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新型嘧啶类EGFR^(T790M)抑制剂的合成、体外抗肿瘤活性及分子对接研究

The synthesis and antitumor activities and molecular docking of novel pyrimidine EGFR^(T790M) inhibitors
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摘要 目的设计合成新型嘧啶类EGFRT790M抑制剂,并评价其抗肿瘤活性,初步探讨活性化合物与靶蛋白的结合模式。方法以2,4,5-三氯嘧啶为原料,经亲核取代反应、还原反应和偶联反应,运用分步合成法完成嘧啶类新化合物的合成,采用ELISA法测定目标化合物体外抗肿瘤活性,利用Autodock软件完成计算机辅助分子对接研究。结果与结论合成了10个未见文献报道的新化合物;体外抗肿瘤活性评价结果表明,化合物8a和8f对EGFRT790M激酶具有强烈的抑制活性;分子对接实验表明化合物8f的喹唑啉基团与Gln-791残基形成了氢键作用力。 A series of novel EGFR^T790M inhibitors containing pyrirnidine moiety as the pharmacophore were synthesized and their antitumor activities were evaluated. The target compounds were synthesized via step method. The antitumor activities of 10 new compounds were evaluated against EGF^T790 M kinases by an enzyme-linked immunosorbent assay （ELISA）. Preliminary results showed that some inhibitors, such as 8a and 8f, displayed significant antitumor activity. The molecular docking revealed that quinazoline group of compound 8f give a hydrogen bond with Gln-791 in EGFR^T790M.
作者 张颖 陈凌峰 张乔乔 韩田振 何帆 王文怡 潘恺凌 刘志国 梁广
机构地区 温州医科大学药学院
出处 《中国药物化学杂志》 CAS CSCD 2015年第4期269-274,共6页 Chinese Journal of Medicinal Chemistry
基金 国家自然科学基金项目(21472142) 浙江省大学生科技创新活动计划项目(2014R413005) 温州医科大学本专科学生科研项目(wyx201401062)
关键词 表皮生长因子受体 嘧啶 抗肿瘤活性 epidermal growth factor receptor pyrimidine antitumor activity
分类号 R914 [医药卫生—药物化学]
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参考文献11

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中国药物化学杂志
2015年 第4期

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