2-(2-(2-bromoethoxy)-5-chlorophenoxy)-3-chlorobenzonitrile | 1351861-77-2

• 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: 2-(2-(2-bromoethoxy)-5-chlorophenoxy)-3-chlorobenzonitrile
• 英文别名: 2-[2-(2-Bromoethoxy)-5-chlorophenoxy]-3-chlorobenzonitrile；2-[2-(2-bromoethoxy)-5-chlorophenoxy]-3-chlorobenzonitrile
• CAS: 1351861-77-2
• 化学式: C₁₅H₁₀BrCl₂NO₂
• 分子量: 387.06
• InChiKey: IMQPCCAGTPHOCX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  42.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(2-(2-bromoethoxy)-5-chlorophenoxy)-3-chlorobenzonitrile 、 2,4-二(三甲硅氧基)嘧啶 反应 1.5h， 以0.05 g的产率得到3-chloro-2-(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：

  3-氯-2-氟苯腈 在 偶氮二甲酸二异丙酯 、 三溴化硼 、 potassium carbonate 、 三苯基膦 作用下， 以 四氢呋喃 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 18.0h， 生成 2-(2-(2-bromoethoxy)-5-chlorophenoxy)-3-chlorobenzonitrile
  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

• [EN] CATECHOL DIETHERS AS POTENT ANTI-HIV AGENTS<br/>[FR] DIÉTHERS DE CATÉCHOL COMME AGENTS ANTI-HIV PUISSANTS
  申请人：UNIV YALE

  公开号：WO2013056003A2

  公开（公告）日：2013-04-18

  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.
• Computationally-Guided Optimization of a Docking Hit to Yield Catechol Diethers as Potent Anti-HIV Agents
  作者：Mariela Bollini、Robert A. Domaoal、Vinay V. Thakur、Ricardo Gallardo-Macias、Krasimir A. Spasov、Karen S. Anderson、William L. Jorgensen

  DOI：10.1021/jm201134m

  日期：2011.12.22

  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.