9-(4,6-dimethylpyrimidin-2-yl)-2-((4-phenyl-1H-pyrazol-3-yl)methyl)-2,9-diazaspiro[5.5]undecan-1-one | 1373766-11-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 9-(4,6-dimethylpyrimidin-2-yl)-2-((4-phenyl-1H-pyrazol-3-yl)methyl)-2,9-diazaspiro[5.5]undecan-1-one
• 英文别名: 9-(4,6-dimethylpyrimidin-2-yI)-2-((4-phenyl-1H-pyrazol-3-yI)methyl)-2,9-diazaspiro[5.5]undecan-1-one；9-(4,6-dimethylpyrimidin-2-yl)-2-[(4-phenyl-1H-pyrazol-5-yl)methyl]-2,9-diazaspiro[5.5]undecan-1-one
• CAS: 1373766-11-0
• 化学式: C₂₅H₃₀N₆O
• 分子量: 430.553
• InChiKey: OJNXCHMGWDYBOV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  32
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  78
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  9-(4,6-dimethylpyrimidin-2-yl)-2-((4-phenyl-1H-pyrazol-3-yl)methyl)-2,9-diazaspiro[5.5]undecan-1-one 、 碘甲烷 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 以74%的产率得到9-(4,6-dimethylpyrimidin-2-yl)-2-((1-methyl-4-phenyl-1H-pyrazol-3-yl)methyl)-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
• 作为产物：
  描述：

  2,9-diazaspiro[5.5]undecan-1-one trifluoroacetate 在 盐酸 、 4-二甲氨基吡啶 、 四丁基碘化铵 、 sodium hydride 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 2.0h， 生成 9-(4,6-dimethylpyrimidin-2-yl)-2-((4-phenyl-1H-pyrazol-3-yl)methyl)-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

• Diaza-spiro[5.5]undecanes
  申请人：BADIGER Sangamesh

  公开号：US20120101110A1

  公开（公告）日：2012-04-26

  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.

  本发明涉及具有公式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存在；其制备方法，用作药物的使用，以及包含它的药物。
• [EN] DIAZA-SPIRO[5.5]UNDECANES USEFUL AS OREXIN RECEPTOR ANTAGONISTS<br/>[FR] DIAZASPIRO[5.5]UNDÉCANES UTILES COMME ANTAGONISTES DES RÉCEPTEURS DE L'OREXINE
  申请人：NOVARTIS AG

  公开号：WO2012055888A1

  公开（公告）日：2012-05-03

  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存在；涉及其制备方法、作为药物的应用，以及包含它的药物。
• DIAZA-SPIRO[5.5]UNDECANES USEFUL AS OREXIN RECEPTOR ANTAGONISTS
  申请人：Badiger Sangamesh

  公开号：US20130281463A1

  公开（公告）日：2013-10-24

  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.

  本发明涉及公式（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，其作为药物的使用以及包含它的药物。
• 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.