4-((4-chloro-6-(mesityloxy)-1,3,5-triazin-2-yl)amino)benzonitrile

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-((4-chloro-6-(mesityloxy)-1,3,5-triazin-2-yl)amino)benzonitrile
• 英文别名: 4-[[4-Chloro-6-(2,4,6-trimethylphenoxy)-1,3,5-triazin-2-yl]amino]benzonitrile；4-[[4-chloro-6-(2,4,6-trimethylphenoxy)-1,3,5-triazin-2-yl]amino]benzonitrile
• 化学式: C₁₉H₁₆ClN₅O
• 分子量: 365.822
• InChiKey: WPKDUEYVHLCIHE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  83.7
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-((4-chloro-6-(mesityloxy)-1,3,5-triazin-2-yl)amino)benzonitrile 在 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 为溶剂， 反应 96.0h， 生成 4-((4-((2-((4-((4-cyanophenyl)amino)-6-(mesitylamino)-1,3,5-triazin-2-yl)amino)ethyl)amino)-6-(mesityloxy)-1,3,5-triazin-2-yl)amino)benzonitrile
  参考文献：
  名称：

  新型三嗪二聚体具有强大的抗锥虫活性

  摘要：

  人类非洲锥虫病（HAT），也称为昏睡病是一种由“ Glossina”昆虫叮咬传播的寄生虫病，通常被称为“采采蝇”。这种疾病主要影响生活在非洲偏远农村地区的贫困人口。未经处理，通常会致命。当前，缺乏针对该疾病的安全有效的治疗方法。对三嗪非核苷HIV-1逆转录酶抑制剂（单体）的表型筛选产生了有效的和选择性的抗锥虫类化合物。这种偶然发现和在对这些被忽视的热带病有活性的许多化合物中都存在二聚体，促使我们研究三嗪二聚体的抗锥虫活性。最优化的三嗪二聚体产生了3,3'-（（（乙烷-1,2-二基双（氮杂二氮基））双（4-（甲磺酰氧基）-1,3,5-三嗪-6，），这种化合物在体外具有非常强的效力，在体内具有中等的抗锥虫活性。

  DOI：

  10.1016/j.ejmech.2017.11.075
• 作为产物：
  描述：

  3,4,5-三甲基苯酚 在 potassium carbonate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 生成 4-((4-chloro-6-(mesityloxy)-1,3,5-triazin-2-yl)amino)benzonitrile
  参考文献：
  名称：

  Design, Synthesis, and Anti-HIV Evaluation of Novel Triazine Derivatives Targeting the Entrance Channel of the NNRTI Binding Pocket

  摘要：

  A novel series of triazine derivatives targeting the entrance channel of the HIV‐1 non‐nucleoside reverse transcriptase inhibitor binding pocket (NNIBP) were designed and synthesized on the basis of our previous work. The results of a cell‐based antiviral screening assay indicated that most compounds showed good‐to‐moderate activity against wild‐type HIV‐1 with EC50 values within the concentration range of 0.0078–0.16 μm (compound DCS‐a4, EC50 = 7.8 nm). Some compounds displayed submicromolar activity against the K103N/Y181C resistant mutant strain (such as compound DCS‐a4, EC50 = 0.65 μm). Molecular modeling studies confirmed that the new compounds could bind into the NNIBP similarly as the lead compound, and the newly introduced flexible heterocycles could occupy the entrance channel effectively. In addition, the preliminary structure–activity relationship and the RT inhibitory assay are presented in this study.

  DOI：

  10.1111/cbdd.12471

文献信息

• [EN] TRIAZINES WITH SUITABLE SPACERS FOR TREATMENT AND/OR PREVENTION OF HIV INFECTIONS<br/>[FR] TRIAZINES COMPRENANT DES ESPACEURS APPROPRIÉS POUR LE TRAITEMENT ET/OU LA PRÉVENTION D'INFECTIONS PAR LE VIH
  申请人：UNIV ANTWERPEN

  公开号：WO2013139727A1

  公开（公告）日：2013-09-26

  The present invention relates to the field of HIV-1 infections, and in particular provides novel compounds containing triazine rings and suitable spacers. The compounds according to this invention are very suitable for the prevention and/or treatment of HIV-1 infection and in particular show improved activity against NNRTI-resistant viruses of HIV-1.

  本发明涉及HIV-1感染领域，特别提供了含有三嗪环和适当间隔物的新型化合物。根据本发明的化合物非常适用于预防和/或治疗HIV-1感染，特别显示出对HIV-1的NNRTI耐药病毒具有改进的活性。
• [EN] DISUBSTITUTED TRIAZINE DIMERS FOR TREATMENT AND/OR PREVENTION OF INFECTIOUS DISEASES<br/>[FR] DIMÈRES DE TRIAZINE DISUBSTITUÉE POUR LE TRAITEMENT E/OU LA PRÉVENTION DE MALADIES INFECTIEUSES
  申请人：UNIV ANTWERPEN

  公开号：WO2013068551A1

  公开（公告）日：2013-05-16

  The present invention relates to novel compounds (I) containing two disubstituted triazine rings covalently linked by an organic linker, thereby creating dimers. These compounds show activity against the causative infective agents of infectious diseases such as African trypanosomiasis, Chagas disease, Leishmaniasis, Malaria and HIV. The invention further relates to the prevention and/or treatment of these diseases.

  本发明涉及一种新型化合物（I），其中包含通过有机连接剂共价连接的两个二取代三嗪环，从而形成二聚体。这些化合物对致病的传染病如非洲锥虫病、克氏病、利什曼病、疟疾和艾滋病的感染性病原体表现出活性。该发明还涉及预防和/或治疗这些疾病。
• Synthesis, evaluation and structure–activity relationships of triazine dimers as novel antiviral agents
  作者：Muthusamy Venkatraj、Kevin K. Ariën、Jan Heeres、Jurgen Joossens、Jonas Messagie、Johan Michiels、Pieter Van der Veken、Guido Vanham、Paul J. Lewi、Koen Augustyns

  DOI：10.1016/j.bmcl.2012.09.066

  日期：2012.12

  This letter reports the synthesis and structure–activity relationship (SAR) study of a series of triazine dimers as novel antiviral agents. These compounds were obtained through a bivalent ligand approach in which two triazine moieties are covalently connected by suitable linkers. Several compounds showed submicromolar activity against wild-type HIV-1 and moderate activity against single mutant strains

  这封信报道了一系列三嗪二聚体作为新型抗病毒药物的合成和结构-活性关系（SAR）研究。这些化合物是通过二价配体方法获得的，其中两个三嗪部分通过合适的接头共价连接。几种化合物对野生型HIV-1表现出亚微摩尔活性，对单个突变株具有中等活性。
• DISUBSTITUTED TRIAZINE DIMERS FOR TREATMENT AND/OR PREVENTION OF INFECTIOUS DISEASES
  申请人：LEWI Wim

  公开号：US20140323488A1

  公开（公告）日：2014-10-30

  The present invention relates to novel compounds (I) containing two disubstituted triazine rings covalently linked by an organic linker, thereby creating dimers. These compounds show activity against the causative infective agents of infectious diseases such as African trypanosomiasis, Chagas disease, Leishmaniasis, Malaria and HIV. The invention further relates to the prevention and/or treatment of these diseases.

  本发明涉及包含两个二取代三嗪环的新化合物（I），通过有机连接物共价连接，从而形成二聚体。这些化合物对引起传染病如非洲锥虫病、克氏病、利什曼病、疟疾和艾滋病的致病性感染剂表现出活性。该发明还涉及这些疾病的预防和/或治疗。
• Evolution of Anti-HIV Drug CandidatesPart 2: Diaryltriazine (DATA) Analogues
  作者：Donald W. Ludovici、Robert W. Kavash、Michael J. Kukla、Chih Y. Ho、Hong Ye、Bart L. De Corte、Koen Andries、Marie-Pierre de Béthune、Hilde Azijn、Rudi Pauwels、Henry E.L. Moereels、Jan Heeres、Lucien M.H. Koymans、Marc R. de Jonge、Koen J.A. Van Aken、Frederik F.D. Daeyaert、Paul J. Lewi、Kalyan Das、Edward Arnold、Paul A.J. Janssen

  DOI：10.1016/s0960-894x(01)00411-5

  日期：2001.9

  A synthesis program directed toward improving the stability of imidoyl thiourea based non-nucleoside reverse transcriptase inhibitors (NNRTIs) led to the discovery of diaryltriazines (DATAs), a new class of potent NNRTIs. The synthesis and anti-HIV structure-activity relationship (SAR) studies of a series of DATA derivatives are described. (C) 2001 Elsevier Science Ltd. All rights reserved.