[(2S)-1-[(3,5-diamino-6-chloropyrazine-2-carbonyl)amino]propan-2-yl]-trimethylazanium;iodide | 1201176-61-5

• 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: [(2S)-1-[(3,5-diamino-6-chloropyrazine-2-carbonyl)amino]propan-2-yl]-trimethylazanium;iodide
• CAS: 1201176-61-5
• 化学式: C₁₁H₂₀ClN₆O*I
• 分子量: 414.677
• InChiKey: HUVCOWVEFWUSRC-RGMNGODLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.88
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.55
• 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-[(2S)-2-aminopropyl]-6-chloropyrazine-2-carboxamide 、 碘甲烷 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 生成 [(2S)-1-[(3,5-diamino-6-chloropyrazine-2-carbonyl)amino]propan-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

• 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 EPITHELIAL SODIUM CHANNEL BLOCKERS
  申请人：Novartis AG

  公开号：EP2300010B1

  公开（公告）日：2015-03-04
• ORGANIC COMPOUNDS
  申请人：Novartis AG

  公开号：EP2300010A2

  公开（公告）日：2011-03-30
• US8236808B2
  申请人：——

  公开号：US8236808B2

  公开（公告）日：2012-08-07
• [EN] ORGANIC COMPOUNDS<br/>[FR] COMPOSÉS ORGANIQUES
  申请人：NOVARTIS AG

  公开号：WO2009150137A2

  公开（公告）日：2009-12-17

  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.