3-[1-(4-Fluoro-phenyl)-meth-(Z)-ylidene]-5-isobutyl-1-methoxymethoxy-3H-pyrazine-2,6-dione | 179678-80-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 3-[1-(4-Fluoro-phenyl)-meth-(Z)-ylidene]-5-isobutyl-1-methoxymethoxy-3H-pyrazine-2,6-dione
• 英文别名: (3Z)-3-[(4-fluorophenyl)methylidene]-1-(methoxymethoxy)-5-(2-methylpropyl)pyrazine-2,6-dione
• CAS: 179678-80-9
• 化学式: C₁₇H₁₉FN₂O₄
• 分子量: 334.347
• InChiKey: OHMKLCYSFXRUPW-DHDCSXOGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  68.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-[1-(4-Fluoro-phenyl)-meth-(Z)-ylidene]-5-isobutyl-1-methoxymethoxy-3H-pyrazine-2,6-dione 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， 反应 0.33h， 以6.1 mg的产率得到1-hydroxy-3-isobutyl-5-Z-p-fluorobenzylpiperazine-2,6-dione
  参考文献：
  名称：

  Synthesis of Natural Flutimide and Analogous Fully Substituted Pyrazine-2,6-diones, Endonuclease Inhibitors of Influenza Virus

  摘要：

  Flutimide, a fully substituted 1-hydroxy-3H-pyrazine-2,6-dione, is a fungal metabolite isolated from a new species of Delitschia. cofertaspora. It has been shown to selectively inhibit cap-dependent endonuclease activity of influenza virus A. The inhibition of this activity is a target for the potential development of a therapeutic agent to treat influenza infections. A convergent total synthesis of flutimide starting from L-leucine has been described. The synthetic methodology has been extended to include the synthesis of specifically designed aromatic analogues of flutimide, some of which exhibited greater than 7-fold improvement in activity, The most potent compounds were those with p-fluorobenzylidene or p-methoxybenzylidene substitutions at C-5 of 3H-pyrazine-2,6-dione and showed IC50 values of 0.9 and 0.8 muM, respectively. The details of the rationale for the synthetic design, syntheses, and biological activities of these analogues are described.

  DOI：

  10.1021/jo015665d
• 作为产物：
  描述：

  1-methoxymethoxy-3S-isobutyl-4-p-methoxybenzylpiperazine-2,6-dione 在 4-二甲氨基吡啶 、 N,N-二异丙基乙胺 、 2,3-二氯-5,6-二氰基-1,4-苯醌 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 六甲基磷酰三胺 、 二氯甲烷 、 水 为溶剂， 反应 5.0h， 生成 3-[1-(4-Fluoro-phenyl)-meth-(Z)-ylidene]-5-isobutyl-1-methoxymethoxy-3H-pyrazine-2,6-dione
  参考文献：
  名称：

  Synthesis of Natural Flutimide and Analogous Fully Substituted Pyrazine-2,6-diones, Endonuclease Inhibitors of Influenza Virus

  摘要：

  Flutimide, a fully substituted 1-hydroxy-3H-pyrazine-2,6-dione, is a fungal metabolite isolated from a new species of Delitschia. cofertaspora. It has been shown to selectively inhibit cap-dependent endonuclease activity of influenza virus A. The inhibition of this activity is a target for the potential development of a therapeutic agent to treat influenza infections. A convergent total synthesis of flutimide starting from L-leucine has been described. The synthetic methodology has been extended to include the synthesis of specifically designed aromatic analogues of flutimide, some of which exhibited greater than 7-fold improvement in activity, The most potent compounds were those with p-fluorobenzylidene or p-methoxybenzylidene substitutions at C-5 of 3H-pyrazine-2,6-dione and showed IC50 values of 0.9 and 0.8 muM, respectively. The details of the rationale for the synthetic design, syntheses, and biological activities of these analogues are described.

  DOI：

  10.1021/jo015665d