tert-butyl 4-(pyridin-4-ylcarbamoyl)piperidine-1-carboxylate | 204574-40-3

• 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: tert-butyl 4-(pyridin-4-ylcarbamoyl)piperidine-1-carboxylate
• CAS: 204574-40-3
• 化学式: C₁₆H₂₃N₃O₃
• 分子量: 305.377
• InChiKey: ZRJIVKUVYZIQNN-UHFFFAOYSA-N

物化性质

• 沸点：
  497.1±35.0 °C(Predicted)
• 密度：
  1.190±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  71.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(pyridin-4-ylcarbamoyl)piperidine-1-carboxylate 在 碳酸氢钠 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 三氟乙酸 、 lithium hydroxide 作用下， 以 二氯甲烷 、 水 、 丙酮 为溶剂， 反应 8.0h， 生成 N¹-((S)-4-methyl-1-(((S)-1-(((S)-4-methyl-1-((R)-2-methyloxiran-2-yl)-1-oxopentan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)amino)-1-oxopentan-2-yl)-N⁴-(pyridin-4-yl)piperidine-1,4-dicarboxamide
  参考文献：
  名称：

  Covalent docking modelling-based discovery of tripeptidyl epoxyketone proteasome inhibitors composed of aliphatic-heterocycles

  摘要：

  The potential of specific proteasome inhibitors to act as anti-cancer agents has attracted intensive investigations. The proteasome can be covalently inhibited by epoxyketone derivatives via a two-step reaction. Several computational approaches have been developed to mimic the covalent binding event. Compound 1 composed of a six-membered heterocyclic ring was designed by using covalent docking. With a possible different binding mode from the clinical compound Carfilzomib, it occupied the 55 pocket of 20S proteasome and showed favorable inhibitory activity. Subsequently optimization and evaluation were taken place. Among these compounds, 11h demonstrated extraordinary in vitro inhibitory activity and selectivity, and good in vivo proteasome inhibitory activity, a favorable pharmacokinetic profile and xenograft tumor inhibition. The possible binding pattern of compound 11h against proteasome was further fully explored via calculations, providing a theoretical basis for finding potent proteasome inhibitors. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.12.064
• 作为产物：
  描述：

  4-(叔丁氧羰基氨基)吡啶 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 tert-butyl 4-(pyridin-4-ylcarbamoyl)piperidine-1-carboxylate
  参考文献：
  名称：

  治疗中枢神经系统退行性疾病或脑肿瘤的化 合物及其应用

  摘要：

  本发明涉及治疗中枢系统退行性疾病或脑肿瘤的化合物、药物组合物及其应用，该化合物具有式（）的结构，这些化合物可作为具有抗氧化作用的SGK1和JNK的双靶点抑制剂，而被制成适当的药物剂型用于中枢神经退行性疾病、脑肿瘤的治疗。式（）。

  公开号：

  CN106279136B

文献信息

• Practical preparation of challenging amides from non-nucleophilic amines and esters under flow conditions
  作者：Johannes L. Vrijdag、Francisca Delgado、Nerea Alonso、Wim M. De Borggraeve、Natalia Pérez-Macias、Jesus Alcázar

  DOI：10.1039/c4cc07129h

  日期：——

  Preparation of amides from low nucleophilic heterocyclic amines is achieved in 2 minutes under mild conditions.

  从低亲核杂环胺制备酰胺在温和条件下可以在2分钟内完成。
• NOVEL TRICYCLIC PIPERIDINYL COMPOUNDS USEFUL AS INHIBITORS OF FARNESYL-PROTEIN TRANSFERASE
  申请人：SCHERING CORPORATION

  公开号：EP0931078B1

  公开（公告）日：2006-11-15
• Covalent docking modelling-based discovery of tripeptidyl epoxyketone proteasome inhibitors composed of aliphatic-heterocycles
  作者：Xiao-Wu Dong、Jian-Kang Zhang、Lei Xu、Jin-Xin Che、Gang Cheng、Xiao-Bei Hu、Li Sheng、An-Hui Gao、Jia Li、Tao Liu、Yong-Zhou Hu、Yu-Bo Zhou

  DOI：10.1016/j.ejmech.2018.12.064

  日期：2019.2

  The potential of specific proteasome inhibitors to act as anti-cancer agents has attracted intensive investigations. The proteasome can be covalently inhibited by epoxyketone derivatives via a two-step reaction. Several computational approaches have been developed to mimic the covalent binding event. Compound 1 composed of a six-membered heterocyclic ring was designed by using covalent docking. With a possible different binding mode from the clinical compound Carfilzomib, it occupied the 55 pocket of 20S proteasome and showed favorable inhibitory activity. Subsequently optimization and evaluation were taken place. Among these compounds, 11h demonstrated extraordinary in vitro inhibitory activity and selectivity, and good in vivo proteasome inhibitory activity, a favorable pharmacokinetic profile and xenograft tumor inhibition. The possible binding pattern of compound 11h against proteasome was further fully explored via calculations, providing a theoretical basis for finding potent proteasome inhibitors. (C) 2018 Elsevier Masson SAS. All rights reserved.
• 治疗中枢神经系统退行性疾病或脑肿瘤的化 合物及其应用
  申请人：中山大学

  公开号：CN106279136B

  公开（公告）日：2019-06-21

  本发明涉及治疗中枢系统退行性疾病或脑肿瘤的化合物、药物组合物及其应用，该化合物具有式（）的结构，这些化合物可作为具有抗氧化作用的SGK1和JNK的双靶点抑制剂，而被制成适当的药物剂型用于中枢神经退行性疾病、脑肿瘤的治疗。式（）。