8-propyl-1,3,8-triaza-spiro[4.5]decane-2,4-dione | 501127-85-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: 8-propyl-1,3,8-triaza-spiro[4.5]decane-2,4-dione
• 英文别名: 8-propyl-1,3,8-triazaspiro[4.5]decane-2,4-dione；4-oxo-8-propyl-1,3-diaza-8-azoniaspiro[4.5]dec-1-en-2-olate
• CAS: 501127-85-1
• 化学式: C₁₀H₁₇N₃O₂
• 分子量: 211.264
• InChiKey: CITFTSZERJEKKN-UHFFFAOYSA-N

物化性质

• 密度：
  1.22±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  61.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-bromomethyl-7-(2,2-dimethyl-propyl)-7H-pyrrolo[2,3-d]pyrimidine-2-carbonitrile 、 8-propyl-1,3,8-triaza-spiro[4.5]decane-2,4-dione 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 以5.87 g的产率得到7-(2,2-dimethyl-propyl)-6-(2,4-dioxo-8-propyl-1,3,8-triaza-spiro[4.5]dec-3-ylmethyl)-7H-pyrrolo[2,3-d]pyrimidine-2-carbonitrile
  参考文献：
  名称：

  Effect of Cathepsin K Inhibitors on Bone Resorption

  摘要：

  Oil the basis of the pyrrolopyrimidine core structure that was previously discovered, cathepsin K inhibitors having a spiro amine at the P3 have been explored to enhance the target, bone marrow, tissue distribution. Several spiro structures were identified with improved distribution toward bone marrow. The representative inhibitor 7 of this series revealed in vivo reduction in C-terminal telopeptide of type I collagen in rats and monkeys.

  DOI：

  10.1021/jm800626a
• 作为产物：
  描述：

  N-丙基-4-哌啶酮 、 sodium cyanide 在 碳酸氢铵 作用下， 以 甲醇 、 水 为溶剂， 生成 8-propyl-1,3,8-triaza-spiro[4.5]decane-2,4-dione
  参考文献：
  名称：

  Effect of Cathepsin K Inhibitors on Bone Resorption

  摘要：

  Oil the basis of the pyrrolopyrimidine core structure that was previously discovered, cathepsin K inhibitors having a spiro amine at the P3 have been explored to enhance the target, bone marrow, tissue distribution. Several spiro structures were identified with improved distribution toward bone marrow. The representative inhibitor 7 of this series revealed in vivo reduction in C-terminal telopeptide of type I collagen in rats and monkeys.

  DOI：

  10.1021/jm800626a

文献信息

• Microwave-assisted synthesis of functionalized spirohydantoins as 3-D privileged fragments for scouting the chemical space
  作者：Hugues Prevet、Marion Flipo、Pascal Roussel、Benoit Deprez、Nicolas Willand

  DOI：10.1016/j.tetlet.2016.05.065

  日期：2016.6

  protein–protein interactions, it is required to enrich current fragment libraries with new and original 3D privileged fragments. Our goal was to develop a rapid microwave-assisted synthesis of 27 new privileged spirohydantoin fragments. Among them 24 compounds showed a high water solubility. These molecules were plotted according to the normalized principal moments of inertia of their minimized conformers

  基于片段的药物设计已成功应用于大量蛋白质，但是，为了将这一概念扩展到最苛刻的目标，例如蛋白质与蛋白质的相互作用，需要使用新的和原始的3D特权丰富当前的片段库碎片。我们的目标是开发微波辅助快速合成27个新的螺乙内酰脲片段的方法。其中24种化合物显示出高水溶性。这些分子是根据其最小化构象异构体的归一化主要惯性矩绘制的，并且大多数化合物都倾向于占据三角形图中人口不足的区域。最后，我们证明了乙内酰脲环可以选择性地为N-单烷基化提供了快速官能化的进一步途径。
• Pyrrolo pyrimidines as agents for the inhibition of cystein proteases
  申请人：Betschart Claudia

  公开号：US20050054851A1

  公开（公告）日：2005-03-10

  The invention provides compounds of Formula I or a pharmaceutically acceptable salt or ester thereof wherein the symbols have meaning as defined, which are inhibitors of cathepsin K and find use pharmaceutically for treatment of diseases and medical conditions in which cathepsin K is implicated, e.g. various disorders including inflammation, rheumatoid arthritis, osteoarthritis, osteoporosis and tumors.

  本发明提供了I式化合物或其药学上可接受的盐或酯，其中符号的含义如定义所述，它们是猫hepsin K的抑制剂，并在药学上用于治疗猫hepsin K参与的疾病和医疗情况，例如各种疾病，包括炎症、类风湿性关节炎、骨关节炎、骨质疏松和肿瘤。
• Pyrrolo Pyrimidines as Agents for the Inhibition of Cystein Proteases
  申请人：Betschart Claudia

  公开号：US20090054467A1

  公开（公告）日：2009-02-26

  The invention provides compounds of Formula I or a pharmaceutically acceptable salt or ester thereof wherein the symbols have meaning as defined, which are inhibitors of cathepsin K and find use pharmaceutically for treatment of diseases and medical conditions in which cathepsin K is implicated, e.g. various disorders including inflammation, rheumatoid arthritis, osteoarthritis, osteoporosis and tumors.

  本发明提供了公式I的化合物，或其药理学上可接受的盐或酯，其中符号具有定义的含义，这些化合物是卡特普西林K的抑制剂，并在药学上用于治疗与卡特普西林K有关的疾病和医疗条件，例如各种疾病，包括炎症，类风湿性关节炎，骨关节炎，骨质疏松和肿瘤。
• Novel scaffold for cathepsin K inhibitors
  作者：Naoki Teno、Takahiro Miyake、Takeru Ehara、Osamu Irie、Junichi Sakaki、Osamu Ohmori、Hiroki Gunji、Naoko Matsuura、Keiichi Masuya、Yuko Hitomi、Kazuhiko Nonomura、Miyuki Horiuchi、Keigo Gohda、Atsuko Iwasaki、Ichiro Umemura、Sachiyo Tada、Motohiko Kometani、Genji Iwasaki、Sandra W. Cowan-Jacob、Martin Missbach、René Lattmann、Claudia Betschart

  DOI：10.1016/j.bmcl.2007.09.047

  日期：2007.11

  Pyrrolopyrimidine, a novel scaffold, allows to adjust interactions within the S3 subsite of cathepsin K. The core intermediate 10 facilitated the P3 optimization and identified highly potent and selective cathepsin K inhibitors 11-20.
• PYRROLO PYRIMIDINES AS AGENTS FOR THE INHIBITION OF CYSTEIN PROTEASES
  申请人：Novartis AG

  公开号：EP1423391A1

  公开（公告）日：2004-06-02