4-phenyl-1,9-diazaspiro[5.5]undecane | 1452809-27-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 4-phenyl-1,9-diazaspiro[5.5]undecane
• CAS: 1452809-27-6
• 化学式: C₁₅H₂₂N₂
• 分子量: 230.353
• InChiKey: KAGRHWYWHALQSN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.28
• 重原子数：
  17.0
• 可旋转键数：
  1.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  24.06
• 氢给体数：
  2.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  4-phenyl-1,9-diazaspiro[5.5]undecane 、 异氰酸间甲苯酯 以 甲苯 为溶剂， 反应 1.0h， 以64%的产率得到4-phenyl-N-(m-tolyl)-1,9-diazaspiro[5.5]undecane-9-carboxamide
  参考文献：
  名称：

  A General Approach to Spirocyclic Piperidines via Castagnoli–Cushman Chemistry

  摘要：

  源自三组分Castagnoli–Cushman反应变体的不饱和螺环内酰胺成功经过氢化反应，以便访问完全饱和的螺环内酰胺。随后的内酰胺还原产生了2-螺环哌啶构建块。后者可以在化合物库中进一步详细研究，并且本身显示出激活微量胺相关受体1（TAAR1）的倾向，这是中枢神经系统疾病的重要靶点。

  DOI：

  10.1055/s-0040-1719878
• 作为产物：
  描述：

  4-phenyl-1,9-diazaspiro[5.5]undecan-2-one 在 lithium aluminium tetrahydride 作用下， 以 乙醚 为溶剂， 反应 24.0h， 以67%的产率得到4-phenyl-1,9-diazaspiro[5.5]undecane
  参考文献：
  名称：

  A General Approach to Spirocyclic Piperidines via Castagnoli–Cushman Chemistry

  摘要：

  源自三组分Castagnoli–Cushman反应变体的不饱和螺环内酰胺成功经过氢化反应，以便访问完全饱和的螺环内酰胺。随后的内酰胺还原产生了2-螺环哌啶构建块。后者可以在化合物库中进一步详细研究，并且本身显示出激活微量胺相关受体1（TAAR1）的倾向，这是中枢神经系统疾病的重要靶点。

  DOI：

  10.1055/s-0040-1719878

文献信息

• Synthesis and evaluation of heteroaryl substituted diazaspirocycles as scaffolds to probe the ATP-binding site of protein kinases
  作者：Charlotte E. Allen、Chiau L. Chow、John J. Caldwell、Isaac M. Westwood、Rob L. M. van Montfort、Ian Collins

  DOI：10.1016/j.bmc.2013.07.021

  日期：2013.9

  With the success of protein. kinase inhibitors as drugs to target cancer, there is a continued need for new kinase inhibitor scaffolds. We have investigated the synthesis and kinase inhibition of new heteroaryl-substituted diazaspirocyclic compounds that mimic ATP. Versatile syntheses of substituted diazaspirocycles through ring-closing metathesis were demonstrated. Diazaspirocycles directly linked to heteroaromatic hinge binder groups provided ligand efficient inhibitors of multiple kinases, suitable as starting points for further optimization. The binding modes of representative diazaspirocyclic motifs were confirmed by protein crystallography. Selectivity profiles were influenced by the hinge binder group and the interactions of basic nitrogen atoms in the scaffold with acidic side-chains of residues in the ATP pocket. The introduction of more complex substitution to the diazaspirocycles increased potency and varied the selectivity profiles of these initial hits through engagement of the P-loop and changes to the spirocycle conformation, demonstrating the potential of these core scaffolds for future application to kinase inhibitor discovery. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.