dicyclopentyl (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: dicyclopentyl (4-((4-fluorobenzyl)(prop-2-yn-1-yl)amino)-1,2-phenylene)dicarbamate
• 英文别名: cyclopentyl N-[2-(cyclopentyloxycarbonylamino)-4-[(4-fluorophenyl)methyl-prop-2-ynylamino]phenyl]carbamate
• 化学式: C₂₈H₃₂FN₃O₄
• 分子量: 493.578
• InChiKey: ZQIGFDUKTPRJJZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  36
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  79.9
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 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 、 碳酸氢钠 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 生成 dicyclopentyl (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

• 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.