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新的PTP1B抑制剂的设计合成及构效关系研究
发表时间：2011-06-15 浏览量：1866 下载量：814
| 全部作者： | 童元峰，张裴，田金英，叶菲，吴松 |
| 作者单位： | 中国医学科学院北京协和医学院药物研究所新药研究与开发室；中国医学科学院北京协和医学院药物研究所药理室 |
| 摘 要： | 在前期以天然产物岩芹酸为先导物而发现的新型小分子蛋白酪氨酸磷酸酶-1B（protein tyrosine phosphatase 1B，PTP1B）抑制剂N-(2-十四烷氧基苯基)邻氨甲酰基苯甲酸的基础上，将该抑制剂作为先导物进行进一步的优化，设计合成一系列取代的（2-十四烷氧基苯基）氨甲酰基邻苯甲酸类衍生物，进行PTP1B活性筛选。体外活性测试结果显示：多数化合物具有抑制PTP1B的活性，部分化合物IC50值达到100 nm 左右，并对上述化合物的构效关系进行总结。 |
| 关 键 词： | 药物化学；烷氧基苯基氨甲酰基邻苯甲酸类衍生物；合成；构效关系；蛋白酪氨酸磷酸酶-1B |
| Title： | Design, synthesis and structure-activity relationship of novel PTP1B inhibitors |
| Author： | TONG Yuanfeng, ZHANG Pei, TIAN Jinying, YE Fei, WU Song |
| Organization： | Department of New Drug Research and Development, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College; Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College |
| Abstract： | Starting from the natural product petroselinic acid as lead compound, N-(2-tetradecanoxyphenylaminocarbonyl) benzoic acid was found as a small molecule protein tyrosine phosphatase 1B (PTP1B) inhibitor. For further modification, a series of (2-tetradecanoxyphenylaminocarbonyl) benzoic acid derivatives were designed and synthesized. The inhibitory activities of these compounds in vitro against PTP1B were evaluated. The results indicated that most of the derivatives showed more potent activities against PTP1B and IC50 of some compounds arrived at 100 nm in vitro. The structure-activity relationship (SAR) was summarized. |
| Key words： | medicinal chemistry; (alkoxyphenyl)-aminocarbonyl benzoic acid derivatives; synthesis; structure-activity relationship; protein tyrosine phosphates 1B |
| 发表期数： | 2011年6月第11期 |
| 引用格式： | 童元峰，张裴，田金英，等. 新的PTP1B抑制剂的设计合成及构效关系研究[J]. 中国科技论文在线精品论文，2011，4（11）：975-982. |
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