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 EGFR~(T790M) Mwas 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 EGFR~(T790M) Minhibitors.
引文
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