4-(1-苯基三唑-4-基)苯胺 | 1232432-29-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 4-(1-苯基三唑-4-基)苯胺
• 英文名称: 4-(4-aminophenyl)-1-phenyl-1H-[1,2,3]triazole
• 英文别名: 4-(1-Phenyl-1H-1,2,3-triazol-4-yl)aniline；4-(1-phenyltriazol-4-yl)aniline
• CAS: 1232432-29-9
• 化学式: C₁₄H₁₂N₄
• 分子量: 236.276
• InChiKey: AYTGQSMEAHRXBK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  56.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(1-苯基三唑-4-基)苯胺 、 benzyl 7-chlorocarbonyl-2,2,3,3,4,4,5,5,6,6,7,7-dodecafluoroheptanoate 在 羟胺 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 5.0h， 生成 2,2,3,3,4,4,5,5,6,6,7,7-dodecafluorooctanedioic acid hydroxyamide (4-[1-phenyl-1H-[1,2,3]triazol-4-yl]phenyl)amide
  参考文献：
  名称：

  Synthesis and biochemical analysis of 2,2,3,3,4,4,5,5,6,6,7,7-dodecafluoro-N-hydroxy-octanediamides as inhibitors of human histone deacetylases

  摘要：

  Inhibition of human histone deacetylases (HDACs) has emerged as a novel concept in the chemotherapeutic treatment of cancer. Two chemical entities, SAHA (ZOLINZA, Merck) and romidepsin (Istodax, Celgene) have been recently approved by the FDA as first-in-class drugs against cutaneous T-cell lymphoma. Clinical use of these drugs revealed several side effects including gastro-intestinal symptoms, fatigue, thrombocytopenia, thrombosis. Romidepsin is associated with an yet unresolved cardiotoxicity issue. A general hypothesis for the diminishment of unwanted adverse effects and an improved therapeutical window suggests the development of more isotype selective inhibitors. In this study the first time HDAC inhibitors with perfluorinated spacers between the zinc chelating moiety and the aromatic capping group were synthesized and tested against representatives of HDAC classes I, IIa and IIb. Competitive binding assays and a combined approach by using blind docking and molecular dynamics support binding of the perfluorinated analogs of SAHA to the active site of the HDAC-like amidohydrolase from Bordetella/Alcaligenes and presumably also to human HDACs. In contrast to the alkyl spacer of SAHA and derivatives, the perfluorinated alkyl spacer seems to contribute to or facilitate the induction of selectivity for class 11, particularly class IIa, HDACs even though the overall potency of the perfluorinated SAHA analogs in this study against human HDACs remained still rather moderate in the micromolar range. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.11.041
• 作为产物：
  描述：

  对硝基肉桂酸 在 copper(ll) sulfate pentahydrate 、 palladium 10% on activated carbon 、 溴 、 一水合肼 、 溶剂黄146 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 、 维生素 C 作用下， 以 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.2h， 生成 4-(1-苯基三唑-4-基)苯胺
  参考文献：
  名称：

  设计，合成和生物学评估带有1、2、3-三唑部分的新型尿嘧啶衍生物作为胸苷酸合酶（TS）抑制剂和潜在的抗肿瘤药物

  摘要：

  胸苷酸合酶抑制剂的研究一直是抗癌药物开发的热点。在此，根据两种TS抑制剂的结构和药理特性，通过药物设计的分子组装原理，我们设计合成了30种新颖的尿嘧啶衍生物作为TS抑制剂。通过MTT分析评估了这些化合物对四种癌细胞系（A549，OVCAR-3，SGC-7901和HepG2）的抗增殖能力。它们中的大多数对所有测试的细胞系均表现出优异的活性。此外，hTS分析结果表明，这些化合物具有独特的体外抑制hTS活性的能力。值得注意的是，化合物13j对A549细胞表现出最强的活性（IC 50 = 1.18μM）和极显着的酶抑制（IC 50  = 0.13μM），优于培美曲塞（PTX，IC 50  = 3.29μM和IC 50  = 2.04μM）。流式细胞仪分析表明，化合物13j可以通过将细胞周期阻滞在G1 / S期来抑制A549细胞的增殖，进而诱导细胞凋亡。进一步的蛋白质印迹分析表明化合物13j可能下调周期检查点蛋白cyclin

  DOI：

  10.1016/j.ejmech.2019.03.047

文献信息

• [EN] HISTONE DEACETYLASE (HDAC) INHIBITING COMPOUNDS AND METHOD OF MAKING SAME<br/>[FR] COMPOSÉS INHIBANT L'HISTONE DÉSACÉTYLASE (HDAC) ET PROCÉDÉ DE FABRICATION DE CEUX-CI
  申请人：FELIX JAEGER UND DR STEFAN DRINKUTH LABORGEMEINSCHAFT OHG DR

  公开号：WO2012107304A1

  公开（公告）日：2012-08-16

  The invention relates to novel HDAC inhibitors and a method of making such HDAC inhibitors. The present invention provides novel HDAC inhibitors having a perfluorinated linker between the metal-binding group and the cap group.

  该发明涉及新型HDAC抑制剂及制备这种HDAC抑制剂的方法。本发明提供了具有全氟化连接剂的新型HDAC抑制剂，该连接剂位于金属结合基团和帽基团之间。
• Histone deacetylase (HDAC) inhibiting compounds and method of making same
  申请人：Dr. Felix Jäger und Dr. Stefan Drinkuth Laborgemeinschaft OHG

  公开号：EP2486923B1

  公开（公告）日：2015-09-09
• Design, synthesis and biological evaluation of novel uracil derivatives bearing 1, 2, 3-triazole moiety as thymidylate synthase (TS) inhibitors and as potential antitumor drugs
  作者：Guo-qing Lu、Xin-yang Li、Kamara Mohamed O、Depu Wang、Fan-hao Meng

  DOI：10.1016/j.ejmech.2019.03.047

  日期：2019.6

  Research on thymidylate synthase inhibitors has been a hot spot for anticancer drug development. Here, based on the structures and pharmacological properties of two types of TS inhibitors, through a molecular assembly principle of drugs design, we designed and synthesized a series of 30 novel uracil derivatives as TS inhibitors. The antiproliferative ability of these compounds was evaluated against

  胸苷酸合酶抑制剂的研究一直是抗癌药物开发的热点。在此，根据两种TS抑制剂的结构和药理特性，通过药物设计的分子组装原理，我们设计合成了30种新颖的尿嘧啶衍生物作为TS抑制剂。通过MTT分析评估了这些化合物对四种癌细胞系（A549，OVCAR-3，SGC-7901和HepG2）的抗增殖能力。它们中的大多数对所有测试的细胞系均表现出优异的活性。此外，hTS分析结果表明，这些化合物具有独特的体外抑制hTS活性的能力。值得注意的是，化合物13j对A549细胞表现出最强的活性（IC 50 = 1.18μM）和极显着的酶抑制（IC 50  = 0.13μM），优于培美曲塞（PTX，IC 50  = 3.29μM和IC 50  = 2.04μM）。流式细胞仪分析表明，化合物13j可以通过将细胞周期阻滞在G1 / S期来抑制A549细胞的增殖，进而诱导细胞凋亡。进一步的蛋白质印迹分析表明化合物13j可能下调周期检查点蛋白cyclin
• Synthesis and biochemical analysis of 2,2,3,3,4,4,5,5,6,6,7,7-dodecafluoro-N-hydroxy-octanediamides as inhibitors of human histone deacetylases
  作者：Leonhard M. Henkes、Patricia Haus、Felix Jäger、Joachim Ludwig、Franz-Josef Meyer-Almes

  DOI：10.1016/j.bmc.2011.11.041

  日期：2012.1

  Inhibition of human histone deacetylases (HDACs) has emerged as a novel concept in the chemotherapeutic treatment of cancer. Two chemical entities, SAHA (ZOLINZA, Merck) and romidepsin (Istodax, Celgene) have been recently approved by the FDA as first-in-class drugs against cutaneous T-cell lymphoma. Clinical use of these drugs revealed several side effects including gastro-intestinal symptoms, fatigue, thrombocytopenia, thrombosis. Romidepsin is associated with an yet unresolved cardiotoxicity issue. A general hypothesis for the diminishment of unwanted adverse effects and an improved therapeutical window suggests the development of more isotype selective inhibitors. In this study the first time HDAC inhibitors with perfluorinated spacers between the zinc chelating moiety and the aromatic capping group were synthesized and tested against representatives of HDAC classes I, IIa and IIb. Competitive binding assays and a combined approach by using blind docking and molecular dynamics support binding of the perfluorinated analogs of SAHA to the active site of the HDAC-like amidohydrolase from Bordetella/Alcaligenes and presumably also to human HDACs. In contrast to the alkyl spacer of SAHA and derivatives, the perfluorinated alkyl spacer seems to contribute to or facilitate the induction of selectivity for class 11, particularly class IIa, HDACs even though the overall potency of the perfluorinated SAHA analogs in this study against human HDACs remained still rather moderate in the micromolar range. (C) 2011 Elsevier Ltd. All rights reserved.