1-(4-(benzyloxy)benzyl)piperazine | 523980-10-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-(4-(benzyloxy)benzyl)piperazine
• 英文别名: 4-(4-benzyloxy)benzylpiperazine；1-[(4-phenylmethoxyphenyl)methyl]piperazine
• CAS: 523980-10-1
• 化学式: C₁₈H₂₂N₂O
• 分子量: 282.385
• InChiKey: YZRJTYFUWXERTI-UHFFFAOYSA-N

物化性质

• 沸点：
  425.9±35.0 °C(Predicted)
• 密度：
  1.100±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  24.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(4-(benzyloxy)benzyl)piperazine 在 盐酸 、 碳酸氢钠 、 肼 作用下， 以 乙二醇乙醚 、 乙醇 、 水 、 丙酮 为溶剂， 生成 2-(4-(4-(benzyloxy)benzyl)piperazin-1-yl)-N'-(3,5-di-tert-butyl-2-hydroxybenzylidene)acetohydrazide
  参考文献：
  名称：

  Parallel Synthesis and Biological Evaluation of 837 Analogues of Procaspase-Activating Compound 1 (PAC-1)

  摘要：

  Procaspase-Activating Compound 1 (PAC-1) is an ortho-hydroxy N-acyl hydrazone that enhances the enzymatic activity of procaspase-3 in vitro and induces apoptosis in cancer cells. An analogue of PAC-1, called S-PAC-1, was evaluated in a veterinary clinical trial in pet dogs with lymphoma and found to have considerable potential as an anticancer agent. With the goal of identifying more potent compounds in this promising class of experimental therapeutics, a combinatorial library based on PAC-1 was created, and the compounds were evaluated for their ability to induce death of cancer cells in culture. For library construction, 31 hydrazides were condensed in parallel with 27 aldehydes to create 837 PAC-1 analogues, with an average purity of 91%. The compounds were evaluated for their ability to induce apoptosis in cancer cells, and through this work, six compounds were discovered to be substantially more potent than PAC-1 and S-PAC-1. These six hits were further evaluated for their ability to relieve zinc-mediated inhibition of procaspase-3 in vitro. In general, the newly identified hit compounds are two- to four-fold more potent than PAC-1 and S-PAC-1 in cell culture, and thus have promise as experimental therapeutics for treatment of the many cancers that have elevated expression levels of procaspase-3.

  DOI：

  10.1021/co2001372
• 作为产物：
  描述：

  4-苄氧基溴苄 在 盐酸 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 28.25h， 生成 1-(4-(benzyloxy)benzyl)piperazine
  参考文献：
  名称：

  Discovery libraries targeting the major enzyme classes: The serine hydrolases

  摘要：

  Two libraries of modestly reactive ureas containing either electron-deficient acyl anilines or acyl pyrazoles were prepared and are reported as screening libraries for candidate serine hydrolase inhibitors. Within each library is a small but powerful subset of compounds that serve as a chemotype fragment screening library capable of subsequent structural diversification. Elaboration of the pyrazole-based ureas provided remarkably potent irreversible inhibitors of fatty acid amide hydrolase (FAAH, apparent Ki=100-200 pM) complementary to those previously disclosed enlisting electron-deficient aniline-based ureas.

  DOI：

  10.1016/j.bmcl.2014.06.063

文献信息

• PROCASPASE-ACTIVATING COMPOUNDS AND COMPOSITIONS
  申请人：The Board of Trustees of the University of Illinoi

  公开号：US20130096133A1

  公开（公告）日：2013-04-18

  The invention provides compounds and compositions useful for the modulation of certain enzymes. The compounds and compositions can induce of cell death, particularly cancer cell death. The invention also provides methods for the synthesis and use of the compounds and compositions, including the use of compounds and compositions in therapy for the treatment of cancer and selective induction of apoptosis in cells.

  这项发明提供了用于调节某些酶的化合物和组合物。这些化合物和组合物可以诱导细胞死亡，特别是癌细胞死亡。该发明还提供了合成和使用这些化合物和组合物的方法，包括在治疗癌症和选择性诱导细胞凋亡中使用这些化合物和组合物的方法。
• N-Acyl pyrazoles: Effective and tunable inhibitors of serine hydrolases
  作者：Katerina Otrubova、Shreyosree Chatterjee、Srijana Ghimire、Benjamin F. Cravatt、Dale L. Boger

  DOI：10.1016/j.bmc.2019.03.020

  日期：2019.4

  (urea > carbamate > amide) and the pyrazole C4 substituent (CN > H > Me). It was further demonstrated that the acyl chain of the N-acyl pyrazole ureas can be used to tailor the potency and selectivity of the inhibitor class to a targeted serine hydrolase. Thus, elaboration of the acyl chain of pyrazole-based ureas provided remarkably potent, irreversible inhibitors of fatty acid amide hydrolase (FAAH

  研究了一系列N-酰基吡唑作为候选的丝氨酸水解酶抑制剂，其中不仅可以通过酰基的性质来调节活性位点的酰化反应性和吡唑的离去基能力（反应性：酰胺>氨基甲酸酯>尿素） ，也可以通过吡唑C4取代为吸电子或供电子的取代基。它们对酶抑制活性的影响显示出显着效果，并且随着显着改变反应的羰基（脲>氨基甲酸酯>酰胺）和吡唑C4取代基（CN> H> Me）的性质，其活性显着提高。进一步证明，N-酰基吡唑脲的酰基链可用于调节抑制剂类别对靶向的丝氨酸水解酶的效力和选择性。因此，
• Procaspase-activating compounds and compositions
  申请人：The Board of Trustees of the University of Illinois

  公开号：US08916705B2

  公开（公告）日：2014-12-23

  The invention provides compounds and compositions useful for the modulation of certain enzymes. The compounds and compositions can induce of cell death, particularly cancer cell death. The invention also provides methods for the synthesis and use of the compounds and compositions, including the use of compounds and compositions in therapy for the treatment of cancer and selective induction of apoptosis in cells.

  本发明提供了一种可用于调节某些酶的化合物和组合物。这些化合物和组合物可以诱导细胞死亡，特别是癌细胞死亡。本发明还提供了合成和使用这些化合物和组合物的方法，包括在治疗癌症和选择性诱导细胞凋亡方面使用这些化合物和组合物的方法。
• PROCASPASE-ACTIVATING COMPOUNDS AND METHODS
  申请人：The Board of Trustees of the University of Illinois

  公开号：US20150231132A1

  公开（公告）日：2015-08-20

  The invention provides compounds and compositions useful for the modulation of certain enzymes. The compounds and compositions can induce of cell death, particularly cancer cell death. The invention also provides methods for the synthesis and use of the compounds and compositions, including the use of compounds and compositions in therapy for the treatment of cancer and selective induction of apoptosis in cells.

  本发明提供了用于调节某些酶的化合物和组合物。这些化合物和组合物可以诱导细胞死亡，特别是癌细胞死亡。本发明还提供了化合物和组合物的合成和使用方法，包括在治疗癌症和选择性诱导细胞凋亡中使用化合物和组合物的方法。
• Procaspase-activating compounds and methods
  申请人：The Board of Trustees of the University of Illinois

  公开号：US10022371B2

  公开（公告）日：2018-07-17

  The invention provides compounds and compositions useful for the modulation of certain enzymes. The compounds and compositions can induce of cell death, particularly cancer cell death. The invention also provides methods for the synthesis and use of the compounds and compositions, including the use of compounds and compositions in therapy for the treatment of cancer and selective induction of apoptosis in cells.

  本发明提供了可用于调节某些酶的化合物和组合物。这些化合物和组合物可以诱导细胞死亡，特别是癌细胞死亡。本发明还提供了合成和使用这些化合物和组合物的方法，包括将化合物和组合物用于治疗癌症和选择性诱导细胞凋亡。