2-((1H-indol-3-yl)methyl)-9-(pyrazin-2-yl)-2,9-diazaspiro[5.5]undecan-1-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂螺癸烷衍生物
• 英文名称: 2-((1H-indol-3-yl)methyl)-9-(pyrazin-2-yl)-2,9-diazaspiro[5.5]undecan-1-one
• 英文别名: 2-(1H-indol-3-ylmethyl)-9-pyrazin-2-yl-2,9-diazaspiro[5.5]undecan-1-one
• 化学式: C₂₂H₂₅N₅O
• 分子量: 375.473
• InChiKey: CCGWDYLPWSYNLM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  65.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-tert-butyl 4-ethyl 4-(2-cyanoethyl)piperidine-1,4-dicarboxylate 在 氨 、 氢气 、 caesium carbonate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 N,N-二异丙基乙胺 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 120.0 ℃ 、689.49 kPa 条件下， 反应 52.17h， 生成 2-((1H-indol-3-yl)methyl)-9-(pyrazin-2-yl)-2,9-diazaspiro[5.5]undecan-1-one
  参考文献：
  名称：

  Identification of a Novel Series of Orexin Receptor Antagonists with a Distinct Effect on Sleep Architecture for the Treatment of Insomnia

  摘要：

  Dual orexin receptor (OXR) antagonists (DORAs) such as almorexant, 1 (SB-649868), or suvorexant have shown promise for the treatment of insomnias and sleep disorders in several recent clinical trials in volunteers and primary insomnia patients. The relative contribution of antagonism of OX1R and OX2R for sleep induction is still a matter of debate. We therefore initiated a drug discovery project with the aim of creating both OX2R selective antagonists and DORAs. Here we report that the OX2R selective antagonist 26 induced sleep in mice primarily by increasing NREM sleep, whereas the DORA suvorexant induced sleep largely by increasing REM sleep. Thus, OX2R selective antagonists may also be beneficial for the treatment of insomnia.

  DOI：

  10.1021/jm4007627

文献信息

• Identification of a Novel Series of Orexin Receptor Antagonists with a Distinct Effect on Sleep Architecture for the Treatment of Insomnia
  作者：Claudia Betschart、Samuel Hintermann、Dirk Behnke、Simona Cotesta、Markus Fendt、Christine E. Gee、Laura H. Jacobson、Grit Laue、Silvio Ofner、Vinod Chaudhari、Sangamesh Badiger、Chetan Pandit、Juergen Wagner、Daniel Hoyer

  DOI：10.1021/jm4007627

  日期：2013.10.10

  Dual orexin receptor (OXR) antagonists (DORAs) such as almorexant, 1 (SB-649868), or suvorexant have shown promise for the treatment of insomnias and sleep disorders in several recent clinical trials in volunteers and primary insomnia patients. The relative contribution of antagonism of OX1R and OX2R for sleep induction is still a matter of debate. We therefore initiated a drug discovery project with the aim of creating both OX2R selective antagonists and DORAs. Here we report that the OX2R selective antagonist 26 induced sleep in mice primarily by increasing NREM sleep, whereas the DORA suvorexant induced sleep largely by increasing REM sleep. Thus, OX2R selective antagonists may also be beneficial for the treatment of insomnia.