diethyl (4-((4-fluorobenzyl)(prop-2-yn-1-yl)amino)-1,2-phenylene)dicarbamate

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: diethyl (4-((4-fluorobenzyl)(prop-2-yn-1-yl)amino)-1,2-phenylene)dicarbamate
• 英文别名: ethyl N-[2-(ethoxycarbonylamino)-4-[(4-fluorophenyl)methyl-prop-2-ynylamino]phenyl]carbamate
• 化学式: C₂₂H₂₄FN₃O₄
• 分子量: 413.449
• InChiKey: IXCVFHVYOARRRS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  30
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  79.9
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  diethyl (4-((4-fluorobenzyl)(prop-2-yn-1-yl)amino)-1,2-phenylene)dicarbamate 、 烯丙醇 在 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 作用下， 以 二氯甲烷 为溶剂， 以85%的产率得到ethyl 2-(ethoxy carbonylimino)-4-[N-para-fluorobenzyl-N-1-(6-hydroxyl-2-alkenyl-3-hexylene)imino]aniline formate
  参考文献：
  名称：

  NOVEL COMPOUND AS KCNQ POTASSIUM CHANNEL AGONIST, PREPARATION METHOD THEREFOR AND USE THEREOF

  摘要：

  本发明提供了具有一般式I表示的结构的化合物，其药学上可接受的盐，制备方法以及在制备治疗神经系统疾病药物中的用途。该化合物或其药物组成物可用作治疗神经系统疾病的KCNQ钾通道激动剂。与现有技术中的一种化合物雷替加宾相比，本发明的化合物具有相同或更好的治疗效果，更容易合成和储存，且不易氧化恶化。

  公开号：

  US20140336252A1
• 作为产物：
  描述：

  2-氨基-5-[(4-氟苄基)氨基]-1-硝基苯 在 palladium on activated charcoal 、 氢气 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 diethyl (4-((4-fluorobenzyl)(prop-2-yn-1-yl)amino)-1,2-phenylene)dicarbamate
  参考文献：
  名称：

  Discovery of Novel Retigabine Derivatives as Potent KCNQ4 and KCNQ5 Channel Agonists with Improved Specificity

  摘要：

  Recent research suggests that KCNQ isoforms, particularly the KCNQ4 and KCNQS subtypes expressed in smooth muscle cells, are involved in both establishing and maintaining resting membrane potentials and regulating smooth muscle contractility. Retigabine (RTG) is a first-in-class antiepileptic drug that potentiates neuronal KCNQpotassium channels, but poor subtype selectivity limits its further application as a pharmacological tool. In this study, we improved the subtype specificity of retigabine by altering the N-1/3 substituents and discovered several compounds that show better selectivity for KCNQ4 and KCNQS channels. Among these compounds, 10g is highly selective for KCNQ4 and KCNQS channels without potentiating KCNQ1 and KCNQ2 channels. These results are an advance in the exploration of small molecule modifiers that selectively activate different KCNQ isoforms. The developed compounds could also serve as new pharmacological tools for elucidating the function of KCNQ channels natively expressed in various tissues.

  DOI：

  10.1021/acsmedchemlett.8b00315

文献信息

• US9353048B2
  申请人：——

  公开号：US9353048B2

  公开（公告）日：2016-05-31
• NOVEL COMPOUND AS KCNQ POTASSIUM CHANNEL AGONIST, PREPARATION METHOD THEREFOR AND USE THEREOF
  申请人：SHANGHAI INSTITUTE OF MATERIA MEDICA, CHINESE ACADEMY OF SCIENCES

  公开号：US20140336252A1

  公开（公告）日：2014-11-13

  The present invention provides compounds having the structure represented by general formula I, pharmaceutically acceptable salts thereofagonist, preparation methods therefor and a use thereof in the preparation of a medicine for the treatment of nervous system diseases. The compounds or pharmaceutical compositions thereof can be used as the KCNQ potassium channel agonist for treating nervous system diseases. Compared to retigabine, a compound in the prior art, the compound of the present invention have the same or better therapeutic effect, are easier for synthesis and storage, and less prone to oxidate deterioration.

  本发明提供了具有一般式I表示的结构的化合物，其药学上可接受的盐，制备方法以及在制备治疗神经系统疾病药物中的用途。该化合物或其药物组成物可用作治疗神经系统疾病的KCNQ钾通道激动剂。与现有技术中的一种化合物雷替加宾相比，本发明的化合物具有相同或更好的治疗效果，更容易合成和储存，且不易氧化恶化。
• Discovery of Novel Retigabine Derivatives as Potent KCNQ4 and KCNQ5 Channel Agonists with Improved Specificity
  作者：Lei Wang、Guan-Hua Qiao、Hai-Ning Hu、Zhao-Bing Gao、Fa-Jun Nan

  DOI：10.1021/acsmedchemlett.8b00315

  日期：2019.1.10

  Recent research suggests that KCNQ isoforms, particularly the KCNQ4 and KCNQS subtypes expressed in smooth muscle cells, are involved in both establishing and maintaining resting membrane potentials and regulating smooth muscle contractility. Retigabine (RTG) is a first-in-class antiepileptic drug that potentiates neuronal KCNQpotassium channels, but poor subtype selectivity limits its further application as a pharmacological tool. In this study, we improved the subtype specificity of retigabine by altering the N-1/3 substituents and discovered several compounds that show better selectivity for KCNQ4 and KCNQS channels. Among these compounds, 10g is highly selective for KCNQ4 and KCNQS channels without potentiating KCNQ1 and KCNQ2 channels. These results are an advance in the exploration of small molecule modifiers that selectively activate different KCNQ isoforms. The developed compounds could also serve as new pharmacological tools for elucidating the function of KCNQ channels natively expressed in various tissues.