1,3-bis[4-chloro-2-(trifluoromethyl)phenyl]triazene | 931107-00-5

• 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: 1,3-bis[4-chloro-2-(trifluoromethyl)phenyl]triazene
• 英文别名: 4-chloro-N-[(E)-[4-chloro-2-(trifluoromethyl)phenyl]azo]-2-(trifluoromethyl)aniline；4-chloro-N-[[4-chloro-2-(trifluoromethyl)phenyl]diazenyl]-2-(trifluoromethyl)aniline
• CAS: 931107-00-5
• 化学式: C₁₄H₇Cl₂F₆N₃
• 分子量: 402.126
• InChiKey: PHXINARWTCRZKM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  36.8
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  [ruthenium(II)(η⁶-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]₂ 、 1,3-bis[4-chloro-2-(trifluoromethyl)phenyl]triazene 在 三乙胺 作用下， 以 甲醇 为溶剂， 反应 0.5h， 以78%的产率得到
  参考文献：
  名称：

  The 1,3-diaryltriazenido(p-cymene)ruthenium(II) complexes with a high in vitro anticancer activity

  摘要：

  1,3-Diatyltriazenes (1) were let to react with [RuCl2(p-cymene)](2) in the presence of trimethylamine to give neutral 1,3-diatyltriazenido(p-cymene)ruthenium(11) complexes, [RuCl(p-cymene)(ArNNNAr)] (2). The molecular composition of the products 2 was confirmed by NMR spectroscopy and mass spectrometry. The structures of the selected complexes were confirmed by a single crystal X-ray analysis. All triazenido-ruthenium complexes were highly cytotoxic against human cervical carcinoma HeLa cells with IC50 below 6 mu M, as determined by a spectrophotometric MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide) method. The most active was [RuCl(p-cymene)(ArNNNAr)] (Ar = 4-Cl-3-(CF3)-C6H3) (2g) with IC50 of 0.103 +/- 0.006 mu M. In comparison with the data for the non-coordinated triazenes 1, the triazenido-ruthenium complexes 2 exhibited up to 560-times higher activity. Three selected complexes were highly cytotoxic also against several tumor cell lines: laryngeal carcinoma HEp-2 cells and their drug-resistant HEp-2 subline (7 T), colorectal carcinoma HCT-116 cells, lung adenocarcinoma H460 cells, and mammary carcinoma MDA-MB-435 cells. The compounds 2g and [RuCl(p-cymene)(ArNNNAr)] (Ar = 4-I-C6H4) (2j) were similarly cytotoxic against parental and drug-resistant cells. Time and dose dependent accumulation of the cells in the S phase of the cell cycle was induced by the compound 2g, triggering apoptosis. Our preliminary results indicate triazenido-ruthenium complexes as promising anticancer drug candidates. (C) 2015 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.jinorgbio.2015.09.005
• 作为产物：
  描述：

  2-氨基-5-氯三氟甲苯 在 亚硝酸异戊酯 作用下， 以 苯 为溶剂， 反应 0.08h， 以75%的产率得到1,3-bis[4-chloro-2-(trifluoromethyl)phenyl]triazene
  参考文献：
  名称：

  新型强效抗肿瘤药4-硝基取代的1,3-二芳基三氮烯的合成与生物学评价

  摘要：

  我们描述了一种新型的1,3-二芳基三氮烯，即4-硝基取代的1,3-二芳基三氮烯的合成和生物活性。结构-活性关系分析表明，可以通过在苯环对位引入两个硝基和两个附加的吸电子基团（溴，氯，三氟甲基或氟）将1，3-二芳基三氮烯从无活性转变为具有高细胞毒性的化合物。取代基）在其邻位。为了增加改性化合物的溶解度，我们向其三氮烯氮中引入了各种酰基。LC-MS / MS分析的结果表明，N-酰基三氮烯可以被认为是非酰化的三氮烯的前药。选定的3-乙酰基1,3-双（2-氯-4-硝基苯基）-1-三氮烯（8b）对不同的肿瘤细胞系（包括顺铂耐药的喉癌细胞）具有高度的细胞毒性。值得注意的是，它对肿瘤细胞的抗增殖活性明显高于对正常细胞的抗增殖活性。DNA结合分析表明8b或其未酰化衍生物8a均未结合到DNA的小沟中。取而代之的是，8b会诱导活性氧，从而激发内质网（ER a）应激，最终导致细胞凋亡。我们的数据表明4-硝基取代

  DOI：

  10.1016/j.ejmech.2011.04.024

文献信息

• Anti-mycobacterial activity of 1,3-diaryltriazenes
  作者：Davie Cappoen、Jure Vajs、Cynthia Uythethofken、Andrej Virag、Vanessa Mathys、Marijan Kočevar、Luc Verschaeve、Martin Gazvoda、Slovenko Polanc、Kris Huygen、Janez Košmrlj

  DOI：10.1016/j.ejmech.2014.02.065

  日期：2014.4

  novel compounds for therapeutic use. Identification and study of compounds with the ability to inhibit Mycobacterium tuberculosis is of paramount importance. For this reason, a library of substituted 1,3-diaryltriazenes based on the acting component of the anti-trypanosomal drug, diminazene aceturate was created and evaluated for its potential as anti-tubercular agent. Several compounds were identified

  耐药性结核病的快速产生和传播导致对用于治疗用途的新型化合物的持续需求。鉴定和研究具有抑制结核分枝杆菌能力的化合物至关重要。因此，建立了基于抗锥虫药物地那米嗪乙酸酯的作用成分的取代的1,3-二芳基三氮烯文库，并对其作为抗结核药的潜力进行了评估。鉴定出对结核分枝杆菌和其他临床相关分枝杆菌物种（如牛分枝杆菌，鸟分枝杆菌和溃疡分枝杆菌）具有亚微摩尔抑制浓度的几种化合物。。尽管化合物的文库显示出相当大的急性细胞毒性，但未观察到遗传毒性。最后，选择具有最佳生物学特性的三氮烯14（IC 50  = 3.26μM，NI 50  = 24.22μM，SI  = 7.44）。化合物14显示出抑制细胞内复制和耐多药结核分枝杆菌生长的能力。结果表明该分子是进一步研究和优化的有趣支架。
• Diaryltriazenes as antibacterial agents against methicillin resistant Staphylococcus aureus (MRSA) and Mycobacterium smegmatis
  作者：Jure Vajs、Conor Proud、Anamaria Brozovic、Martin Gazvoda、Adrian Lloyd、David I. Roper、Maja Osmak、Janez Košmrlj、Christopher G. Dowson

  DOI：10.1016/j.ejmech.2016.12.060

  日期：2017.2

  Diaryltriazene derivatives were synthesized and evaluated for their antimicrobial properties. Initial experiments showed some of these compounds to have activity against both methicillin-resistant strains of Staphylococus aureus (MRSA) and Mycobacterium smegmatis, with MICs of 0.02 and 0.03 mu g/mL respectively. Those compounds with potent anti-staphylococcal and anti-mycobacterial activity were not found to act as growth inhibitors of mammalian cell lines or yeast. Furthermore, we demonstrated that one of the most active anti-MRSA diaryltriazene derivatives was subject to very low frequencies of resistance at <10(-9). Whole genome sequencing of resistant isolates identified mutations in the enzyme that lysylates phospholipids. This could result in the modification of phospholipid metabolism and consequently the characteristics of the staphylococcal cell membrane, ultimately modifying the sensitivity of these pathogens to triazene challenge. Our work has therefore extended the potential range of triazenes, which could yield novel antimicrobials with low levels of resistance. Crown Copyright (C) 2016 Published by Elsevier Masson SAS. All rights reserved.
• Synthesis and biological evaluation of 4-nitro-substituted 1,3-diaryltriazenes as a novel class of potent antitumor agents
  作者：Tamara Čimbora-Zovko、Anamaria Brozovic、Ivo Piantanida、Gerhard Fritz、Andrej Virag、Branko Alič、Vita Majce、Marijan Kočevar、Slovenko Polanc、Maja Osmak

  DOI：10.1016/j.ejmech.2011.04.024

  日期：2011.7

  We describe the synthesis and biological activity of a new class of 1,3-diaryltriazenes, namely 4-nitro-substituted 1,3-diaryltriazenes. Structure–activity relationship analysis reveals that 1,3-diaryltriazenes can be modified from inactive to highly cytotoxic compounds by the introduction of two nitro groups at the para positions of benzene rings and two additional electron-withdrawing groups (bromo

  我们描述了一种新型的1,3-二芳基三氮烯，即4-硝基取代的1,3-二芳基三氮烯的合成和生物活性。结构-活性关系分析表明，可以通过在苯环对位引入两个硝基和两个附加的吸电子基团（溴，氯，三氟甲基或氟）将1，3-二芳基三氮烯从无活性转变为具有高细胞毒性的化合物。取代基）在其邻位。为了增加改性化合物的溶解度，我们向其三氮烯氮中引入了各种酰基。LC-MS / MS分析的结果表明，N-酰基三氮烯可以被认为是非酰化的三氮烯的前药。选定的3-乙酰基1,3-双（2-氯-4-硝基苯基）-1-三氮烯（8b）对不同的肿瘤细胞系（包括顺铂耐药的喉癌细胞）具有高度的细胞毒性。值得注意的是，它对肿瘤细胞的抗增殖活性明显高于对正常细胞的抗增殖活性。DNA结合分析表明8b或其未酰化衍生物8a均未结合到DNA的小沟中。取而代之的是，8b会诱导活性氧，从而激发内质网（ER a）应激，最终导致细胞凋亡。我们的数据表明4-硝基取代
• The 1,3-diaryltriazenido(p-cymene)ruthenium(II) complexes with a high in vitro anticancer activity
  作者：Jure Vajs、Ivana Steiner、Anamaria Brozovic、Andrej Pevec、Andreja Ambriović-Ristov、Marija Matković、Ivo Piantanida、Damijana Urankar、Maja Osmak、Janez Košmrlj

  DOI：10.1016/j.jinorgbio.2015.09.005

  日期：2015.12

  1,3-Diatyltriazenes (1) were let to react with [RuCl2(p-cymene)](2) in the presence of trimethylamine to give neutral 1,3-diatyltriazenido(p-cymene)ruthenium(11) complexes, [RuCl(p-cymene)(ArNNNAr)] (2). The molecular composition of the products 2 was confirmed by NMR spectroscopy and mass spectrometry. The structures of the selected complexes were confirmed by a single crystal X-ray analysis. All triazenido-ruthenium complexes were highly cytotoxic against human cervical carcinoma HeLa cells with IC50 below 6 mu M, as determined by a spectrophotometric MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide) method. The most active was [RuCl(p-cymene)(ArNNNAr)] (Ar = 4-Cl-3-(CF3)-C6H3) (2g) with IC50 of 0.103 +/- 0.006 mu M. In comparison with the data for the non-coordinated triazenes 1, the triazenido-ruthenium complexes 2 exhibited up to 560-times higher activity. Three selected complexes were highly cytotoxic also against several tumor cell lines: laryngeal carcinoma HEp-2 cells and their drug-resistant HEp-2 subline (7 T), colorectal carcinoma HCT-116 cells, lung adenocarcinoma H460 cells, and mammary carcinoma MDA-MB-435 cells. The compounds 2g and [RuCl(p-cymene)(ArNNNAr)] (Ar = 4-I-C6H4) (2j) were similarly cytotoxic against parental and drug-resistant cells. Time and dose dependent accumulation of the cells in the S phase of the cell cycle was induced by the compound 2g, triggering apoptosis. Our preliminary results indicate triazenido-ruthenium complexes as promising anticancer drug candidates. (C) 2015 Elsevier Inc. All rights reserved.