N-phenyl-2-{2-[4-(2-(phenylcarbamothioyl)hydrazinecarbonyl)phenylamino]benzoyl}hydrazinecarbothioamide | 1245567-57-0

• 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: N-phenyl-2-{2-[4-(2-(phenylcarbamothioyl)hydrazinecarbonyl)phenylamino]benzoyl}hydrazinecarbothioamide
• 英文别名: 1-Phenyl-3-[[2-[4-[(phenylcarbamothioylamino)carbamoyl]anilino]benzoyl]amino]thiourea
• CAS: 1245567-57-0
• 化学式: C₂₈H₂₅N₇O₂S₂
• 分子量: 555.684
• InChiKey: NSXQMOBYQPFHDH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  39
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  183
• 氢给体数：
  7
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-phenyl-2-{2-[4-(2-(phenylcarbamothioyl)hydrazinecarbonyl)phenylamino]benzoyl}hydrazinecarbothioamide 在 sodium hydroxide 作用下， 反应 3.0h， 以83%的产率得到4-phenyl-3-{2-[4-(4-phenyl-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)phenylamino]phenyl}-1H-1,2,4-triazole-5(4H)-thione
  参考文献：
  名称：

  Synthesis and biological evaluation of novel 2,4′-bis substituted diphenylamines as anticancer agents and potential epidermal growth factor receptor tyrosine kinase inhibitors

  摘要：

  Four new series of 2,4'-bis diphenylamine hydrazones 14, 2,4'-bis aminothiadiazole 16, 2,4'-bis mercaptotriazole 17-18 and 2,4'-bis mercapto-oxadiazole diphenylamine derivatives 19-20 were synthesized and evaluated for their ability to inhibit EGFR tyrosine kinase. Compound N-ethyl-5-{2-[4(5-(ethylamino)-1,3,4-thiadiazol-2-yl)- phenylaminolphenyl}-1,3,4-thiadiazol-2-amine 16a was the most active enzyme inhibitor (98% inhibition at 10 mu M). Moreover, all compounds that showed enzyme inhibition activity were tested in vitro on human breast carcinoma cell line (MCF-7) in which EGFR is highly expressed. The tested compounds exploited potent antitumor activity with IC50 values ranging 0.73-2.38 mu M. Molecular modeling and docking of the synthesized compounds into the active site of EGFR kinase domain showed good agreement with the obtained biological results. The present work represents a novel class of diphenylamine based derivatives with potent cytotoxicity and promising EGFR PTK inhibition activity. (C) 2010 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2010.05.072
• 作为产物：
  描述：

  2-[4-(hydrazinecarbonyl)phenylamino]benzoic acid hydrazide 、 硫代异氰酸苯酯 以 乙醇 为溶剂， 反应 8.0h， 以76%的产率得到N-phenyl-2-{2-[4-(2-(phenylcarbamothioyl)hydrazinecarbonyl)phenylamino]benzoyl}hydrazinecarbothioamide
  参考文献：
  名称：

  Synthesis and biological evaluation of novel 2,4′-bis substituted diphenylamines as anticancer agents and potential epidermal growth factor receptor tyrosine kinase inhibitors

  摘要：

  Four new series of 2,4'-bis diphenylamine hydrazones 14, 2,4'-bis aminothiadiazole 16, 2,4'-bis mercaptotriazole 17-18 and 2,4'-bis mercapto-oxadiazole diphenylamine derivatives 19-20 were synthesized and evaluated for their ability to inhibit EGFR tyrosine kinase. Compound N-ethyl-5-{2-[4(5-(ethylamino)-1,3,4-thiadiazol-2-yl)- phenylaminolphenyl}-1,3,4-thiadiazol-2-amine 16a was the most active enzyme inhibitor (98% inhibition at 10 mu M). Moreover, all compounds that showed enzyme inhibition activity were tested in vitro on human breast carcinoma cell line (MCF-7) in which EGFR is highly expressed. The tested compounds exploited potent antitumor activity with IC50 values ranging 0.73-2.38 mu M. Molecular modeling and docking of the synthesized compounds into the active site of EGFR kinase domain showed good agreement with the obtained biological results. The present work represents a novel class of diphenylamine based derivatives with potent cytotoxicity and promising EGFR PTK inhibition activity. (C) 2010 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2010.05.072

文献信息

• Novel Diphenylamine 2,4'-Dicarboxamide Based Azoles as Potential Epidermal Growth Factor Receptor Inhibitors: Synthesis and Biological Activity
  作者：Sahar Mahmoud Abou-Seri、Nahla Ahmed Farag、Ghaneya Sayed Hassan

  DOI：10.1248/cpb.59.1124

  日期：——

  Several hybrid molecules of diphenylamine-2,4′-dicarboxamide with various azolidinones and related heterocyclic rings have been synthesized and explored as epidermal growth factor receptor (EGFR) kinase inhibitors. Most of them displayed promising in vitro tyrosine kinase inhibition as well as potent cellular antiproliferative activity in the EGFR over-expressing breast cancer cell line (MCF-7). Compounds 12b and 13b that exhibited the highest inhibition in the kinase assay (89, 81% inhibition at 10 μM, respectively), showed potent antiproliferative effect against MCF-7 tumor cell line (IC50 1.04, 0.91 μM respectively). Molecular docking studies revealed that these compounds can bind to ATP binding site of the EGFR kinase domain and were involved in H-bonding with Met 793, in analogy to the known EGFR tyrosine kinase inhibitors. Moreover, compounds 15a—c possessed profound antitumor activity (IC50 0.59—0.73 μM) and significant EGFR-TK inhibition, making them of particular interest. In summary, the newly synthesized compounds provide promising new lead for the future design and development of anticancer agents of potential EGFR-TK inhibitory activity.

  作为表皮生长因子受体（EGFR）激酶抑制剂，人们合成并探索了几种二苯胺-2,4′-二甲酰胺与各种唑烷酮及相关杂环的杂化分子。其中大多数化合物都显示出良好的体外酪氨酸激酶抑制作用，并在表皮生长因子受体过度表达的乳腺癌细胞系（MCF-7）中显示出强大的细胞抗增殖活性。化合物 12b 和 13b 在激酶试验中表现出最高的抑制率（10 μM时的抑制率分别为 89% 和 81%），对 MCF-7 肿瘤细胞株也有很强的抗增殖作用（IC50 分别为 1.04 μM和 0.91 μM）。分子对接研究发现，这些化合物能与表皮生长因子受体激酶结构域的 ATP 结合位点结合，并与 Met 793 发生 H 键作用，这与已知的表皮生长因子受体酪氨酸激酶抑制剂类似。此外，化合物 15a-c 具有很强的抗肿瘤活性（IC50 0.59-0.73 μM）和显著的表皮生长因子受体-酪氨酸激酶抑制作用，因此特别令人感兴趣。总之，新合成的化合物为今后设计和开发具有潜在表皮生长因子受体-TK抑制活性的抗癌药物提供了新的线索。
• Synthesis and biological evaluation of novel 2,4′-bis substituted diphenylamines as anticancer agents and potential epidermal growth factor receptor tyrosine kinase inhibitors
  作者：Sahar Mahmoud Abou-Seri

  DOI：10.1016/j.ejmech.2010.05.072

  日期：2010.9

  Four new series of 2,4'-bis diphenylamine hydrazones 14, 2,4'-bis aminothiadiazole 16, 2,4'-bis mercaptotriazole 17-18 and 2,4'-bis mercapto-oxadiazole diphenylamine derivatives 19-20 were synthesized and evaluated for their ability to inhibit EGFR tyrosine kinase. Compound N-ethyl-5-2-[4(5-(ethylamino)-1,3,4-thiadiazol-2-yl)- phenylaminolphenyl}-1,3,4-thiadiazol-2-amine 16a was the most active enzyme inhibitor (98% inhibition at 10 mu M). Moreover, all compounds that showed enzyme inhibition activity were tested in vitro on human breast carcinoma cell line (MCF-7) in which EGFR is highly expressed. The tested compounds exploited potent antitumor activity with IC50 values ranging 0.73-2.38 mu M. Molecular modeling and docking of the synthesized compounds into the active site of EGFR kinase domain showed good agreement with the obtained biological results. The present work represents a novel class of diphenylamine based derivatives with potent cytotoxicity and promising EGFR PTK inhibition activity. (C) 2010 Elsevier Masson SAS. All rights reserved.