ethyl 2-(4-(3-nitrobenzyl)piperazin-1-yl)acetate | 314061-29-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: ethyl 2-(4-(3-nitrobenzyl)piperazin-1-yl)acetate
• 英文别名: Ethyl 2-(4-(3-nitrobenzyl)-1-piperazinyl)-acetate；Ethyl 2-[4-[(3-nitrophenyl)methyl]piperazin-1-yl]acetate
• CAS: 314061-29-5
• 化学式: C₁₅H₂₁N₃O₄
• 分子量: 307.349
• InChiKey: HOMQMUNYDNTBMW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  78.6
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl 2-(4-(3-nitrobenzyl)piperazin-1-yl)acetate 在 肼 作用下， 以 乙醇 为溶剂， 以82%的产率得到2-(4-(3-nitrobenzyl)piperazin-1-yl)acetohydrazide
  参考文献：
  名称：

  Procaspase-3 Activation as an Anti-Cancer Strategy: Structure−Activity Relationship of Procaspase-Activating Compound 1 (PAC-1) and Its Cellular Co-Localization with Caspase-3

  摘要：

  A goal of personalized medicine as applied to oncology is to identify compounds that exploit a defined molecular defect in a cancerous cell. A compound called procaspase-activating compound I (PAC-1) was reported that enhances the activity of procaspase-3 in vitro and induces apoptotic death in cancer cells in culture and in mouse xenograft models. Experimental evidence indicates that PAC-1 activates procaspase-3 in vitro through chelation of inhibitory zinc ions. Described herein is the synthesis and biological activity of a family of PAC-1 derivatives where key functional groups have been systematically altered. Analysis of these compounds reveals a strong correlation between the in vitro procaspase-3 activating effect and their ability to induce death in cancer cells in culture. Importantly, we also show that a fluorescently labeled version of PAC-1 co-localizes with sites of caspase-3 activity in cancer cells. The data presented herein further bolster the hypothesis that PAC-1 induces apoptosis in cancer cells through the direct activation of procaspase-3, has implications for the design and discovery of next-generation procaspase-3 activating compounds, and sheds light on the anti-apoptotic role of cellular zinc.

  DOI：

  10.1021/jm900722z
• 作为产物：
  描述：

  1-(3-硝基苄基)哌嗪 、 氯乙酸乙酯 在 碳酸氢钠 作用下， 以 丙酮 为溶剂， 以86%的产率得到ethyl 2-(4-(3-nitrobenzyl)piperazin-1-yl)acetate
  参考文献：
  名称：

  Procaspase-3 Activation as an Anti-Cancer Strategy: Structure−Activity Relationship of Procaspase-Activating Compound 1 (PAC-1) and Its Cellular Co-Localization with Caspase-3

  摘要：

  A goal of personalized medicine as applied to oncology is to identify compounds that exploit a defined molecular defect in a cancerous cell. A compound called procaspase-activating compound I (PAC-1) was reported that enhances the activity of procaspase-3 in vitro and induces apoptotic death in cancer cells in culture and in mouse xenograft models. Experimental evidence indicates that PAC-1 activates procaspase-3 in vitro through chelation of inhibitory zinc ions. Described herein is the synthesis and biological activity of a family of PAC-1 derivatives where key functional groups have been systematically altered. Analysis of these compounds reveals a strong correlation between the in vitro procaspase-3 activating effect and their ability to induce death in cancer cells in culture. Importantly, we also show that a fluorescently labeled version of PAC-1 co-localizes with sites of caspase-3 activity in cancer cells. The data presented herein further bolster the hypothesis that PAC-1 induces apoptosis in cancer cells through the direct activation of procaspase-3, has implications for the design and discovery of next-generation procaspase-3 activating compounds, and sheds light on the anti-apoptotic role of cellular zinc.

  DOI：

  10.1021/jm900722z

文献信息

• Novel benzimidazole derivatives and pharmaceutical compositions comprising these compounds
  申请人：——

  公开号：US20030055055A1

  公开（公告）日：2003-03-20

  The present invention relates to novel benzimidazole derivatives, pharmaceutical composition containing these compounds, and methods of treatment therewith. The compounds of the invention are useful in the treatment of central nervous system diseases and disorders, which are responsive to modulation of the GABA receptor complex, and in particular for inducing and maintaining anesthesia, sedation and muscle relaxation, as well as for combating febrile convulsions in children. The compounds of the invention may also be used by veterinarians.

  本发明涉及新型苯并咪唑衍生物，含有这些化合物的药物组合物，以及使用这些化合物进行治疗的方法。本发明的化合物在治疗对GABA受体复合物调节敏感的中枢神经系统疾病和紊乱方面具有用途，特别是用于诱导和维持麻醉、镇静和肌肉松弛，以及用于对抗儿童的热性惊厥。本发明的化合物也可以被兽医使用。
• BENZIMIDAZOLE DERIVATIVES AND PHARMACEUTICAL COMPOSITIONS COMPRISING THESE COMPOUNDS
  申请人：NEUROSEARCH A/S

  公开号：EP1194410A1

  公开（公告）日：2002-04-10
• US6649609B2
  申请人：——

  公开号：US6649609B2

  公开（公告）日：2003-11-18
• US6936613B2
  申请人：——

  公开号：US6936613B2

  公开（公告）日：2005-08-30
• [EN] NOVEL BENZIMIDAZOLE DERIVATIVES AND PHARMACEUTICAL COMPOSITIONS COMPRISING THESE COMPOUNDS<br/>[FR] NOUVEAUX DERIVES DE BENZIMIDAZOLE ET COMPOSITIONS PHARMACEUTIQUES COMPRENANT CES COMPOSES
  申请人：NEUROSEARCH AS

  公开号：WO2000078728A1

  公开（公告）日：2000-12-28

  The present invention relates to novel benzimidazole derivatives, pharmaceutical compositions containing these compounds, and methods of treatment therewith. The compounds of the invention are useful in the treatment of central nervous system diseases and disorders, which are responsive to modulation of the GABAA receptor complex, and in particular for inducing and maintaining anaesthesia, sedation and muscle relaxation, as well as for combating febrile convulsions in children. The compounds of the invention may also be used by veterinarians.