3-乙基-6-甲氧基苯并[d]异噁唑-5-胺的合成及类药性评价  

The Synthesis and Drug-like Evaluation of 3-Ethyl-6-methoxybenzo[d]isoxazole-5-amine

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作  者:张茂风 张悦 程新宇 刘竺云[1,2] ZHANG Mao-feng;ZHANG Yue;CHENG Xin-yu;LIU Zhu-yun(College of Pharmacy,Taizhou Polytechnic College,Taizhou 225300,China;Jiangsu Solid Preparation Engineering Technology Research and Development Center,Taizhou 225300,China)

机构地区:[1]泰州职业技术学院药学院,江苏泰州225300 [2]江苏省固体制剂工程技术研究开发中心,江苏泰州225300

出  处:《精细化工中间体》2020年第5期16-20,共5页Fine Chemical Intermediates

基  金:江苏省高校自然科学研究资助项目(19KJB350011);江苏省大学生创新创业训练计划资助项目(202012106018Y)。

摘  要:以2,4-二甲氧基苯胺为原料,经酰胺化、傅克酰基化、肟化、环合及水解5步反应,合成了新骨架3-乙基-6-甲氧基苯并[d]异噁唑-5-胺(1)。对关键步骤的反应机理进行分析,筛选合成方法,优化后处理操作工艺。该方法原料易得,操作简单,且收率较高。目标化合物经1H NMR、13C NMR、 MS和IR确证。此外,分子对接及类药性计算表明,化合物1可有效结合到BRD4溴结构域口袋,也具有良好的类药性。The novel scaffold of 3-ethyl-6-methoxybenzo[d]isoxazole-5-amine(1) was synthesized in five steps including amidation, Friedel-Crafts acylation, oximation, cyclization and hydrolyzation using 2,4-dimethoxyaniline as the starting material. The reaction mechanism of the key step was analyzed, the synthetic method was screened and the post-processing operation was optimized. The method had the advantages of easy availability of raw materials,simple operation and high yield. The target compound was confirmed by1 H NMR,13 C NMR, MS and IR. In addition,molecular docking and drug-like calculations showed that compound 1 could effectively bind to the BRD4 bromodomain pocket and possessed good drug-like properties.

关 键 词:3-乙基-6-甲氧基苯并[d]异噁唑-5-胺 傅克反应 类药性 BRD4抑制剂 

分 类 号:O626.2[理学—有机化学]

 

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