(2′-溴-4,′5′-二甲氧基-苯基)-(2,3-二溴-4,5-二甲氧基-苯基)-甲烷的合成及其PTP1B酶抑制活性研究  

Synthesis of(2′-bromo-4′,5′-dimethoxy-phenyl)-(2,3-dibromo-4,5-dimethoxy-phenyl)-methane as PTP1B inhibitor

作　　者：李敬[1,2] 郭书举[1,2] 苏华[1,2] 史大永[1] 韩丽君[1] 

机构地区：[1]中国科学院海洋研究所,山东青岛266071 [2]中国科学院研究生院,北京100039

出　　处：《中国中药杂志》2009年第12期1516-1519,共4页China Journal of Chinese Materia Medica

基　　金：国家高技术研究发展计划(863)项目(2007AA09Z410,2007AA091604);中国科学院方向性创新项目(KZCX2-YW-209)

摘　　要：目的:通过化学法合成具有PTP1B酶抑制活性的新型溴酚衍生物-(2′-溴-4,′5′-二甲氧基-苯基)-(2,3-二溴-4,5-二甲氧基-苯基)-甲烷。方法:采用傅克酰基化、逐级溴化、脱羰基等经典合成反应合成目标化合物6。采用EI-MS,HREI-MS,1H-NMR,13C-NMR,IR等方法对合成中间体及目标化合物进行结构鉴定。通过比色法对化合物6进行PTP1B酶抑制活性测试。结果:采用四步法成功合成了目标化合物6,体外活性测试结果表明其具有一定的PTP1B酶抑制活性。结论:采用化学法合成了目标化合物6,总产率为20%,该化合物为新化合物,具有一定的PTP1B酶抑制活性5 mg.L-1,酶抑制率为40.16%。Objective： To synthesize （ 2＇-bromo-4＇, 5＇-dimethoxy-phenyl ） - （ 2,3- dibromo-4,5-dimethoxy-phenyl ） -methane （6） as protein tyrosine phosphatase 1B （ PTP1 B） inhibitor. Method： Compound 6 was synthesized by Friedel-Crafts reaction, bromination and decarbonylation and screened inhibitory activity against PTP1B by the colorimetric assay. The structure of synthetic intermediates and target product were identified on the basis of spectral analysis. Result： Compound 6 was synthesized successfully in four steps and evaluated for its PTP1B inhibitory activity, the screening result shown that compound 6 displayed good inhibitory activity against PTP1B. Conclusion： The target compound 6 was synthesized with the overall yield of 20%, which was a new compound and shown good inhibitory activity against PTP1B（inhibition 40. 16% at 5 mg.L^-1）.

关 键 词：(2′-溴-4 ′5′-二甲氧基-苯基)-(2 3-二溴-4 5-二甲氧基-苯基)-甲烷 PTP1B酶抑制活性 全合成 

分 类 号：R284[医药卫生—中药学]