(2E,N',E)-3-{4-(E)-[3,7-Dimethylocta-2,6-dienyloxy]phenyl}-N'-[phthalazin-1-(2H)-ylidiene]acrylohydrazide | 1268515-44-1

• 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: (2E,N',E)-3-{4-(E)-[3,7-Dimethylocta-2,6-dienyloxy]phenyl}-N'-[phthalazin-1-(2H)-ylidiene]acrylohydrazide
• 英文别名: (E)-3-[4-[(2E)-3,7-dimethylocta-2,6-dienoxy]phenyl]-N-[(Z)-2H-phthalazin-1-ylideneamino]prop-2-enamide；(E)-3-[4-[(2E)-3,7-dimethylocta-2,6-dienoxy]phenyl]-N'-phthalazin-1-ylprop-2-enehydrazide
• CAS: 1268515-44-1
• 化学式: C₂₇H₃₀N₄O₂
• 分子量: 442.561
• InChiKey: NUPQHKPBYHREMI-HDNIMXTOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  33
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  76.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  methyl 4-hydroxycinnamate 在 水 、 potassium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 potassium iodide 作用下， 以 甲醇 、 二氯甲烷 、 丙酮 为溶剂， 反应 47.0h， 生成 (2E,N',E)-3-{4-(E)-[3,7-Dimethylocta-2,6-dienyloxy]phenyl}-N'-[phthalazin-1-(2H)-ylidiene]acrylohydrazide
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of New Cinnamic Derivatives as Antituberculosis Agents

  摘要：

  Tuberculosis, HIV coinfection with TB, emergence of multidrug-resistant TB, and extensively drug-resistant TB are the major causes of death from infectious diseases worldwide. Because no new drug has been introduced in the last several decades, new classes of molecules as anti-TB drugs are urgently needed. Herein, we report the synthesis and structure-activity relationships of a series of thioester, amide, hydrazide, and triazolophthalazine derivatives of 4-alkoxy cinnamic acid. Many compounds exhibited submicromolar minimum inhibitory concentrations against Mycobacterium tuberculosis strain (H(37)Rv). Interestingly, compound 13e, a 4-isopentenyloxycinnamyl triazolophthalazine derivative, was found to be 100-1800 times more active than isoniazid (INH) when tested for its ability to inhibit the growth of INH-resistant M. tuberculosis strains. The results also revealed that 13e does not interfere with mycolic acid biosynthesis, thereby pointing to a different mode of action and representing an attractive lead compound for the development of new anti-TB agents.

  DOI：

  10.1021/jm101510d

文献信息

• Design, Synthesis, and Biological Evaluation of New Cinnamic Derivatives as Antituberculosis Agents
  作者：Prithwiraj De、Georges Koumba Yoya、Patricia Constant、Florence Bedos-Belval、Hubert Duran、Nathalie Saffon、Mamadou Daffé、Michel Baltas

  DOI：10.1021/jm101510d

  日期：2011.3.10

  Tuberculosis, HIV coinfection with TB, emergence of multidrug-resistant TB, and extensively drug-resistant TB are the major causes of death from infectious diseases worldwide. Because no new drug has been introduced in the last several decades, new classes of molecules as anti-TB drugs are urgently needed. Herein, we report the synthesis and structure-activity relationships of a series of thioester, amide, hydrazide, and triazolophthalazine derivatives of 4-alkoxy cinnamic acid. Many compounds exhibited submicromolar minimum inhibitory concentrations against Mycobacterium tuberculosis strain (H(37)Rv). Interestingly, compound 13e, a 4-isopentenyloxycinnamyl triazolophthalazine derivative, was found to be 100-1800 times more active than isoniazid (INH) when tested for its ability to inhibit the growth of INH-resistant M. tuberculosis strains. The results also revealed that 13e does not interfere with mycolic acid biosynthesis, thereby pointing to a different mode of action and representing an attractive lead compound for the development of new anti-TB agents.