N'-(3-allyl-2-hydroxybenzylidene)-2-(4-(3-(azidomethyl)benzyl)piperazin-1-yl)acetohydrazide | 1187959-85-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: N'-(3-allyl-2-hydroxybenzylidene)-2-(4-(3-(azidomethyl)benzyl)piperazin-1-yl)acetohydrazide
• 英文别名: 2-[4-[[3-(azidomethyl)phenyl]methyl]piperazin-1-yl]-N-[(2-hydroxy-3-prop-2-enylphenyl)methylideneamino]acetamide
• CAS: 1187959-85-8
• 化学式: C₂₄H₂₉N₇O₂
• 分子量: 447.54
• InChiKey: IJHOYMSAQWYNLJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  33
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  82.5
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  APDye 350 Alkyne 、 N'-(3-allyl-2-hydroxybenzylidene)-2-(4-(3-(azidomethyl)benzyl)piperazin-1-yl)acetohydrazide 在 tetrakis(actonitrile)copper(I) hexafluorophosphate 、 silica gel 、 三[(1-苄基-1H-1,2,3-三唑-4-基)甲基]胺 作用下， 以 甲醇 、 水 、 叔丁醇 为溶剂， 反应 24.0h， 以2.4 mg的产率得到3-(2-((1-(3-((4-(2-(2-(3-allyl-2-hydroxybenzylidene)hydrazinyl)-2-oxoethyl)piperazin-1-yl)methyl)benzyl)-1H-1,2,3-triazol-4-yl)methylamino)-2-oxoethyl)-7-amino-4-methyl-2-oxo-2H-chromene-6-sulfonic acid
  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：

  3-烯丙基-2-羟基苯甲醛 、 2-(4-(3-(azidomethyl)benzyl)piperazin-1-yl)acetohydrazide 在 盐酸 作用下， 以 乙醇 、 水 为溶剂， 反应 15.0h， 以84%的产率得到N'-(3-allyl-2-hydroxybenzylidene)-2-(4-(3-(azidomethyl)benzyl)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

文献信息

• [EN] DESIGN, SYNTHESIS AND EVALUATION OF PROCASPASE ACTIVATING COMPOUNDS AS PERSONALIZED ANTI-CANCER DRUGS<br/>[FR] CONCEPTION, SYNTHÈSE ET ÉVALUATION DE COMPOSÉS ACTIVATEURS DE PROCASPASE EN TANT QUE MÉDICAMENTS ANTICANCÉREUX PERSONNALISÉS
  申请人：UNIV ILLINOIS

  公开号：WO2010091382A1

  公开（公告）日：2010-08-12

  Compositions and methods are disclosed in embodiments relating to induction of cell death such as in cancer cells. Compounds and related methods for synthesis and use thereof, including the use of compounds in therapy for the treatment of cancer and selective induction of apoptosis in cells are disclosed. Compounds are disclosed that have lower neurotoxicity effects than other compounds.

  本发明公开了涉及诱导细胞死亡（例如癌细胞）的组合物和方法。公开了用于合成和使用这些化合物的相关方法，包括在癌症治疗中使用化合物以及在细胞中选择性诱导凋亡。公开了具有比其他化合物更低神经毒性效应的化合物。