(E)-2-(4-benzylpiperazin-1-yl)-N'-((3-hydroxy-5-(hydroxymethyl)-2-methylpyridin-4-yl)methylene)acetohydrazide | 1449679-59-7

• 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: (E)-2-(4-benzylpiperazin-1-yl)-N'-((3-hydroxy-5-(hydroxymethyl)-2-methylpyridin-4-yl)methylene)acetohydrazide
• 英文别名: 2-(4-benzylpiperazin-1-yl)-N-[(E)-[3-hydroxy-5-(hydroxymethyl)-2-methylpyridin-4-yl]methylideneamino]acetamide
• CAS: 1449679-59-7
• 化学式: C₂₁H₂₇N₅O₃
• 分子量: 397.477
• InChiKey: QFPVDYVNRNGXRQ-FSJBWODESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  101
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  1-苄基-4-(乙氧基羰基甲基)哌嗪 在 sodium carbonate 、 一水合肼 作用下， 以 乙醇 、 水 为溶剂， 反应 1.5h， 生成 (E)-2-(4-benzylpiperazin-1-yl)-N'-((3-hydroxy-5-(hydroxymethyl)-2-methylpyridin-4-yl)methylene)acetohydrazide
  参考文献：
  名称：

  Synthesis and initial in vitro biological evaluation of two new zinc-chelating compounds: Comparison with TPEN and PAC-1

  摘要：

  The lipophilic, cell-penetrating zinc chelator N,N,N',N',-tetrakis(2-pyridylmethyl) ethylenediamine (TPEN, 1) and the zinc chelating procaspase-activating compound PAC-1 (2) both have been reported to induce apoptosis in various cell types. The relationship between apoptosis-inducing ability and zinc affinity (K-d), have been investigated with two new model compounds, ZnA-DPA (3) and ZnA-Pyr (4), and compared to that of TPEN and PAC-1. The zinc-chelating o-hydroxybenzylidene moiety in PAC-1 was replaced with a 2,2'-dipicoylamine (DPA) unit (ZnA-DPA, 3) and a 4-pyridoxyl unit (ZnA-Pyr, 4), rendering an order of zinc affinity TPEN > ZnA-Pyr > ZnA-DPA > PAC-1. The compounds were incubated with the rat pheochromocytoma cell line PC12 and cell death was measured in combination with ZnSO4, a caspase-3 inhibitor, or a ROS scavenger. The model compounds ZnA-DPA (3) and ZnA-Pyr (4) induced cell death at higher concentrations as compared to PAC-1 and TPEN, reflecting differences in lipophilicity and thereby cell-penetrating ability. Addition of ZnSO4 reduced cell death induced by ZnA-Pyr (4) more than for ZnA-DPA (3). The ability to induce cell death could be reversed for all compounds using a caspase-3-inhibitor, and most so for TPEN (1) and ZnA-Pyr (4). Reactive oxygen species (ROS), as monitored using dihydro-rhodamine (DHR), were involved in cell death induced by all compounds. These results indicate that the Zn-chelators ZnA-DPA (3) and ZnA-Pyr (4) exercise their apoptosis-inducing effect by mechanisms similar to TPEN (1) and PAC-1 (2), by chelation of zinc, caspase-3 activation, and RoS production. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.06.037