9-(quinoxalin-2-yl)-1-((1-tosyl-1H-indol-4-yl)methyl)-1,9-diazaspiro[5.5]undecan-2-one | 1313236-82-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 9-(quinoxalin-2-yl)-1-((1-tosyl-1H-indol-4-yl)methyl)-1,9-diazaspiro[5.5]undecan-2-one
• 英文别名: 1-[[1-(4-methylphenyl)sulfonylindol-4-yl]methyl]-9-quinoxalin-2-yl-1,9-diazaspiro[5.5]undecan-2-one
• CAS: 1313236-82-6
• 化学式: C₃₃H₃₃N₅O₃S
• 分子量: 579.723
• InChiKey: WKMHNNSWOLLUQE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  42
• 可旋转键数：
  5
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  96.8
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  9-(quinoxalin-2-yl)-1-((1-tosyl-1H-indol-4-yl)methyl)-1,9-diazaspiro[5.5]undecan-2-one 在 caesium carbonate 作用下， 以 甲醇 为溶剂， 生成 1-((1H-indol-4-yl)methyl)-9-(quinoxalin-2-yl)-1,9-diazaspiro[5.5]undecan-2-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
• 作为产物：
  描述：

  1-[(4-methylphenyl)sulfonyl]-1H-indole-4-carbonitrile 在 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 、 palladium 10% on activated carbon 氨 、 氢气 、 potassium carbonate 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 80.0 ℃ 、101.33 kPa 条件下， 反应 54.5h， 生成 9-(quinoxalin-2-yl)-1-((1-tosyl-1H-indol-4-yl)methyl)-1,9-diazaspiro[5.5]undecan-2-one
  参考文献：
  名称：

  [EN] DIAZA-SPIRO[5.5]UNDECANES AS OREXIN RECEPTOR ANTAGONISTS
  [FR] DIAZA-SPIRO[5.5]UNDÉCANES EN TANT QU'ANTAGONISTES DE RÉCEPTEURS D'OREXINE

  摘要：

  本发明涉及公式(I)的化合物，其中取代基如说明书中所定义；以自由形式或盐形式；其制备方法，用作药物及其药物组合物。

  公开号：

  WO2011076747A1

文献信息

• DIAZA-SPIRO[5.5]UNDECANES
  申请人：Badiger Sangamesh

  公开号：US20120264748A1

  公开（公告）日：2012-10-18

  The invention relates to compound of the formula (I), in which the substituents are as defined in the specification; in free form or in salt form; to its preparation, to its use as medicament and to medicaments comprising it.

  本发明涉及式(I)的化合物，其中取代基如规范中所定义；以自由形式或盐形式存在；其制备方法，其用作药物及包含其的药物。
• Diaza-spiro[5.5]undecanes
  申请人：Badiger Sangamesh

  公开号：US08530648B2

  公开（公告）日：2013-09-10

  The invention relates to compound of the formula (I), in which the substituents are as defined in the specification; in free form or in salt form; to its preparation, to its use as medicament and to medicaments comprising it.

  该发明涉及公式（I）的化合物，其中取代基如规范中定义；以自由形式或盐形式存在；其制备方法，作为药物的使用以及包含它的药物。
• DIAZA-SPIRO[5.5]UNDECANES AS OREXIN RECEPTOR ANTAGONISTS
  申请人：Novartis AG

  公开号：EP2516439B1

  公开（公告）日：2014-01-22
• US8530648B2
  申请人：——

  公开号：US8530648B2

  公开（公告）日：2013-09-10
• 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.