3-(4-fluorobenzyl)-1-(3-hydroxy-3-methylbutyl)-7-((2-(trimethylsilyl)ethoxy)methoxy)-8,9-dihydro-3H-pyrrolo[2,3-c][1,7]naphthyridin-6(7H)-one | 1293388-53-0

• 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-hydroxy-3-methylbutyl)-7-((2-(trimethylsilyl)ethoxy)methoxy)-8,9-dihydro-3H-pyrrolo[2,3-c][1,7]naphthyridin-6(7H)-one
• 英文别名: 3-[(4-Fluorophenyl)methyl]-1-(3-hydroxy-3-methylbutyl)-7-(2-trimethylsilylethoxymethoxy)-8,9-dihydropyrrolo[2,3-c][1,7]naphthyridin-6-one
• CAS: 1293388-53-0
• 化学式: C₂₈H₃₈FN₃O₄Si
• 分子量: 527.711
• InChiKey: IEKRPUBHNWYGPC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.17
• 重原子数：
  37
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  76.8
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-(4-fluorobenzyl)-1-(3-hydroxy-3-methylbutyl)-7-((2-(trimethylsilyl)ethoxy)methoxy)-8,9-dihydro-3H-pyrrolo[2,3-c][1,7]naphthyridin-6(7H)-one 在 吡啶 、 氢氟酸 、 水 、 碳酸氢钠 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 4.0h， 以39%的产率得到3-(4-fluorobenzyl)-7-hydroxy-1-(3-hydroxy-3-methylbutyl)-8,9-dihydro-3H-pyrrolo[2,3-c][1,7]naphthyridin-6(7H)-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 、 氢气 、 palladium(II) hydroxide 、 sodium cyanoborohydride 、 对甲苯磺酸 、 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 65.0h， 生成 3-(4-fluorobenzyl)-1-(3-hydroxy-3-methylbutyl)-7-((2-(trimethylsilyl)ethoxy)methoxy)-8,9-dihydro-3H-pyrrolo[2,3-c][1,7]naphthyridin-6(7H)-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

文献信息

• Design and Synthesis of Novel <i>N</i>-Hydroxy-Dihydronaphthyridinones as Potent and Orally Bioavailable HIV-1 Integrase Inhibitors
  作者：Ted W. Johnson、Steven P. Tanis、Scott L. Butler、Deepak Dalvie、Dorothy M. DeLisle、Klaus R. Dress、Erik J. Flahive、Qiyue Hu、Jon E. Kuehler、Atsuo Kuki、Wen Liu、Guy A. McClellan、Qinghai Peng、Michael B. Plewe、Paul F. Richardson、Graham L. Smith、Jim Solowiej、Khanh T. Tran、Hai Wang、Xiaoming Yu、Junhu Zhang、Huichun Zhu

  DOI：10.1021/jm200208d

  日期：2011.5.12

  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.