1,3,9-tribenzyl-1,9-diazaspiro[5.5]undecan-2-one hydrochloride | 1452809-30-1

• 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: 1,3,9-tribenzyl-1,9-diazaspiro[5.5]undecan-2-one hydrochloride
• CAS: 1452809-30-1
• 化学式: C₃₀H₃₄N₂O*ClH
• 分子量: 475.074
• InChiKey: UEKZZKVTUJOAAJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.12
• 重原子数：
  34.0
• 可旋转键数：
  6.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  23.55
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  1,3,9-tribenzyl-1,9-diazaspiro[5.5]undecan-2-one hydrochloride 在 盐酸 、 lithium aluminium tetrahydride 、 palladium 10% on activated carbon 、 氢气 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 正丁醇 为溶剂， 40.0~100.0 ℃ 、101.33 kPa 条件下， 反应 28.0h， 生成 6-(3-Benzyl-1,9-diazaspiro[5.5]undecan-9-yl)-9H-purine
  参考文献：
  名称：

  Synthesis and evaluation of heteroaryl substituted diazaspirocycles as scaffolds to probe the ATP-binding site of protein kinases

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2013.07.021
• 作为产物：
  描述：

  2-苄基丙烯酸 在 titanium(IV) isopropylate 、 盐酸 、 4-二甲氨基吡啶 、 Hoveyda-Grubbs catalyst second generation 、 草酰氯 、 palladium 10% on activated carbon 、 氢气 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 20.0~40.0 ℃ 、101.33 kPa 条件下， 反应 97.0h， 生成 1,3,9-tribenzyl-1,9-diazaspiro[5.5]undecan-2-one hydrochloride
  参考文献：
  名称：

  Synthesis and evaluation of heteroaryl substituted diazaspirocycles as scaffolds to probe the ATP-binding site of protein kinases

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2013.07.021