3-(4-fluorobenzyl)-1-(3-[(tetrahydro-2H-pyran-4-yl)oxy]-1-propyn-1-yl)-7-{[2-(trimethylsilyl)ethoxy]methoxy}-3,7,8,9-tetrahydro-6H-pyrrolo[2,3-c]-1,7-naphthyridin-6-one | 1293388-27-8

• 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: 3-(4-fluorobenzyl)-1-(3-[(tetrahydro-2H-pyran-4-yl)oxy]-1-propyn-1-yl)-7-{[2-(trimethylsilyl)ethoxy]methoxy}-3,7,8,9-tetrahydro-6H-pyrrolo[2,3-c]-1,7-naphthyridin-6-one
• 英文别名: 3-[(4-Fluorophenyl)methyl]-1-[3-(oxan-4-yloxy)prop-1-ynyl]-7-(2-trimethylsilylethoxymethoxy)-8,9-dihydropyrrolo[2,3-c][1,7]naphthyridin-6-one
• CAS: 1293388-27-8
• 化学式: C₃₁H₃₈FN₃O₅Si
• 分子量: 579.744
• InChiKey: VIGGYSFCQZTGEO-UHFFFAOYSA-N

物化性质

• 沸点：
  748.3±60.0 °C(predicted)
• 密度：
  1.21±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.01
• 重原子数：
  41
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  75
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-(4-fluorobenzyl)-1-(3-[(tetrahydro-2H-pyran-4-yl)oxy]-1-propyn-1-yl)-7-{[2-(trimethylsilyl)ethoxy]methoxy}-3,7,8,9-tetrahydro-6H-pyrrolo[2,3-c]-1,7-naphthyridin-6-one 在 氢气 、 palladium(II) hydroxide 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以60%的产率得到3-(4-fluorobenzyl)-1-(3-(tetrahydro-2H-pyran-4-yl)oxypropyl)-7-{[2-(trimethylsilyl)ethoxy]methoxy}-3,7,8,9-tetrahydro-6H-pyrrolo[2,3-c]-1,7-naphthyridin-6-one
  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 bis-triphenylphosphine-palladium(II) chloride 、 N-碘代丁二酰亚胺 、 copper(l) iodide 、 sodium cyanoborohydride 、 对甲苯磺酸 、 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 63.0h， 生成 3-(4-fluorobenzyl)-1-(3-[(tetrahydro-2H-pyran-4-yl)oxy]-1-propyn-1-yl)-7-{[2-(trimethylsilyl)ethoxy]methoxy}-3,7,8,9-tetrahydro-6H-pyrrolo[2,3-c]-1,7-naphthyridin-6-one
  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