3-bromo-4,5-dimethoxy-benzaldehyde-thiosemicarbazone

• 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: 3-bromo-4,5-dimethoxy-benzaldehyde-thiosemicarbazone
• 英文别名: 3-Brom-4,5-dimethoxy-benzaldehyd-thiosemicarbazon；[(E)-(3-bromo-4,5-dimethoxyphenyl)methylideneamino]thiourea
• 化学式: C₁₀H₁₂BrN₃O₂S
• 分子量: 318.194
• InChiKey: CMWKKKFGGAVTLB-WLRTZDKTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  17
• 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 、 3-bromo-4,5-dimethoxy-benzaldehyde-thiosemicarbazone 在 sodium acetate 作用下， 以 乙醇 为溶剂， 反应 0.17h， 以69.3%的产率得到(E)-2-(2-(3-bromo-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：

  香草醛 在 溴 、 potassium carbonate 、 溶剂黄146 作用下， 以 甲醇 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 3-bromo-4,5-dimethoxy-benzaldehyde-thiosemicarbazone
  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

文献信息

• Thiosemicarbazones of Some Vanillin Derivatives
  作者：R. P. Perry

  DOI：10.1021/ja01642a073

  日期：1954.7
• Synthesis of 4-thiazolidinone analogs as potent in vitro anti-urease agents
  作者：Fazal Rahim、Khalid Zaman、Hayat Ullah、Muhammad Taha、Abdul Wadood、Muhammad Tariq Javed、Wajid Rehman、Muhammad Ashraf、Reaz Uddin、Imad Uddin、Humna Asghar、Aftab Ahmad Khan、Khalid M. Khan

  DOI：10.1016/j.bioorg.2015.10.005

  日期：2015.12

  4-Thiazolidinone analogs 1-20 were synthesized, characterized by H-1 NMR and EI-MS and investigated for urease inhibitory activity. All twenty (20) analogs exhibited varied degree of urease inhibitory potential with IC50 values 1.73-69.65 mu M, if compared with standard thiourea having IC50 value of 21.25 +/- 0.15 mu M. Among the series, eight derivatives 3, 6, 8, 10, 15, 17, 19, and 20 showed outstanding urease inhibitory potential with IC50 values of 9.34 +/- 0.02, 14.62 +/- 0.03, 8.43 +/- 0.01, 7.3 +/- 0.04, 2.31 +/- 0.002, 5.75 +/- 0.003, 8.81 +/- 0.005, and 1.73 +/- 0.001 mu M, respectively, which is better than the standard thiourea. The remaining analogs showed good to excellent urease inhibition. The binding interactions of these compounds were confirmed through molecular docking studies. (C) 2015 Elsevier Inc. All rights reserved.
• Winternitz; Mousseron, Travaux de la Societe de Pharmacie de Montpellier, 1950, vol. 10, p. 26
  作者：Winternitz、Mousseron

  DOI：——

  日期：——
• Design, synthesis and biological evaluation of bromophenol-thiazolylhydrazone hybrids inhibiting the interaction of translation initiation factors eIF4E/eIF4G as multifunctional agents for cancer treatment
  作者：Lijun Wang、Chuanlong Guo、Xiuxue Li、Xuemin Yu、Xiangqian Li、Kuo Xu、Bo Jiang、Xiaoling Jia、Chao Li、Dayong Shi

  DOI：10.1016/j.ejmech.2019.05.044

  日期：2019.9

  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.