(E)-3-[4-(benzyloxy)-3-bromo-5-methoxyphenyl]acrylonitrile

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (E)-3-[4-(benzyloxy)-3-bromo-5-methoxyphenyl]acrylonitrile
• 英文别名: (E)-3-(3-bromo-5-methoxy-4-phenylmethoxyphenyl)prop-2-enenitrile
• 化学式: C₁₇H₁₄BrNO₂
• 分子量: 344.208
• InChiKey: FXWKOVPOWPEQJB-VMPITWQZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 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：

  (E)-3-[4-(benzyloxy)-3-bromo-5-methoxyphenyl]acrylonitrile 在 palladium 10% on activated carbon 、 氢气 、 zinc(II) chloride 作用下， 以 乙酸乙酯 为溶剂， 反应 1.5h， 以74%的产率得到2-bromo-4-(2-cyanoethyl)-6-methoxyphenol
  参考文献：
  名称：

  Novel HIV-1 Non-nucleoside Reverse Transcriptase Inhibitor Agents: Optimization of Diarylanilines with High Potency against Wild-Type and Rilpivirine-Resistant E138K Mutant Virus

  摘要：

  Three series (6, 13, and 14) of new diarylaniline (DAAN) analogues were designed, synthesized, and evaluated for anti-HIV potency, especially against the E138K viral strain with a major mutation conferring resistance to the new generation non-nucleoside reverse transcriptase inhibitor drug rilpivirine (1b). Promising new compounds were then assessed for physicochemical and associated pharmaceutical properties, including aqueous solubility, log P value, and metabolic stability, as well as predicted lipophilic parameters of ligand efficiency, ligand lipophilic efficiency, and ligand efficiency-dependent lipophilicity indices, which are associated with ADME property profiles. Compounds 6a, 14c, and 14d showed high potency against the 1b-resistant E138K mutated viral strain as well as good balance between anti-HIV-1 activity and desirable druglike properties. From the perspective of optimizing future NNRTI compounds as clinical trial candidates, computational modeling results provided valuable information about how the R-1 group might provide greater efficacy against the E138K mutant.

  DOI：

  10.1021/acs.jmedchem.5b01827
• 作为产物：
  描述：

  氰甲基磷酸二乙酯 、 4-苄氧基-3-溴-5-甲氧基苯甲醛 在 potassium tert-butylate 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以1.3 g的产率得到(E)-3-[4-(benzyloxy)-3-bromo-5-methoxyphenyl]acrylonitrile
  参考文献：
  名称：

  Novel HIV-1 Non-nucleoside Reverse Transcriptase Inhibitor Agents: Optimization of Diarylanilines with High Potency against Wild-Type and Rilpivirine-Resistant E138K Mutant Virus

  摘要：

  Three series (6, 13, and 14) of new diarylaniline (DAAN) analogues were designed, synthesized, and evaluated for anti-HIV potency, especially against the E138K viral strain with a major mutation conferring resistance to the new generation non-nucleoside reverse transcriptase inhibitor drug rilpivirine (1b). Promising new compounds were then assessed for physicochemical and associated pharmaceutical properties, including aqueous solubility, log P value, and metabolic stability, as well as predicted lipophilic parameters of ligand efficiency, ligand lipophilic efficiency, and ligand efficiency-dependent lipophilicity indices, which are associated with ADME property profiles. Compounds 6a, 14c, and 14d showed high potency against the 1b-resistant E138K mutated viral strain as well as good balance between anti-HIV-1 activity and desirable druglike properties. From the perspective of optimizing future NNRTI compounds as clinical trial candidates, computational modeling results provided valuable information about how the R-1 group might provide greater efficacy against the E138K mutant.

  DOI：

  10.1021/acs.jmedchem.5b01827

文献信息

• Novel HIV-1 Non-nucleoside Reverse Transcriptase Inhibitor Agents: Optimization of Diarylanilines with High Potency against Wild-Type and Rilpivirine-Resistant E138K Mutant Virus
  作者：Na Liu、Lei Wei、Li Huang、Fei Yu、Weifan Zheng、Bingjie Qin、Dong-Qin Zhu、Susan L. Morris-Natschke、Shibo Jiang、Chin-Ho Chen、Kuo-Hsiung Lee、Lan Xie

  DOI：10.1021/acs.jmedchem.5b01827

  日期：2016.4.28

  Three series (6, 13, and 14) of new diarylaniline (DAAN) analogues were designed, synthesized, and evaluated for anti-HIV potency, especially against the E138K viral strain with a major mutation conferring resistance to the new generation non-nucleoside reverse transcriptase inhibitor drug rilpivirine (1b). Promising new compounds were then assessed for physicochemical and associated pharmaceutical properties, including aqueous solubility, log P value, and metabolic stability, as well as predicted lipophilic parameters of ligand efficiency, ligand lipophilic efficiency, and ligand efficiency-dependent lipophilicity indices, which are associated with ADME property profiles. Compounds 6a, 14c, and 14d showed high potency against the 1b-resistant E138K mutated viral strain as well as good balance between anti-HIV-1 activity and desirable druglike properties. From the perspective of optimizing future NNRTI compounds as clinical trial candidates, computational modeling results provided valuable information about how the R-1 group might provide greater efficacy against the E138K mutant.