3-氯-5-(5-氯-2-羟基苯氧基)苯甲腈 | 895572-24-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 3-氯-5-(5-氯-2-羟基苯氧基)苯甲腈
• 英文名称: 3-chloro-5-(5-chloro-2-hydroxyphenoxy)benzonitrile
• CAS: 895572-24-4
• 化学式: C₁₃H₇Cl₂NO₂
• 分子量: 280.11
• InChiKey: LMSOLKXHBMKBFV-UHFFFAOYSA-N

物化性质

• 沸点：
  376.5±42.0 °C(Predicted)
• 密度：
  1.50±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  53.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-氯-5-(5-氯-2-羟基苯氧基)苯甲腈 在 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 反应 1.5h， 生成 3-chloro-5-(5-chloro-2-(2-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)ethoxy)phenoxy)benzonitrile
  参考文献：
  名称：

  Computationally-Guided Optimization of a Docking Hit to Yield Catechol Diethers as Potent Anti-HIV Agents

  摘要：

  A 5-mu M docking hit has been optimized to an extraordinarily potent (55 pM) non-nucleoside inhibitor of HIV reverse transcriptase. Use of free energy perturbation (PEP) calculations to predict relative free energies of binding aided the optimizations by identifying optimal substitution patterns for phenyl rings and a linker. The most potent resultant catechol diethers feature terminal uracil and cyanovinylphenyl groups. A halogen bond with Pro95 likely contributes to the extreme potency of compound 42. In addition, several examples are provided illustrating failures of attempted grafting of a substructure from a very active compound onto a seemingly related scaffold to improve its activity.

  DOI：

  10.1021/jm201134m
• 作为产物：
  描述：

  5-氯-2-甲氧基-苯酚 在 三溴化硼 、 potassium carbonate 作用下， 以 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 18.0h， 生成 3-氯-5-(5-氯-2-羟基苯氧基)苯甲腈
  参考文献：
  名称：

  Computationally-Guided Optimization of a Docking Hit to Yield Catechol Diethers as Potent Anti-HIV Agents

  摘要：

  A 5-mu M docking hit has been optimized to an extraordinarily potent (55 pM) non-nucleoside inhibitor of HIV reverse transcriptase. Use of free energy perturbation (PEP) calculations to predict relative free energies of binding aided the optimizations by identifying optimal substitution patterns for phenyl rings and a linker. The most potent resultant catechol diethers feature terminal uracil and cyanovinylphenyl groups. A halogen bond with Pro95 likely contributes to the extreme potency of compound 42. In addition, several examples are provided illustrating failures of attempted grafting of a substructure from a very active compound onto a seemingly related scaffold to improve its activity.

  DOI：

  10.1021/jm201134m

文献信息

• Non-nucleoside reverse transcriptase inhibitors
  申请人：Sweeney Zachary Kevin

  公开号：US20080249151A1

  公开（公告）日：2008-10-09

  Compounds of formula I, wherein R 1 , R 2 , R 3 , R 4 , R 5 , X, Y, and Ar are as defined herein or pharmaceutically acceptable salts thereof, inhibit HIV-1 reverse transcriptase and afford a method for prevention and treatment of HIV-1 infections and the treatment of AIDS and/or ARC. The present invention also relates to compositions containing compounds of formula I useful for the prevention and treatment of HIV-1 infections and the treatment of AIDS and/or ARC.

  式I的化合物，其中R1、R2、R3、R4、R5、X、Y和Ar如本文所定义或其药学上可接受的盐，抑制HIV-1逆转录酶，并提供一种预防和治疗HIV-1感染以及治疗艾滋病和/或ARC的方法。本发明还涉及含有式I化合物的组合物，用于预防和治疗HIV-1感染以及治疗艾滋病和/或ARC。
• Diaryl ethers with carboxymethoxyphenacyl motif as potent HIV-1 reverse transcriptase inhibitors with improved solubility
  作者：Tomasz Frączek、Rafał Kamiński、Agnieszka Krakowiak、Evelien Naessens、Bruno Verhasselt、Piotr Paneth

  DOI：10.1080/14756366.2017.1387542

  日期：2018.1.1

  In search of new non-nucleoside reverse transcriptase inhibitors (NNRTIs) with improved solubility, two series of novel diaryl ethers with phenacyl moiety were designed and evaluated for their HIV-1 reverse transcriptase inhibition potentials. All compounds exhibited good to excellent results with IC50 at low micromolar to submicromolar concentrations. Two most active compounds (7e and 7 g) exhibit

  为了寻找具有改善的溶解度的新的非核苷逆转录酶抑制剂（NNRTIs），设计了两个具有苯甲酰基部分的新型二芳基醚，并评估了其对HIV-1逆转录酶抑制的潜力。在低微摩尔至亚微摩尔浓度下，所有化合物的IC50均显示出良好至优异的结果。两种活性最高的化合物（7e和7 g）显示出的抑制效力与奈韦拉平和利比韦林相当，甚至更好。此外，最有前途的（7e）的SupT1和CD4 +细胞感染性试验已证实其强大的抗病毒潜力，而对接研究表明，新型的结合相互作用可导致高活性。
• CATECHOL DIETHERS AS POTENT ANTI-HIV AGENTS
  申请人：YALE UNIVERSITY

  公开号：US20140288017A1

  公开（公告）日：2014-09-25

  The present invention is directed to novel catechol diether compounds, pharmaceutical compositions therefrom and methods for inhibiting reverse transcriptase and treating HIV infections, especially included drug resistant strains of HIV 1 and 2 and/or secondary disease states and/or conditions which occur as a consequence of HIV infection.

  本发明涉及新型儿茶酚二醚化合物、其制药组合物以及抑制反转录酶和治疗HIV感染的方法，特别包括抗药性HIV 1和2以及/或作为HIV感染后果的二级疾病状态和/或条件。
• WO2006/67587
  申请人：——

  公开号：——

  公开（公告）日：——
• NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS
  申请人：F. Hoffmann-La Roche AG

  公开号：EP2142520A1

  公开（公告）日：2010-01-13