1-((adamantan-1-yl)methyl)-2-cyano-3-(pyridin-3-ylmethyl)guanidine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 1-((adamantan-1-yl)methyl)-2-cyano-3-(pyridin-3-ylmethyl)guanidine
• 英文别名: 1-(1-Adamantylmethyl)-3-cyano-2-(pyridin-3-ylmethyl)guanidine；1-(1-adamantylmethyl)-3-cyano-2-(pyridin-3-ylmethyl)guanidine
• 化学式: C₁₉H₂₅N₅
• 分子量: 323.441
• InChiKey: LHCHSXKJJHJESK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  73.1
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3-氨甲基吡啶 在 三乙胺 作用下， 以 异丙醇 为溶剂， 反应 36.0h， 生成 1-((adamantan-1-yl)methyl)-2-cyano-3-(pyridin-3-ylmethyl)guanidine
  参考文献：
  名称：

  The role of polycyclic frameworks in modulating P2X7 receptor function

  摘要：

  Herein we describe our recent attempts to target the P2X7 receptor for potential treatment of neurological disorders. This work focusses on different polycycles including carborane, adamantane or cubane, joined by either a cyanoguanidine or an amide linker to phenyl or isoquinoline moieties. We have demonstrated the superiority of the adamantyl moiety over other polycycles in terms of synthetic accessibility and biological (cellular) activity. We have also shown that an amide or cyanoguanidine linker can greatly alter the biological activity of compounds. This SAR study provides important insights into the types of functionality required to target the P2X7 receptor. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2017.10.075

文献信息

• Discovery and pharmacological evaluation of a novel series of adamantyl cyanoguanidines as P2X7 receptor antagonists
  作者：James O'Brien-Brown、Alexander Jackson、Tristan A. Reekie、Melissa L. Barron、Eryn L. Werry、Paolo Schiavini、Michelle McDonnell、Lenka Munoz、Shane Wilkinson、Benjamin Noll、Shudong Wang、Michael Kassiou

  DOI：10.1016/j.ejmech.2017.02.060

  日期：2017.4

  Here we report adamantyl cyanoguanidine compounds based on hybrids of the adamantyl amide scaffold reported by AstraZeneca and cyanoguanidine scaffold reported by Abbott Laboratories. Compound 27 displayed five-fold greater inhibitory potency than the lead compound 2 in both pore-formation and interleukin-1 beta release assays, while 35-treated mice displayed an antidepressant phenotype in behavioral studies. This SAR study provides a proof of concept for hybrid compounds, which will help in the further development of P2X(7)R antagonists. (C) 2017 Elsevier Masson SAS. All rights reserved.
• The role of polycyclic frameworks in modulating P2X7 receptor function
  作者：Timothy B. Callis、Tristan A. Reekie、James O'Brien-Brown、Erick C.N. Wong、Eryn L. Werry、Nabiha Elias、William T. Jorgensen、John Tsanaktsidis、Louis M. Rendina、Michael Kassiou

  DOI：10.1016/j.tet.2017.10.075

  日期：2018.3

  Herein we describe our recent attempts to target the P2X7 receptor for potential treatment of neurological disorders. This work focusses on different polycycles including carborane, adamantane or cubane, joined by either a cyanoguanidine or an amide linker to phenyl or isoquinoline moieties. We have demonstrated the superiority of the adamantyl moiety over other polycycles in terms of synthetic accessibility and biological (cellular) activity. We have also shown that an amide or cyanoguanidine linker can greatly alter the biological activity of compounds. This SAR study provides important insights into the types of functionality required to target the P2X7 receptor. (C) 2017 Elsevier Ltd. All rights reserved.