N⁶-(trans-3-phenyl-2-propen-1-yl)adenosine

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: N⁶-(trans-3-phenyl-2-propen-1-yl)adenosine
• 英文别名: n6-(trans-3-Phenyl-2-propen-1-yl)-adenosine；(2R,3S,4R,5R)-2-(hydroxymethyl)-5-[6-[[(E)-3-phenylprop-2-enyl]amino]purin-9-yl]oxolane-3,4-diol
• 化学式: C₁₉H₂₁N₅O₄
• 分子量: 383.407
• InChiKey: MDCJCFWFEUKYAR-DXJMOCTRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  126
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  在 正丙胺 作用下， 以 甲醇 为溶剂， 生成 N⁶-(trans-3-phenyl-2-propen-1-yl)adenosine
  参考文献：
  名称：

  New tools in nucleoside toolbox of tick-borne encephalitis virus reproduction inhibitors

  摘要：

  Design and development of nucleoside analogs is an established strategy in the antiviral drug discovery field. Nevertheless, for many viruses the coverage of structure-activity relationships (SAR) in the nucleoside chemical space is not sufficient. Here we present the nucleoside SAR exploration for tick-borne encephalitis virus (TBEV), a member of Flavivirus genus. Promising antiviral activity may be achieved by introduction of large hydrophobic substituents in the position 6 of adenosine or bulky silyl groups to the position 5'. Introduction of methyls to the ribose moiety does not lead to inhibition of TBEV reproduction. Possible mechanisms of action of these nucleosides include the inhibition of viral entry or interaction with TBEV non-structural protein 5 methyltransferase or RNA-dependent RNA polymerase domains. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.01.040

文献信息

• Modification of the length and structure of the linker of N6-benzyladenosine modulates its selective antiviral activity against enterovirus 71
  作者：Mikhail S. Drenichev、Vladimir E. Oslovsky、Liang Sun、Aloys Tijsma、Nikolay N. Kurochkin、Vitali I. Tararov、Alexander O. Chizhov、Johan Neyts、Christophe Pannecouque、Pieter Leyssen、Sergey N. Mikhailov

  DOI：10.1016/j.ejmech.2016.01.036

  日期：2016.3

  high yields. Analysis of the structure-activity relationship clearly shows that the optimal size of the linker is limited to 2 or 3 atoms (compounds 4–7). 2′-Deoxyadenosine derivatives did not elicit any inhibitory or cytotoxic effect, while 5′-deoxynucleosides still induced some cell protective antiviral activity. Based on these observations, it can be hypothesized that there may be another mechanism

  最近，我们证明了N 6-异戊烯基腺苷，一种细胞分裂素核苷，对人肠病毒71的复制具有有效的选择性抗病毒作用。本研究致力于另一种天然化合物N 6-苄基腺苷的结构优化。我们主要研究腺嘌呤和苯环之间连接基的大小和性质，以及D-核糖残基的必要性。制备了30多种N 6-苄基腺苷类似物，并评估了它们的抗病毒特性。两种主要的制备方法：N 6-乙酰基-2'，3'，5'-tri- O-乙酰基腺苷可以在碱促进条件下通过烷基卤或在Mitsunobu反应中通过醇进行区域选择性烷基化。在室温下用4 M PrNH 2在MeOH中的溶液脱酰1天后，以高总收率获得所需产物。对结构-活性关系的分析清楚地表明，连接子的最佳尺寸限于2或3个原子（化合物4 – 7）。2'-脱氧腺苷衍生物没有引起任何抑制或细胞毒性作用，而5'-脱氧核苷仍然诱导了某些细胞保护性抗病毒活性。基于这些观察，可以假设除了可能的5'-三磷酸化继之以对RNA合
• New tools in nucleoside toolbox of tick-borne encephalitis virus reproduction inhibitors
  作者：Alexey A. Orlov、Mikhail S. Drenichev、Vladimir E. Oslovsky、Nikolay N. Kurochkin、Pavel N. Solyev、Liubov I. Kozlovskaya、Vladimir A. Palyulin、Galina G. Karganova、Sergey N. Mikhailov、Dmitry I. Osolodkin

  DOI：10.1016/j.bmcl.2017.01.040

  日期：2017.3

  Design and development of nucleoside analogs is an established strategy in the antiviral drug discovery field. Nevertheless, for many viruses the coverage of structure-activity relationships (SAR) in the nucleoside chemical space is not sufficient. Here we present the nucleoside SAR exploration for tick-borne encephalitis virus (TBEV), a member of Flavivirus genus. Promising antiviral activity may be achieved by introduction of large hydrophobic substituents in the position 6 of adenosine or bulky silyl groups to the position 5'. Introduction of methyls to the ribose moiety does not lead to inhibition of TBEV reproduction. Possible mechanisms of action of these nucleosides include the inhibition of viral entry or interaction with TBEV non-structural protein 5 methyltransferase or RNA-dependent RNA polymerase domains. (C) 2017 Elsevier Ltd. All rights reserved.