methyl pyrazinylketone p-trifluromethylbenzoyl hydrazone

• 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: methyl pyrazinylketone p-trifluromethylbenzoyl hydrazone
• 英文别名: Methyl pyrazinylketone p-trifluoromethylbenzoyl hydrazone；N-[(E)-1-pyrazin-2-ylethylideneamino]-4-(trifluoromethyl)benzamide
• 化学式: C₁₄H₁₁F₃N₄O
• 分子量: 308.263
• InChiKey: JKWJCTNCHPWHEJ-AWQFTUOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  67.2
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-乙酰基吡嗪 、 4-(三氟甲基)亚苯基肼 在 盐酸 作用下， 以 乙醇 为溶剂， 以78%的产率得到methyl pyrazinylketone p-trifluromethylbenzoyl hydrazone
  参考文献：
  名称：

  Structure–Activity Relationships of Novel Iron Chelators for the Treatment of Iron Overload Disease: The Methyl Pyrazinylketone Isonicotinoyl Hydrazone Series

  摘要：

  The design of novel Fe chelators with high Fe mobilization efficacy and low toxicity remains an important priority for the treatment of Fe overload disease. We have designed and synthesized the novel methyl pyrazinylketone isonicotinoyl hydrazone (HMPIH) analogs based on previously investigated aroylhydrazone chelators. The HMPIH series demonstrated high Fe mobilization efficacy from cells and showed limited to moderate antiproliferative activity. Importantly, this novel series demonstrated irreversible electrochemistry, which was attributed to the electron-withdrawing effects of the noncoordinating pyrazine N-atom. The latter functionality played a major role in forming redox-inactive complexes that prevent reactive oxygen species generation. In fact, the Fe complexes of the HMPIH series prevented the oxidation of ascorbate and hydroxylation of benzoate. We determined that the incorporation of electron-withdrawing groups is an important feature in the design of N,N,O-aroylhydrazones as candidate drugs for the treatment of Fe overload disease.

  DOI：

  10.1021/jm7012562

文献信息

• Structure–Activity Relationships of Novel Iron Chelators for the Treatment of Iron Overload Disease: The Methyl Pyrazinylketone Isonicotinoyl Hydrazone Series
  作者：Danuta S. Kalinowski、Philip C. Sharpe、Paul V. Bernhardt、Des R. Richardson

  DOI：10.1021/jm7012562

  日期：2008.1.1

  The design of novel Fe chelators with high Fe mobilization efficacy and low toxicity remains an important priority for the treatment of Fe overload disease. We have designed and synthesized the novel methyl pyrazinylketone isonicotinoyl hydrazone (HMPIH) analogs based on previously investigated aroylhydrazone chelators. The HMPIH series demonstrated high Fe mobilization efficacy from cells and showed limited to moderate antiproliferative activity. Importantly, this novel series demonstrated irreversible electrochemistry, which was attributed to the electron-withdrawing effects of the noncoordinating pyrazine N-atom. The latter functionality played a major role in forming redox-inactive complexes that prevent reactive oxygen species generation. In fact, the Fe complexes of the HMPIH series prevented the oxidation of ascorbate and hydroxylation of benzoate. We determined that the incorporation of electron-withdrawing groups is an important feature in the design of N,N,O-aroylhydrazones as candidate drugs for the treatment of Fe overload disease.