5-fluoro-2-[(6-oxo-7-{[2-(trimethylsilyl)ethoxy]methoxy}-6,7,8,9-tetrahydro-3H-pyrrolo[2,3-c][1,7]naphthyridin-3-yl)methyl]benzonitrile | 1293388-04-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 5-fluoro-2-[(6-oxo-7-{[2-(trimethylsilyl)ethoxy]methoxy}-6,7,8,9-tetrahydro-3H-pyrrolo[2,3-c][1,7]naphthyridin-3-yl)methyl]benzonitrile
• 英文别名: 5-Fluoro-2-[[6-oxo-7-(2-trimethylsilylethoxymethoxy)-8,9-dihydropyrrolo[2,3-c][1,7]naphthyridin-3-yl]methyl]benzonitrile
• CAS: 1293388-04-1
• 化学式: C₂₄H₂₇FN₄O₃Si
• 分子量: 466.587
• InChiKey: HSKATHYDKYDJEI-UHFFFAOYSA-N

物化性质

• 沸点：
  659.0±55.0 °C(Predicted)
• 密度：
  1.23±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.34
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  80.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-fluoro-2-[(6-oxo-7-{[2-(trimethylsilyl)ethoxy]methoxy}-6,7,8,9-tetrahydro-3H-pyrrolo[2,3-c][1,7]naphthyridin-3-yl)methyl]benzonitrile 在 硫酸 、 水 、 碳酸氢钠 作用下， 以 异丙醇 、 二氯甲烷 为溶剂， 反应 22.0h， 以88%的产率得到5-fluoro-2-[(7-hydroxy-6-oxo-6,7,8,9-tetrahydro-3H-pyrrolo[2,3-c][1,7]naphthyridin-3-yl)methyl]benzonitrile
  参考文献：
  名称：

  Design and Synthesis of Novel N-Hydroxy-Dihydronaphthyridinones as Potent and Orally Bioavailable HIV-1 Integrase Inhibitors

  摘要：

  HIV-1 integrase (IN) is one of three enzymes encoded by the HIV genome and is essential for viral replication, and HIV-1 IN inhibitors have emerged as a new promising class of therapeutics. Recently, we reported the synthesis of orally bioavailable azaindole hydroxamic acids that were potent inhibitors of the HIV-1 IN enzyme. Here we disclose the design and synthesis of novel tricyclic N-hydroxy-dihydronaphthyridinones as potent, orally bioavailable HIV-1 integrase inhibitors displaying excellent ligand and lipophilic efficiencies.

  DOI：

  10.1021/jm200208d
• 作为产物：
  描述：

  O-((2-trimethylsilylethoxy)methyl)hydroxylamine 在 sodium hydride 、 sodium cyanoborohydride 、 对甲苯磺酸 、 溶剂黄146 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 mineral oil 为溶剂， 反应 9.0h， 生成 5-fluoro-2-[(6-oxo-7-{[2-(trimethylsilyl)ethoxy]methoxy}-6,7,8,9-tetrahydro-3H-pyrrolo[2,3-c][1,7]naphthyridin-3-yl)methyl]benzonitrile
  参考文献：
  名称：

  Design and Synthesis of Novel N-Hydroxy-Dihydronaphthyridinones as Potent and Orally Bioavailable HIV-1 Integrase Inhibitors

  摘要：

  HIV-1 integrase (IN) is one of three enzymes encoded by the HIV genome and is essential for viral replication, and HIV-1 IN inhibitors have emerged as a new promising class of therapeutics. Recently, we reported the synthesis of orally bioavailable azaindole hydroxamic acids that were potent inhibitors of the HIV-1 IN enzyme. Here we disclose the design and synthesis of novel tricyclic N-hydroxy-dihydronaphthyridinones as potent, orally bioavailable HIV-1 integrase inhibitors displaying excellent ligand and lipophilic efficiencies.

  DOI：

  10.1021/jm200208d