3,5-Diamino-6-chloro-N-[4-(dimethylamino)butyl]-2-pyrazinecarboxamide | 1357514-60-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 3,5-Diamino-6-chloro-N-[4-(dimethylamino)butyl]-2-pyrazinecarboxamide
• 英文别名: 3,5-diamino-6-chloro-N-[4-(dimethylamino)butyl]pyrazine-2-carboxamide
• CAS: 1357514-60-3
• 化学式: C₁₁H₁₉ClN₆O
• 分子量: 286.764
• InChiKey: OPXUVRFROIYQJS-UHFFFAOYSA-N

物化性质

• 沸点：
  477.3±45.0 °C(Predicted)
• 密度：
  1.288±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  110
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-二甲基氨基丁胺 、 3,5-二氨基-6-氯吡嗪-2-羧酸 在 N-甲基吗啉 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以40%的产率得到3,5-Diamino-6-chloro-N-[4-(dimethylamino)butyl]-2-pyrazinecarboxamide
  参考文献：
  名称：

  Discovery of a novel chemotype of potent human ENaC blockers using a bioisostere approach. Part 1: Quaternary amines

  摘要：

  We report the identification of a novel series of human epithelial sodium channel (ENaC) blockers that are structurally distinct from the pyrazinoyl guanidine chemotype found in prototypical ENaC blockers such as amiloride. Following a rational design hypothesis a series of quaternary amines were prepared and evaluated for their ability to block ion transport via ENaC in human bronchial epithelial cells (HBECs). Compound 11 has an IC50 of 200 nM and is efficacious in the Guinea-pig tracheal potential difference (TPD) model of ENaC blockade with an ED50 of 44 mu g kg(-1) at 1 h. As such, pyrazinoyl quaternary amines represent the first examples of a promising new class of human ENaC blockers. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.12.016

文献信息

• Discovery of a novel chemotype of potent human ENaC blockers using a bioisostere approach. Part 1: Quaternary amines
  作者：Thomas Hunt、Hazel C. Atherton-Watson、Jake Axford、Stephen P. Collingwood、Kevin J. Coote、Brian Cox、Sarah Czarnecki、Henry Danahay、Nick Devereux、Catherine Howsham、Peter Hunt、Victoria Paddock、Derek Paisley、Alice Young

  DOI：10.1016/j.bmcl.2011.12.016

  日期：2012.1

  We report the identification of a novel series of human epithelial sodium channel (ENaC) blockers that are structurally distinct from the pyrazinoyl guanidine chemotype found in prototypical ENaC blockers such as amiloride. Following a rational design hypothesis a series of quaternary amines were prepared and evaluated for their ability to block ion transport via ENaC in human bronchial epithelial cells (HBECs). Compound 11 has an IC50 of 200 nM and is efficacious in the Guinea-pig tracheal potential difference (TPD) model of ENaC blockade with an ED50 of 44 mu g kg(-1) at 1 h. As such, pyrazinoyl quaternary amines represent the first examples of a promising new class of human ENaC blockers. (C) 2011 Elsevier Ltd. All rights reserved.