3,5-diamino-6-chloro-pyrazine-2-carboxylic acid ((S)-2-aminopentyl)-amide | 1196038-13-7

• 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-pyrazine-2-carboxylic acid ((S)-2-aminopentyl)-amide
• 英文别名: 3,5-diamino-N-[(2S)-2-aminopentyl]-6-chloropyrazine-2-carboxamide
• CAS: 1196038-13-7
• 化学式: C₁₀H₁₇ClN₆O
• 分子量: 272.738
• InChiKey: QQEMSRYJAFDYDR-YFKPBYRVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  133
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3,5-diamino-6-chloro-pyrazine-2-carboxylic acid ((S)-2-aminopentyl)-amide 、 3-(4-甲氧基苯基)丙醛 在 三乙酰氧基硼氢化钠 作用下， 以 二氯甲烷 为溶剂， 以69%的产率得到3,5-diamino-6-chloro-pyrazine-2-carboxylic acid {(S)-2-[3-(4-methoxy-phenyl)-propylamino]-pentyl}-amide
  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
• 作为产物：
  描述：

  (S)-(+)-2-氨基-1-戊醇 在 N-甲基吗啉 、 盐酸 、 一水合肼 、 三乙胺 、 三苯基膦 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 偶氮二甲酸二乙酯 作用下， 以 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 3,5-diamino-6-chloro-pyrazine-2-carboxylic acid ((S)-2-aminopentyl)-amide
  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

• [EN] 3,5-DIAMINO-6-CHLORO-PYRAZINE-2-CARBOXYLIC ACID DERIVATIVES AND THEIR USE AS EPITHELIAL SODIUM CHANNEL BLOCKERS FOR THE TREATMENT OF ARWAY DISEASES<br/>[FR] DÉRIVÉS D'ACIDE 3,5-DIAMINO-6-CHLOROPYRAZINE-2-CARBOXYLIQUE ET LEUR UTILISATION COMME BLOQUEUR DU CANAL SODIQUE ÉPITHÉLIAL POUR LE TRAITEMENT DE MALADIES DES VOIES AÉRIENNES
  申请人：NOVARTIS AG

  公开号：WO2009138378A1

  公开（公告）日：2009-11-19

  A compound of Formula (I) in free or salt or solvate form, where R1, R2, R3, R4, R5, R6, R7, R8 and R9 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）的化合物以自由或盐或溶剂形式存在，其中R1、R2、R3、R4、R5、R6、R7、R8和R9的含义如规范中所示，对于治疗对上皮钠通道阻滞有响应的疾病是有用的。还描述了含有这些化合物的药物组合物以及制备这些化合物的方法。
• 3,5-DIAMINO-6-CHLORO-PYRAZINE-2-CARBOXYLIC ACID DERIVATIVES AND THEIR USE AS EPITHELIAL SODIUM CHANNEL BLOCKERS FOR THE TREATMENT OF AIRWAY DISEASES
  申请人：Collingwood Stephen Paul

  公开号：US20110059989A1

  公开（公告）日：2011-03-10

  A compound of Formula I in free or salt or solvate form, where R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and R 9 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的化合物以自由或盐或溶剂的形式存在，其中R1、R2、R3、R4、R5、R6、R7、R8和R9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。还描述了包含该化合物的制药组合物和制备该化合物的过程。
• 3,5-DIAMINO-6-CHLORO-PYRAZINE-2-CARBOXYLIC ACID DERIVATIVES AND THEIR USE AS EPITHELIAL SODIUM CHANNEL BLOCKERS FOR THE TREATMENT OF ARWAY DISEASES
  申请人：Novartis AG

  公开号：EP2285785A1

  公开（公告）日：2011-02-23
• US8664228B2
  申请人：——

  公开号：US8664228B2

  公开（公告）日：2014-03-04