N-(2-Dimethylaminoethyl)-3,5-diamino-6-chloropyrazine-2-carboxamide | 146940-46-7

• 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: N-(2-Dimethylaminoethyl)-3,5-diamino-6-chloropyrazine-2-carboxamide
• 英文别名: 3,5-Diamino-6-chloro-N-[2-(dimethylamino)ethyl]-2-pyrazinecarboxamide；3,5-diamino-6-chloro-N-[2-(dimethylamino)ethyl]pyrazine-2-carboxamide
• CAS: 146940-46-7
• 化学式: C₉H₁₅ClN₆O
• 分子量: 258.711
• InChiKey: PNBRFHAEUNXRBD-UHFFFAOYSA-N

物化性质

• 沸点：
  450.5±45.0 °C(Predicted)
• 密度：
  1.365±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  110
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-(2-Dimethylaminoethyl)-3,5-diamino-6-chloropyrazine-2-carboxamide 在 一水合肼 作用下， 以 乙醇 、 丁酮 为溶剂， 生成 (4-Amino-butyl)-{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
• 作为产物：
  描述：

  3,5-二氨基-6-氯吡嗪-2-羧酸甲酯 、 N,N-二甲基乙二胺 反应 22.0h， 以51%的产率得到N-(2-Dimethylaminoethyl)-3,5-diamino-6-chloropyrazine-2-carboxamide
  参考文献：
  名称：

  新型阿米洛利类似物的制备及利尿特性

  摘要：

  合成了 15 种新型阿米洛利类似物，并将它们的利尿特性与白色 wistar 大鼠中的阿米洛利和氨苯蝶啶进行了比较。虽然 6 位取代的衍生物都没有表现出显着的利钠和抗利尿作用，但发现在 2 位修饰的化合物中有 5 种与标准品相同或更好。就化学结构和物理化学性质对结果进行了讨论。

  DOI：

  10.1002/ardp.19923251204

文献信息

• Preparation and Diuretic Properties of Novel Amiloride Analogues
  作者：Thomas Russ、Walter Ried、Frank Ullrich、Ernst Mutschler

  DOI：10.1002/ardp.19923251204

  日期：——

  Fifteen novel amiloride analogues were synthesized and their diuretic properties compared to amiloride and triamterene in white wistar rats. Whereas none of the 6‐substituted derivatives exhibited significant natriuretic and antikaliuretic effects, five of the compounds modified in the 2‐position were found equal or better than standards. The results are discussed with respect to chemical structure

  合成了 15 种新型阿米洛利类似物，并将它们的利尿特性与白色 wistar 大鼠中的阿米洛利和氨苯蝶啶进行了比较。虽然 6 位取代的衍生物都没有表现出显着的利钠和抗利尿作用，但发现在 2 位修饰的化合物中有 5 种与标准品相同或更好。就化学结构和物理化学性质对结果进行了讨论。
• 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。
• ORGANIC COMPOUNDS
  申请人：Novartis AG

  公开号：EP2300010A2

  公开（公告）日：2011-03-30
• [EN] ENaC BLOCKERS<br/>[FR] BLOQUEURS DU CANAL ENAC
  申请人：GLAXO GROUP LTD

  公开号：WO2011028740A1

  公开（公告）日：2011-03-10

  The present invention relates to quaternary amide analogs, pharmaceutical compositions containing them and their use as ENaC blockers.