N-(4-hydroxybutyl) 3-(pivaloyloxymethyl)-5-(perylen-3-ylethynyl)uracil-1-acetamide

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: N-(4-hydroxybutyl) 3-(pivaloyloxymethyl)-5-(perylen-3-ylethynyl)uracil-1-acetamide
• 英文别名: 3-Pivaloyloxymethyl-5-(perylen-3-ylethynyl)-uracil-1-acetic acid, 4-oxybutylamide；[3-[2-(4-hydroxybutylamino)-2-oxoethyl]-2,6-dioxo-5-(2-perylen-3-ylethynyl)pyrimidin-1-yl]methyl 2,2-dimethylpropanoate
• 化学式: C₃₈H₃₅N₃O₆
• 分子量: 629.712
• InChiKey: WKUDOIRAAWUKPC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  47
• 可旋转键数：
  12
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  116
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-(4-hydroxybutyl) 3-(pivaloyloxymethyl)-5-(perylen-3-ylethynyl)uracil-1-acetamide 在 sodium hydroxide 作用下， 以 甲醇 、 水 、 二甲基亚砜 为溶剂， 反应 0.25h， 以52%的产率得到N-(4-hydroxybutyl) 5-(perylen-3-ylethynyl)uracil-1-acetamide
  参考文献：
  名称：

  Compounds based on 5-(perylen-3-ylethynyl)uracil scaffold: High activity against tick-borne encephalitis virus and non-specific activity against enterovirus A

  摘要：

  Rigid amphipathic fusion inhibitors (RAFIs) are potent antivirals based on a perylene core linked with a nucleoside moiety. Sugar-free analogues of RAFIs, 5-(perylen-3-ylethynyl)uracil-1-acetic acid 1 and its amides 2, were synthesized using combined protection group strategy. Compounds 1 and 2 appeared to have low toxicity on porcine embryo kidney (PEK) or rhabdomiosarcoma (RD) cells together with remarkable activity against enveloped tick-borne encephalitis virus (TBEV): EC50 values vary from 0.077 mu M to subnanomolar range. Surprisingly, 3-pivaloyloxymethyl (Pom) protected precursors 7 and 8 showed even more pronounced activity. All the compounds showed no activity against several non enveloped enteroviruses, except 4-hydroxybutylamides 2d,g, which inhibited the reproduction of enterovirus A71 with EC50 50-100 mu M, with a non-specific mode of action. The results suggest that the carbohydrate moiety of RAFI nucleosides does not play a crucial role in their antiviral action, and biological activity of the 5-(perylen-3-ylethynyl)uracil scaffold can be effectively modulated by substituents in positions 1 and 3. The high antiviral activity of these new compounds, coupled with low toxicity advocate their potential role in antiviral therapy. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.03.029
• 作为产物：
  描述：

  tert-butyl (5-iodouracil-1-yl)acetate 在 copper(l) iodide 、 四(三苯基膦)钯 、 甲酸 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 potassium carbonate 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 N-(4-hydroxybutyl) 3-(pivaloyloxymethyl)-5-(perylen-3-ylethynyl)uracil-1-acetamide
  参考文献：
  名称：

  Compounds based on 5-(perylen-3-ylethynyl)uracil scaffold: High activity against tick-borne encephalitis virus and non-specific activity against enterovirus A

  摘要：

  Rigid amphipathic fusion inhibitors (RAFIs) are potent antivirals based on a perylene core linked with a nucleoside moiety. Sugar-free analogues of RAFIs, 5-(perylen-3-ylethynyl)uracil-1-acetic acid 1 and its amides 2, were synthesized using combined protection group strategy. Compounds 1 and 2 appeared to have low toxicity on porcine embryo kidney (PEK) or rhabdomiosarcoma (RD) cells together with remarkable activity against enveloped tick-borne encephalitis virus (TBEV): EC50 values vary from 0.077 mu M to subnanomolar range. Surprisingly, 3-pivaloyloxymethyl (Pom) protected precursors 7 and 8 showed even more pronounced activity. All the compounds showed no activity against several non enveloped enteroviruses, except 4-hydroxybutylamides 2d,g, which inhibited the reproduction of enterovirus A71 with EC50 50-100 mu M, with a non-specific mode of action. The results suggest that the carbohydrate moiety of RAFI nucleosides does not play a crucial role in their antiviral action, and biological activity of the 5-(perylen-3-ylethynyl)uracil scaffold can be effectively modulated by substituents in positions 1 and 3. The high antiviral activity of these new compounds, coupled with low toxicity advocate their potential role in antiviral therapy. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.03.029

文献信息

• Compounds based on 5-(perylen-3-ylethynyl)uracil scaffold: High activity against tick-borne encephalitis virus and non-specific activity against enterovirus A
  作者：Alexey A. Chistov、Alexey A. Orlov、Philipp P. Streshnev、Nikita A. Slesarchuk、Ilya O. Aparin、Brijesh Rathi、Vladimir A. Brylev、Sergey V. Kutyakov、Irina V. Mikhura、Alexey V. Ustinov、Gunnar Westman、Vladimir A. Palyulin、Nidhi Jain、Dmitry I. Osolodkin、Liubov I. Kozlovskaya、Vladimir A. Korshun

  DOI：10.1016/j.ejmech.2019.03.029

  日期：2019.6

  Rigid amphipathic fusion inhibitors (RAFIs) are potent antivirals based on a perylene core linked with a nucleoside moiety. Sugar-free analogues of RAFIs, 5-(perylen-3-ylethynyl)uracil-1-acetic acid 1 and its amides 2, were synthesized using combined protection group strategy. Compounds 1 and 2 appeared to have low toxicity on porcine embryo kidney (PEK) or rhabdomiosarcoma (RD) cells together with remarkable activity against enveloped tick-borne encephalitis virus (TBEV): EC50 values vary from 0.077 mu M to subnanomolar range. Surprisingly, 3-pivaloyloxymethyl (Pom) protected precursors 7 and 8 showed even more pronounced activity. All the compounds showed no activity against several non enveloped enteroviruses, except 4-hydroxybutylamides 2d,g, which inhibited the reproduction of enterovirus A71 with EC50 50-100 mu M, with a non-specific mode of action. The results suggest that the carbohydrate moiety of RAFI nucleosides does not play a crucial role in their antiviral action, and biological activity of the 5-(perylen-3-ylethynyl)uracil scaffold can be effectively modulated by substituents in positions 1 and 3. The high antiviral activity of these new compounds, coupled with low toxicity advocate their potential role in antiviral therapy. (C) 2019 Elsevier Masson SAS. All rights reserved.