piperazin-1-yl-pyrazin-2-yl-methanone | 866863-62-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: piperazin-1-yl-pyrazin-2-yl-methanone
• 英文别名: 4-(pyrazin-2-ylcarbonyl)piperazin；5-(piperazine-1-carbonyl)pyrazine；4-(pyrazine-2-carbonyl)piperazin；1-(pyrazin-2-oyl)piperazine；2-(Piperazine-1-carbonyl)pyrazine；piperazin-1-yl(pyrazin-2-yl)methanone
• CAS: 866863-62-9
• 化学式: C₉H₁₂N₄O
• mdl: MFCD04973505
• 分子量: 192.22
• InChiKey: XYIUHUJSAYIVAS-UHFFFAOYSA-N

物化性质

• 沸点：
  377.4±42.0 °C(Predicted)
• 密度：
  1.224±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.444
• 拓扑面积：
  58.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  piperazin-1-yl-pyrazin-2-yl-methanone 在 碳酸氢钠 、 N,N-二异丙基乙胺 、 lithium hydroxide 作用下， 以 二氯甲烷 、 水 、 丙酮 为溶剂， 反应 3.5h， 生成
  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：

  tert-butyl 4-(pyrazine-2-carbonyl)piperazine-1-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 piperazin-1-yl-pyrazin-2-yl-methanone
  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

文献信息

• [EN] TRICYCLIC PYRAZOLE KINASE INHIBITORS<br/>[FR] INHIBITEURS DE KINASES A BASE DE TYRAZOLES TRICYCLIQUES
  申请人：ABBOTT LAB

  公开号：WO2005095387A1

  公开（公告）日：2005-10-13

  Compounds of the present invention are useful for inhibiting protein tyrosine kinases. Also disclosed are methods of making the compounds, compositions containing the compounds, and methods of treatment using the compounds.

  本发明的化合物对抑制蛋白酪氨酸激酶具有用处。还公开了制备这些化合物的方法、含有这些化合物的组合物以及使用这些化合物进行治疗的方法。
• TRIPEPTIDE EPOXYKETONE COMPOUND CONSTRUCTED BY HETEROCYCLE AND PREPARATION METHOD AND USE THEREOF
  申请人：ZHEJIANG UNIVERSITY

  公开号：US20170022250A1

  公开（公告）日：2017-01-26

  Disclosed are a tripeptide epoxyketone compound, a preparation method thereof, and a use thereof in the preparation of anti-tumor drugs.

  公开了一种三肽环氧酮化合物，其制备方法及其在抗肿瘤药物制备中的用途。
• Tricyclic pyrazole kinase inhibitors
  申请人：Arnold D. Lee

  公开号：US20060014816A1

  公开（公告）日：2006-01-19

  Compounds of the present invention are useful for inhibiting protein tyrosine kinases. Also disclosed are methods of making the compounds, compositions containing the compounds, and methods of treatment using the compounds.

  本发明的化合物可用于抑制蛋白酪氨酸激酶。还公开了制备该化合物的方法，含有该化合物的组合物，以及使用该化合物的治疗方法。
• Dipeptidyl peptidase-4 inhibitor with β-amino amide scaffold: Synthesis, SAR and biological evaluation
  作者：Heung Jae Kim、Woo Young Kwak、Jong Pil Min、Si Young Sung、Ha Dong Kim、Mi Kyung Kim、Hae Sun Kim、Kyung Jin Park、Moon Ho Son、Soon Hoe Kim、Bong Jin Lee

  DOI：10.1016/j.bmcl.2012.07.019

  日期：2012.9

  Inhibitors of dipeptidyl peptidase-4 (DPP4) have been shown to be effective treatments for type 2 diabetes. Several series of beta-amino amide containing piperazine derivatives have been prepared and evaluated as a inhibitor of DPP4. Finally compound 5m was selected for further evaluation. (C) 2012 Elsevier Ltd. All rights reserved.
• TRICYCLIC PYRAZOLE KINASE INHIBITORS
  申请人：ABBOTT LABORATORIES

  公开号：EP1740579A1

  公开（公告）日：2007-01-10