[5-(4-Chloro-benzenesulfonylamino)-pentyl]-{2-[(3,5-diamino-6-chloro-pyrazine-2-carbonyl)-amino]-ethyl}-dimethyl-ammonium bromide | 1201178-30-4

• 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: [5-(4-Chloro-benzenesulfonylamino)-pentyl]-{2-[(3,5-diamino-6-chloro-pyrazine-2-carbonyl)-amino]-ethyl}-dimethyl-ammonium bromide
• 英文别名: 5-[(4-chlorophenyl)sulfonylamino]pentyl-[2-[(3,5-diamino-6-chloropyrazine-2-carbonyl)amino]ethyl]-dimethylazanium;bromide
• CAS: 1201178-30-4
• 化学式: Br*C₂₀H₃₀Cl₂N₇O₃S
• 分子量: 599.379
• InChiKey: BWDRRLNAFWYFEG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.09
• 重原子数：
  34
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  162
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  3,5-二氨基-6-氯吡嗪-2-羧酸甲酯 在 N-甲基吗啉 、 一水合肼 作用下， 以 乙醇 、 二氯甲烷 、 丁酮 为溶剂， 生成 [5-(4-Chloro-benzenesulfonylamino)-pentyl]-{2-[(3,5-diamino-6-chloro-pyrazine-2-carbonyl)-amino]-ethyl}-dimethyl-ammonium bromide
  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

• Organic Comopunds
  申请人：Collingwood Stephen Paul

  公开号：US20110201625A1

  公开（公告）日：2011-08-18

  A compound of Formula I or a hydrate or solvate thereof, where R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , and R 10 have the meanings as indicated in the specification, is useful for treating diseases which respond to the blockade of the epithelial sodium channel. Pharmaceutical compositions that contain the compounds and processes for preparing the compounds are also described.

  化合物I的配方或其水合物或溶剂化物，其中R1、R2、R3、R4、R5、R6、R7、R8、R9和R10的含义如规范中所示，可用于治疗对上皮钠通道阻滞有反应的疾病。还描述了含有该化合物的制药组合物和制备该化合物的过程。
• Pyrazine derivatives as ENAC blockers
  申请人：Novartis AG

  公开号：US08236808B2

  公开（公告）日：2012-08-07

  A compound of Formula I or a hydrate or solvate thereof, where R1, R2, R3, R4, R5, R6, R7, R8, R9, and R10 have the meanings as indicated in the specification, is useful for treating diseases which respond to the blockade of the epithelial sodium channel. Pharmaceutical compositions that contain the compounds and processes for preparing the compounds are also described.

  公式I的化合物或其水合物或溶剂化物，其中R1，R2，R3，R4，R5，R6，R7，R8，R9和R10具有规范中指示的含义，可用于治疗对上皮钠通道阻滞有反应的疾病。还描述了包含这些化合物的制药组合物和制备这些化合物的过程。
• US8236808B2
  申请人：——

  公开号：US8236808B2

  公开（公告）日：2012-08-07
• 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.