(E)-2-(4-fluorobenzylcarbamoyl)-3-phenylacrylic acid | 934619-06-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (E)-2-(4-fluorobenzylcarbamoyl)-3-phenylacrylic acid
• 英文别名: 2-(4-fluorobenzylcarbamoyl)-3-phenylacrylic acid；(E)-2-[(4-fluorophenyl)methylcarbamoyl]-3-phenylprop-2-enoic acid
• CAS: 934619-06-4
• 化学式: C₁₇H₁₄FNO₃
• 分子量: 299.301
• InChiKey: LKDMAKQGJUSRJK-XNTDXEJSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  66.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (E)-2-(4-fluorobenzylcarbamoyl)-3-phenylacrylic acid 在 三异丙基硅烷 、 氯甲酸乙酯 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.58h， 生成 N-(4-fluorobenzyl)-N'-hydroxy-2-[1-phenylmeth-(E)-ylidene]malonamide
  参考文献：
  名称：

  Novel Selective Inhibitors of the Zinc Plasmodial Aminopeptidase PfA-M1 as Potential Antimalarial Agents

  摘要：

  Proteases that are expressed during the erythocytic stage of Plasmodium falciparum are newly explored drug targets for the treatment of malaria. We report here the discovery of potent inhibitors of PfA-M1, a metallo-aminopeptidase of the parasite. These compounds are based on a malonic hydroxamic template and present a very good selectivity toward neutral aminopeptidase (APN-CD13), a related protease in mammals. Structure-activity relationships in these series are described. Further optimization of the best inhibitor yielded a nanomolar, selective inhibitor of PfA-M1. This inhibitor displays good physicochemical and pharmacokinetic properties and a promising antimalarial activity.

  DOI：

  10.1021/jm061169b
• 作为产物：
  描述：

  (Z)-2-(ethoxycarbonyl)-3-phenylacrylic acid 在 lithium hydroxide 、 氯甲酸乙酯 、 三乙胺 、 sodium chloride 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 乙酸乙酯 为溶剂， 反应 1.5h， 生成 (E)-2-(4-fluorobenzylcarbamoyl)-3-phenylacrylic acid
  参考文献：
  名称：

  Novel Selective Inhibitors of the Zinc Plasmodial Aminopeptidase PfA-M1 as Potential Antimalarial Agents

  摘要：

  Proteases that are expressed during the erythocytic stage of Plasmodium falciparum are newly explored drug targets for the treatment of malaria. We report here the discovery of potent inhibitors of PfA-M1, a metallo-aminopeptidase of the parasite. These compounds are based on a malonic hydroxamic template and present a very good selectivity toward neutral aminopeptidase (APN-CD13), a related protease in mammals. Structure-activity relationships in these series are described. Further optimization of the best inhibitor yielded a nanomolar, selective inhibitor of PfA-M1. This inhibitor displays good physicochemical and pharmacokinetic properties and a promising antimalarial activity.

  DOI：

  10.1021/jm061169b

文献信息

• Hydroxamates: Relationships between Structure and Plasma Stability
  作者：Marion Flipo、Julie Charton、Akila Hocine、Sandrine Dassonneville、Benoit Deprez、Rebecca Deprez-Poulain

  DOI：10.1021/jm900648x

  日期：2009.11.12

  display nanomolar activities against metalloproteases, only three hydroxamates have reached the market, among which is the HDAC inhibitor vorinostat. Failures in development are generally attributed to lack of selectivity, toxicity, or poor stability. To help medicinal chemists with respect to plasma stability, we have performed the first and preliminary study on structure−plasma stability for hydroxamates

  异羟肟酸酯是用于化学生物学的有价值的工具，也是用于药物化学的有趣线索。尽管许多异羟肟酸酯显示出对金属蛋白酶的纳摩尔活性，但只有三种异羟肟酸酯进入市场，其中包括HDAC抑制剂伏立诺他。开发失败通常归因于缺乏选择性，毒性或稳定性差。为了帮助药用化学家进行血浆稳定性方面的研究，我们对异羟肟酸酯的结构-血浆稳定性进行了首次和初步研究。我们定义一些结构规则，以预测或改善临床前阶段的血浆稳定性。
• Novel Selective Inhibitors of the Zinc Plasmodial Aminopeptidase PfA-M1 as Potential Antimalarial Agents
  作者：Marion Flipo、Terence Beghyn、Virginie Leroux、Isabelle Florent、Benoit P. Deprez、Rebecca F. Deprez-Poulain

  DOI：10.1021/jm061169b

  日期：2007.3.1

  Proteases that are expressed during the erythocytic stage of Plasmodium falciparum are newly explored drug targets for the treatment of malaria. We report here the discovery of potent inhibitors of PfA-M1, a metallo-aminopeptidase of the parasite. These compounds are based on a malonic hydroxamic template and present a very good selectivity toward neutral aminopeptidase (APN-CD13), a related protease in mammals. Structure-activity relationships in these series are described. Further optimization of the best inhibitor yielded a nanomolar, selective inhibitor of PfA-M1. This inhibitor displays good physicochemical and pharmacokinetic properties and a promising antimalarial activity.