摘要
以6-氟(或7-氟)-4-氯-喹啉为原料与对二苯胺经亲核取代反应,得到4-(4'-氨基苯氨基)喹啉化合物,再与不同的酰化试剂发生酰化反应,得到12个未见文献报道的化合物,结构经过ESI-MS确认。用Molegro Virtual Docker软件完成与EGFR^(T790M)的分子对接,并用Discovery Studio 2016 Client软件分析化合物与EGFR^(T790M)的作用模式。分子对接研究表明6-氟-4-{4'-[(4″-甲氧基)-苯酰氨基]-苯氨基}-喹啉1位的氮和4″位甲氧基上的氧分别与ARG A:776和HIS A:850残基形成两个氢键。为开发EGFR^(T790M)抑制剂提供基础。
6-Fluoro( or 7-fluoro)-4-chloro-quinoline reacted with para diphenylamine to give 4-( 4'-aminophenylamino) quinoline compounds by nucleophilic substitution reaction.Acylation of 4-( 4'-aminophenyl amino) quinoline compounds with different acylation reagents yields twelve novel compounds.The structure of the target compunds was confirmed by ESI-MS.Molecular docking was performed with Molegro Virtual Docker software,The interaction between compounds and EGFRT790M was analyzed by Discovery Studio 2016 Client software.The Molecular docking showed that N of 1 position and O of 4″ position of 6-fluoro-4-{ 4'-[( 4″- methoxy)-benzoylamino]-phenylamino}-quinoline give a hydrogen bond with ARG A: 776 and HIS A: 850, respectively,which provides basis for developing EGFRT790M inhibitors.
作者
刘丹
张昕旸
袁莹
薛艾奇
LIU Dan;ZHANG Xinyang;YUAN Ying;XUE Ai-qi(College of Pharmaceutical and Biological Engineering,Shenyang University of Chemical Technology, Shenyang 110142,China)
出处
《化学试剂》
CAS
北大核心
2019年第5期441-445,共5页
Chemical Reagents
基金
辽宁省自然科学基金资助项目(201520695)
