(E)-2-(2,3-dibromo-4,5-dimethoxybenzylidene)hydrazine-1-carbothioamide

• 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: (E)-2-(2,3-dibromo-4,5-dimethoxybenzylidene)hydrazine-1-carbothioamide
• 英文别名: 2-(2,3-dibromo-4,5-dimethoxybenzylidene)hydrazine-1-carbothioamide；[(E)-(2,3-dibromo-4,5-dimethoxyphenyl)methylideneamino]thiourea
• 化学式: C₁₀H₁₁Br₂N₃O₂S
• 分子量: 397.09
• InChiKey: AEEVFFOEEWVLGF-LNKIKWGQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-溴-4'-(三氟甲基)苯乙酮 、 (E)-2-(2,3-dibromo-4,5-dimethoxybenzylidene)hydrazine-1-carbothioamide 在 sodium acetate 作用下， 以 乙醇 为溶剂， 反应 0.17h， 以66.3%的产率得到(E)-2-(2-(2,3-dibromo-4,5-dimethoxybenzylidene)hydrazinyl)-4 -(4-(trifluoromethyl)phenyl)thiazole
  参考文献：
  名称：

  Design, synthesis and biological evaluation of bromophenol-thiazolylhydrazone hybrids inhibiting the interaction of translation initiation factors eIF4E/eIF4G as multifunctional agents for cancer treatment

  摘要：

  The eukaryotic initiation factor 4E (eIF4E) is an emerging anticancer drug target for specific anticancer therapy as a promising approach to overcome drug resistance and promote chemotherapy antitumor efficacy. A series of bromophenol-thiazotylhydrazone hybrids were designed, synthesized and evaluated for their antitumor activities. Among of them, the most potent compound 3e (EGPI-1) could inhibit the eIF4E/eIF4G interaction. Further mechanism study demonstrated EGPI-1 played an antitumor role in multiple modes of action including regulating the activity of elF4E by inhibiting the phosphorylation of eIF4E and 4EBPI, disrupting mitochondrial function through the mTOR/4EBP1 signaling pathway, and inducing autophagy, apoptosis and ROS generation. Moreover, EGPI-1 showed good safety and favorable pharmacokinetic properties in vivo. These observations demonstrate that EGPI-1 may serve as an excellent lead compound for the development of new anticancer drugs that target the eIF4E/eIF4G interface and as a chemical genetic probe to investigate the role of the eIF4E in biological processes and human diseases. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.05.044
• 作为产物：
  描述：

  3-溴-4,5-二甲氧基苯甲醛 在 溴 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 生成 (E)-2-(2,3-dibromo-4,5-dimethoxybenzylidene)hydrazine-1-carbothioamide
  参考文献：
  名称：

  Design, synthesis and biological evaluation of bromophenol-thiazolylhydrazone hybrids inhibiting the interaction of translation initiation factors eIF4E/eIF4G as multifunctional agents for cancer treatment

  摘要：

  The eukaryotic initiation factor 4E (eIF4E) is an emerging anticancer drug target for specific anticancer therapy as a promising approach to overcome drug resistance and promote chemotherapy antitumor efficacy. A series of bromophenol-thiazotylhydrazone hybrids were designed, synthesized and evaluated for their antitumor activities. Among of them, the most potent compound 3e (EGPI-1) could inhibit the eIF4E/eIF4G interaction. Further mechanism study demonstrated EGPI-1 played an antitumor role in multiple modes of action including regulating the activity of elF4E by inhibiting the phosphorylation of eIF4E and 4EBPI, disrupting mitochondrial function through the mTOR/4EBP1 signaling pathway, and inducing autophagy, apoptosis and ROS generation. Moreover, EGPI-1 showed good safety and favorable pharmacokinetic properties in vivo. These observations demonstrate that EGPI-1 may serve as an excellent lead compound for the development of new anticancer drugs that target the eIF4E/eIF4G interface and as a chemical genetic probe to investigate the role of the eIF4E in biological processes and human diseases. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.05.044