3,5-diamino-6-chloro-N-(2-amino-2-methylpropyl)pyrazine-2-carboxamide

• 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-N-(2-amino-2-methylpropyl)pyrazine-2-carboxamide
• 英文别名: 3,5-Diamino-N-(2-amino-2-methylpropyl)-6-chloro-2-pyrazinecarboxamide；3,5-diamino-N-(2-amino-2-methylpropyl)-6-chloropyrazine-2-carboxamide
• 化学式: C₉H₁₅ClN₆O
• 分子量: 258.711
• InChiKey: FSYJLKVJIXBSCO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 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-N-(2-amino-2-methylpropyl)pyrazine-2-carboxamide 、 苯基缩水甘油醚 在 草酸 作用下， 以 乙醇 、 异丙醇 为溶剂， 生成 3,5-diamino-6-chloro-N-[2-methyl-2-(2-hydroxy-3-phenoxypropylamino)propyl]pyrazine-2-carboxamide oxalate
  参考文献：
  名称：

  Alkanolamine derivatives

  摘要：

  化合物的公式为##STR1## 其中Ar是苯或萘基，未取代或带有一个或两个定义的取代基，或Ar是某些定义的杂环或双环芳香系统; R1是卤素，氰基，三氟甲基或三氟甲硫基; R2和R3中的任何一个是氢或烷基，或R2是氢，R3是环烷基或环烷基烷基，或R2和R3与相邻的氮原子一起形成杂环基; R4是氢和R5是氢或烷基，或R4是氢，R5和R6结合形成烷基，或R4，R5和R6结合形成烷-1-基-ω-亚基; R6和R7中的任何一个是氢或烷基，或R6连接到定义如上的R4或R4和R5上，R7是氢或烷基，或R6和R7结合形成烷基，或R6和R7中的一个是氢或烷基，另一个与下面定义的A连接; A是烷基，环烷基或环烷基烷基，或A与R6及其伴随的氮原子或R7及其伴随的氮原子一起形成吡咯烷基或哌嗪烷基; 及其酸加成盐; 制造它们的过程以及含有它们的制药组合物。这些化合物具有β-肾上腺素能阻滞和/或利尿作用。

  公开号：

  US04550111A1
• 作为产物：
  描述：

  tert-butyl (1-(3,5-diamino-6-chloropyrazine-2-carboxamido)-2-methylpropan-2-yl)carbamate 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 生成 3,5-diamino-6-chloro-N-(2-amino-2-methylpropyl)pyrazine-2-carboxamide
  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

• US4550111A
  申请人：——

  公开号：US4550111A

  公开（公告）日：1985-10-29
• 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.
• Alkanolamine derivatives
  申请人：Imperial Chemical Industries plc

  公开号：US04550111A1

  公开（公告）日：1985-10-29

  Alkanolamine derivatives of the formula ##STR1## wherein Ar is phenyl or napthyl which is unsubstituted or which bears one or two defined substituents, or Ar is certain defined heterocyclic or bicyclic aromatic systems; wherein R.sup.1 is halogen, cyano, trifluoromethyl or trifluoromethylthio; wherein either R.sup.2 and R.sup.3 each is hydrogen or alkyl, or R.sup.2 is hydrogen and R.sup.3 is cycloalkyl or cycloalkyl-alkyl, or R.sup.2 and R.sup.3 are joined to form, together with the adjacent nitrogen atom, a heterocyclic group; wherein either R.sup.4 is hydrogen and R.sup.5 is hydrogen or alkyl, or R.sup.4 is hydrogen and R.sup.5 and R.sup.6 are joined together to form alkylene, or R.sup.4, R.sup.5 and R.sup.6 are joined together to form alk-1-yl-.omega.-ylidene; wherein either R.sup.6 and R.sup.7 each is hydrogen or alkyl, or R.sup.6 is joined to R.sup.4 or to R.sup.4 and R.sup.5 as defined above and R.sup.7 is hydrogen or alkyl, or R.sup.6 and R.sup.7 are joined together to form alkylene, or one of R.sup.6 and R.sup.7 is hydrogen or alkyl and the other of R.sup.6 and R.sup.7 is joined to A as defined below; and wherein either A is alkylene, cycloalkylene or cycloalkylene-alkylene, or wherein A together with either R.sup.6 and its accompanying nitrogen atom, or R.sup.7 and its accompanying nitrogen atom, form pyrrolidine-diyl or piperidine-diyl; and acid-addition salts thereof; processes for their manufacture and pharmaceutical compositions containing them. The compounds possess .beta.-adrenergic blocking and/or diuretic activity.

  化合物的公式为##STR1## 其中Ar是苯或萘基，未取代或带有一个或两个定义的取代基，或Ar是某些定义的杂环或双环芳香系统; R1是卤素，氰基，三氟甲基或三氟甲硫基; R2和R3中的任何一个是氢或烷基，或R2是氢，R3是环烷基或环烷基烷基，或R2和R3与相邻的氮原子一起形成杂环基; R4是氢和R5是氢或烷基，或R4是氢，R5和R6结合形成烷基，或R4，R5和R6结合形成烷-1-基-ω-亚基; R6和R7中的任何一个是氢或烷基，或R6连接到定义如上的R4或R4和R5上，R7是氢或烷基，或R6和R7结合形成烷基，或R6和R7中的一个是氢或烷基，另一个与下面定义的A连接; A是烷基，环烷基或环烷基烷基，或A与R6及其伴随的氮原子或R7及其伴随的氮原子一起形成吡咯烷基或哌嗪烷基; 及其酸加成盐; 制造它们的过程以及含有它们的制药组合物。这些化合物具有β-肾上腺素能阻滞和/或利尿作用。