3-{4'-[(4-chloro-3-trifluoromethylphenyl)guanidino]phenylamino}phenylguanidine dihydrochloride

• 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-{4'-[(4-chloro-3-trifluoromethylphenyl)guanidino]phenylamino}phenylguanidine dihydrochloride
• 英文别名: 1-[4-Chloro-3-(trifluoromethyl)phenyl]-2-[4-[3-(diaminomethylideneamino)anilino]phenyl]guanidine;hydrochloride；1-[4-chloro-3-(trifluoromethyl)phenyl]-2-[4-[3-(diaminomethylideneamino)anilino]phenyl]guanidine;hydrochloride
• 化学式: C₂₁H₁₉ClF₃N₇*2ClH
• 分子量: 534.799
• InChiKey: MATBQXDQQCLDGG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.49
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  127
• 氢给体数：
  6
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3-硝基氯苯 在 盐酸 、 potassium phosphate 、 tris-(dibenzylideneacetone)dipalladium(0) 、 palladium 10% on activated carbon 、 氢气 、 三乙胺 、 mercury dichloride 、 2-(二环己基膦基)联苯 作用下， 以 1,4-二氧六环 、 乙二醇二甲醚 、 乙醇 、 二氯甲烷 、 乙酸乙酯 、 异丙醇 为溶剂， 100.0 ℃ 、303.99 kPa 条件下， 反应 41.0h， 生成 3-{4'-[(4-chloro-3-trifluoromethylphenyl)guanidino]phenylamino}phenylguanidine dihydrochloride
  参考文献：
  名称：

  Guanidinium-based derivatives: Searching for new kinase inhibitors

  摘要：

  Considering the structural similarities between the kinase inhibitor sorafenib and 4,4'-bis-guanidinium derivatives previously prepared by Rozas and co., which display interesting cytotoxicity in cancer cells, we have studied whether this activity could result from kinase inhibition. Five new families have been prepared consisting of unsubstituted and aryl-substituted 3,4'-bis-guanidiniums, 3,4'-bis-2-aminoimidazolinium and 3-acetamide-4'-(4-chloro-3-trifluoromethylphenyl)guanidinium derivatives. Cytotoxicity (measuring the IC50 values) and apoptosis studies in human HL-60 promyelocytic leukemia cells were carried out for these compounds. Additionally, their potential inhibitory effect was explored on a panel of kinases known to be involved in apoptotic pathways. The previously prepared cytotoxic 4,4'-bis-guanidiniums did not inhibit any of these kinases; however, some of the novel 3,4'-substituted derivatives showed a high percentage inhibition of RAF-1/MEK-1, for which the potential mode of binding was evaluated by docking studies. The interesting antitumour properties showed by these compounds open up new exciting lines of investigation for kinase inhibitors as anticancer agents and also highlights the relevance of the guanidinium moiety for protein kinase inhibitors chemical design. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.05.025

文献信息

• Guanidinium-based derivatives: Searching for new kinase inhibitors
  作者：Elena Diez-Cecilia、Brendan Kelly、Concepcion Perez、Daniela M. Zisterer、Daniel K. Nevin、David G. Lloyd、Isabel Rozas

  DOI：10.1016/j.ejmech.2014.05.025

  日期：2014.6

  Considering the structural similarities between the kinase inhibitor sorafenib and 4,4'-bis-guanidinium derivatives previously prepared by Rozas and co., which display interesting cytotoxicity in cancer cells, we have studied whether this activity could result from kinase inhibition. Five new families have been prepared consisting of unsubstituted and aryl-substituted 3,4'-bis-guanidiniums, 3,4'-bis-2-aminoimidazolinium and 3-acetamide-4'-(4-chloro-3-trifluoromethylphenyl)guanidinium derivatives. Cytotoxicity (measuring the IC50 values) and apoptosis studies in human HL-60 promyelocytic leukemia cells were carried out for these compounds. Additionally, their potential inhibitory effect was explored on a panel of kinases known to be involved in apoptotic pathways. The previously prepared cytotoxic 4,4'-bis-guanidiniums did not inhibit any of these kinases; however, some of the novel 3,4'-substituted derivatives showed a high percentage inhibition of RAF-1/MEK-1, for which the potential mode of binding was evaluated by docking studies. The interesting antitumour properties showed by these compounds open up new exciting lines of investigation for kinase inhibitors as anticancer agents and also highlights the relevance of the guanidinium moiety for protein kinase inhibitors chemical design. (C) 2014 Elsevier Masson SAS. All rights reserved.