[(2R)-1-[(3,5-diamino-6-chloropyrazine-2-carbonyl)amino]-3-methylbutan-2-yl]-trimethylazanium;iodide | 1373437-58-1

• 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: [(2R)-1-[(3,5-diamino-6-chloropyrazine-2-carbonyl)amino]-3-methylbutan-2-yl]-trimethylazanium;iodide
• CAS: 1373437-58-1
• 化学式: C₁₃H₂₄ClN₆O*I
• 分子量: 442.731
• InChiKey: NSHAALXYSRHCBT-QRPNPIFTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.24
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  107
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3,5-diamino-N-[(2R)-2-amino-3-methylbutyl]-6-chloropyrazine-2-carboxamide 、 碘甲烷 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 生成 [(2R)-1-[(3,5-diamino-6-chloropyrazine-2-carbonyl)amino]-3-methylbutan-2-yl]-trimethylazanium;iodide
  参考文献：
  名称：

  Discovery of a novel chemotype of potent human ENaC blockers using a bioisostere approach. Part 2: α-Branched quaternary amines

  摘要：

  We report the synthesis and biological evaluation of a series of novel alpha-branched pyrazinoyl quaternary amines for their ability to block ion transport via the epithelial sodium channel (ENaC) in human bronchial epithelial cells (HBECs). Compound 12g has an IC50 of 30 nM and is highly efficacious in the Guinea-pig tracheal potential difference (TPD) model of ENaC blockade with an ED50 of 1 mu g kg(-1) at 1 h. In addition the SAR results demonstrate for the first time the chiral nature of the binding site of human ENaC. As such, pyrazinoyl quaternary amines represent a promising new class of ENaC blockers for the treatment of cystic fibrosis that are structurally distinct from the pyrazinoyl guanidine chemotype found in prototypical ENaC blockers such as amiloride. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.02.067

文献信息

• Discovery of a novel chemotype of potent human ENaC blockers using a bioisostere approach. Part 2: α-Branched quaternary amines
  作者：Thomas Hunt、Hazel C. Atherton-Watson、Stephen P. Collingwood、Kevin J. Coote、Sarah Czarnecki、Henry Danahay、Catherine Howsham、Peter Hunt、Derek Paisley、Alice Young

  DOI：10.1016/j.bmcl.2012.02.067

  日期：2012.4

  We report the synthesis and biological evaluation of a series of novel alpha-branched pyrazinoyl quaternary amines for their ability to block ion transport via the epithelial sodium channel (ENaC) in human bronchial epithelial cells (HBECs). Compound 12g has an IC50 of 30 nM and is highly efficacious in the Guinea-pig tracheal potential difference (TPD) model of ENaC blockade with an ED50 of 1 mu g kg(-1) at 1 h. In addition the SAR results demonstrate for the first time the chiral nature of the binding site of human ENaC. As such, pyrazinoyl quaternary amines represent a promising new class of ENaC blockers for the treatment of cystic fibrosis that are structurally distinct from the pyrazinoyl guanidine chemotype found in prototypical ENaC blockers such as amiloride. (C) 2012 Elsevier Ltd. All rights reserved.