1B是治疗2型糖尿病 (T2DM) 及肥胖症的潜在靶点。磷酸酪氨酸 (pTyr) 是PTP1B去磷酸化作用的底物, 本文以丙二酸基团模拟pTyr分子中的磷酸酯, 设计合成了丙二酸类PTP1B抑制剂1～7。抑酶活性评价显示, 化合物3和4对人重组PTP1B的半数抑制浓度IC50分别为7.66和1.88 μmol·L?1。
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| 关 键 词： | PTP1B抑制剂 磷酸酪氨酸模拟物 丙二酸洐生物 |
Design, synthesis and evaluation of malonic acid-based PTP1B inhibitors |
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| Du X,Zhang SE,Liu JZ,Nie FL,Ye F,Tian JY,Xiao ZY.Design, synthesis and evaluation of malonic acid-based PTP1B inhibitors[J].Acta Pharmaceutica Sinica,2012,47(3):367-373. |
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| Authors: | Du Xin Zhang Shu-En Liu Jun-Zheng Nie Fei-Lin Ye Fei Tian Jin-Ying Xiao Zhi-Yan |
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| Affiliation: | Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. |
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| Abstract: | Protein tyrosine phosphatase (PTP) 1B is a potential target for the treatment of diabetes and obesity. Phosphotyrosine (pTyr) is the substrate for PTP1B dephosphorylation. Malonic acid moiety was used herein as a mimic of the phosphate group in pTyr, and novel malonic acid derivatives 1−7 were designed, synthesized and evaluated as PTP1B inhibitors. Results from enzymatic assays indicated that compounds 3 and 4 exhibited potent inhibition against human recombinant PTP1B with IC50 values of 7.66 and 1.88 μmol·L−1, respectively. |
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| Keywords: | PTP1B inhibitors pTyr mimic malonic acid derivative |
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