1-phenyl-3,8-diazaspiro<4,5>decanone-4 | 79139-61-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: 1-phenyl-3,8-diazaspiro<4,5>decanone-4
• 英文别名: rac-4-phenyl-2,8-diazaspiro[4.5]decan-1-one；rac-4-phenyl-2,8-diaza-spiro[4.5]decan-1-one；4-phenyl-2,8-diaza-spiro[4.5]decan-1-one；4-Phenyl-2,8-diazaspiro[4.5]decan-1-one
• CAS: 79139-61-0
• 化学式: C₁₄H₁₈N₂O
• 分子量: 230.31
• InChiKey: HQXCWUWCXHNQKU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  41.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-phenyl-3,8-diazaspiro<4,5>decanone-4 在 正丁基锂 、 pyridine-SO3 complex 、 TEA 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 二甲基亚砜 为溶剂， 生成 8-[2-(4-Fluoro-phenyl)-2-hydroxy-cyclohexyl]-4-phenyl-2,8-diaza-spiro[4.5]decan-1-one
  参考文献：
  名称：

  Discovery of 4-substituted-8-(2-hydroxy-2-phenyl-cyclohexyl)-2,8-diaza-spiro[4.5]decan-1-one as a novel class of highly selective GlyT1 inhibitors with improved metabolic stability

  摘要：

  A novel class of 4-aryl-8-(2-hydroxy-2-phenyl-cyclohexyl)-2,8-diaza-spiro[4.5]decan-1-ones have been discovered and developed as potent and selective GlyT1 inhibitors. The molecules are devoid of activity at the GlyT2 isoform and display excellent selectivities against the mu-opioid receptor as well as the Nociceptin/Orphanin FQ peptide (NOP) receptor. In particular these novel compounds 4 as well as the 4-substituted-8-(2-phenyl-cyclohexyl)-2,8-diaza-spiro[4.5]decan-1-one 3 show improved metabolic stability and pharmacokinetic profiles in rodents compared to previous triazaspiropiperidine series 1 and 2. We have also identified within these diazaspiropiperidine series a key relationship between reducing basicity of the piperidine nitrogen and reducing hERG affinity. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.05.058
• 作为产物：
  描述：

  1-phenyl-8-benzyl-3,8-diazaspiro<4,5>decane-2,4-dione 在 palladium on activated charcoal 盐酸 、 氢气 、 二异丁基氢化铝 、 溶剂黄146 作用下， 以 乙醇 、 水 、 甲苯 为溶剂， 反应 7.0h， 生成 1-phenyl-3,8-diazaspiro<4,5>decanone-4
  参考文献：
  名称：

  Parys, Marc Van; Vandewalle, Maurits, Bulletin des Societes Chimiques Belges, 1981, vol. 90, # 7, p. 757 - 766

  摘要：

  DOI：

文献信息

• Diaza-spiropiperidine derivatives
  申请人：Jolidon Synese

  公开号：US20050154000A1

  公开（公告）日：2005-07-14

  The present invention relates to compounds of formula wherein A—B, R 1 , R 2 , R 3 , R 4 , and n are as defined herein; and to pharmaceutically acceptable salts thereof. The compounds of formula I may be used in the treatment of neurological and neuropsychiatric disorders.

  本发明涉及以下式的化合物 其中 A—B，R 1 ，R 2 ， R 3 ，R 4 和n如本文所定义；以及其药学上可接受的盐。 式I的化合物可用于治疗神经系统和神经精神疾病。
• A Straightforward and Efficiently Scaleable Synthesis of Novel Racemic 4-Substituted-2,8-diazaspiro[4.5]decan-1-one Derivatives
  作者：Andrew W. Thomas、Eva A. Krafft、Anke Kurt、Axel Maier、Daniel Zimmerli

  DOI：10.1055/s-2005-918454

  日期：——

  Novel and straightforward syntheses (3-5 steps, high yields) of racemic diazaspiropiperidine derivatives based on the Michael addition of pipecolate-derived enolates to a range of nitroalkenes have been developed. The reaction has been shown to have a general scope and can be conducted on a preparatively useful scale. Isolation and identification of diazaspiropiperidine enantiomers was efficiently achieved using normal phase chiral HPLC.

  基于米氏加成反应，开发了新颖且直接的合成方法（3-5步，高产率），用于制备外消旋二氮杂螺环員啶衍生物，该方法涉及由哌可酸盐衍生的烯醇盐与一系列硝基烯烃的反应。实验证明该反应具有广泛的适用性，并可在有实际应用规模的条件下进行。通过常相手性高效液相色谱法，高效地分离和鉴定了二氮杂螺环哌啶的旋光异构体。
• Pyrazolone Compounds As Metabotropic Glutamate Receptor Agonists For The Treatment Of Neurological And Psychiatric Disorders
  申请人：Balestra Michael

  公开号：US20090069340A1

  公开（公告）日：2009-03-12

  Compounds of Formula (I), wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , X, and n are as defined for Formula (I) in the description, processes for the preparation of the compounds and new intermediates employed in the preparation, pharmaceutical compositions containing the compounds, and the use of the compounds in the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction.

  公式（I）的化合物，其中R1，R2，R3，R4，R5，R6，X和n的定义如描述中的公式（I），制备该化合物的过程以及用于制备的新中间体，含有该化合物的制药组合物以及在治疗或预防与谷氨酸功能障碍有关的神经系统和精神障碍中使用该化合物。
• WO2006/71730
  申请人：——

  公开号：——

  公开（公告）日：——
• Design and synthesis of 4-substituted-8-(2-phenyl-cyclohexyl)-2,8-diaza-spiro[4.5]decan-1-one as a novel class of GlyT1 inhibitors: Achieving selectivity against the μ opioid and nociceptin/orphanin FQ peptide (NOP) receptors
  作者：Daniela Alberati、Simona M. Ceccarelli、Synèse Jolidon、Eva A. Krafft、Anke Kurt、Axel Maier、Emmanuel Pinard、Henri Stalder、Deborah Studer、Andrew W. Thomas、Daniel Zimmerli

  DOI：10.1016/j.bmcl.2006.05.064

  日期：2006.8

  A novel class of 4-substituted-8-(2-phenyl-cyclohexyl)-2,8-diaza-spiro[4.5]decan-1-ones have been discovered and developed as potent and selective GlyT1 inhibitors. The molecules are devoid of activity at the GlyT2 isoform and display excellent selectivities against the mu opioid receptor as well as the nociceptin/orphanin FQ peptide (NOP) receptor. A novel, straightforward and efficient synthetic strategy for the assembly of the target molecules is also presented. (c) 2006 Elsevier Ltd. All rights reserved.