(E)-3-(4-(2',2',2'-trifluoroethoxy)styryl)-[ 1,2,4]triazolo[ 3,4-α]phthalazine | 1268243-12-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: (E)-3-(4-(2',2',2'-trifluoroethoxy)styryl)-[ 1,2,4]triazolo[ 3,4-α]phthalazine
• 英文别名: 3-[(E)-2-[4-(2,2,2-trifluoroethoxy)phenyl]vinyl]-[1,2,4]triazolo[3,4-a]phthalazine；3-[(E)-2-[4-(2,2,2-trifluoroethoxy)phenyl]ethenyl]-[1,2,4]triazolo[3,4-a]phthalazine
• CAS: 1268243-12-4
• 化学式: C₁₉H₁₃F₃N₄O
• 分子量: 370.334
• InChiKey: HHYWSNVSJDBENN-JXMROGBWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  52.3
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  methyl 4-hydroxycinnamate 在 水 、 sodium hydride 、 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 作用下， 以 甲醇 、 二甲基亚砜 、 乙腈 、 mineral oil 为溶剂， 反应 51.5h， 生成 (E)-3-(4-(2',2',2'-trifluoroethoxy)styryl)-[ 1,2,4]triazolo[ 3,4-α]phthalazine
  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.