(5Z)-3-isobutyl-1-(methoxymethoxy)-5-(2-methylpropylidene)pyrazine-2,6-dione | 162715-78-8

• 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: (5Z)-3-isobutyl-1-(methoxymethoxy)-5-(2-methylpropylidene)pyrazine-2,6-dione
• 英文别名: (5Z)-1-(methoxymethoxy)-3-(2-methylpropyl)-5-(2-methylpropylidene)pyrazine-2,6-dione
• CAS: 162715-78-8
• 化学式: C₁₄H₂₂N₂O₄
• 分子量: 282.34
• InChiKey: SPNZLGIPSZGSEQ-WDZFZDKYSA-N

物化性质

• 沸点：
  349.5±44.0 °C(Predicted)
• 密度：
  1.13±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  68.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (5Z)-3-isobutyl-1-(methoxymethoxy)-5-(2-methylpropylidene)pyrazine-2,6-dione 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 (5Z)-1-羟基-3-(2-甲基丙基)-5-(2-甲基丙亚基)吡嗪-2,6-二酮
  参考文献：
  名称：

  Total synthesis of flutimide, a novel endonuclease inhibitor of influenza virus

  摘要：

  Flutimide is a completely substituted 1-N-hydroxy-2,6-diketo-Delta 3-piperazine isolated from a new species of Delitschia cofertaspora. It selectively inhibits influenza virus A endonuclease activity without affecting any viral transcription activity. Total synthesis of flutimide starting from L-leucine has been described.

  DOI：

  10.1016/0040-4039(95)00214-w
• 作为产物：
  描述：

  N-p-methoxybenzyl-N-(1-tert-butoxy-acet-2-yl)-(S)-leucine methyl ester 在 4-二甲氨基吡啶 、 TEA 、 羟胺 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 N,N-二异丙基乙胺 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 、 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 、 乙醇 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 100.0h， 生成 (5Z)-3-isobutyl-1-(methoxymethoxy)-5-(2-methylpropylidene)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

文献信息

• Synthesis of Natural Flutimide and Analogous Fully Substituted Pyrazine-2,6-diones, Endonuclease Inhibitors of Influenza Virus
  作者：Sheo B. Singh、Joanne E. Tomassini

  DOI：10.1021/jo015665d

  日期：2001.8.1

  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.
• Total synthesis of flutimide, a novel endonuclease inhibitor of influenza virus
  作者：Sheo B. Singh

  DOI：10.1016/0040-4039(95)00214-w

  日期：1995.3

  Flutimide is a completely substituted 1-N-hydroxy-2,6-diketo-Delta 3-piperazine isolated from a new species of Delitschia cofertaspora. It selectively inhibits influenza virus A endonuclease activity without affecting any viral transcription activity. Total synthesis of flutimide starting from L-leucine has been described.