3-(2'-deoxy-β-D-ribofuranosyl)-6-hexyl-2,3-dihydrofuro[2,3-d]pyrimidin-2-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 呋喃[2,3-d]嘧啶
• 英文名称: 3-(2'-deoxy-β-D-ribofuranosyl)-6-hexyl-2,3-dihydrofuro[2,3-d]pyrimidin-2-one
• 英文别名: 6-Hexyl-3-(4-hydroxy-5-hydroxymethyl-tetrahydro-furan-2-yl)-3H-furo[2,3-d]pyrimidin-2-one；6-hexyl-3-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]furo[2,3-d]pyrimidin-2-one
• 化学式: C₁₇H₂₄N₂O₅
• 分子量: 336.388
• InChiKey: MVKQCHZYJORQRZ-RRFJBIMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  91.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1-(2-deoxy-β-D-erythro-pentofuranosyl)-5-(oct-1-ynyl)uracil 在 copper(l) iodide 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 3-(2'-deoxy-β-D-ribofuranosyl)-6-hexyl-2,3-dihydrofuro[2,3-d]pyrimidin-2-one
  参考文献：
  名称：

  Potent and Selective Inhibition of Varicella-Zoster Virus (VZV) by Nucleoside Analogues with an Unusual Bicyclic Base

  摘要：

  We herein report the discovery of an entirely new category of potent antiviral agents based on novel deoxynucleoside analogues with unusual bicyclic base moieties. Target structures, previously known as byproducts in Pd-catalyzed coupling of terminal alkynes with 5-iodo-nucleosides, are recognized herein for the first time to be potent and selective inhibitors of varicella-zoster virus (VZV) in vitro. As an unusual structure-activity relationship we noted the absolute requirement of a long alkyl side chain, with an optimum length of C-8-C-10, for antiviral activity. We thus report the synthesis and characterization of a series of chain-modified analogues and their extensive in vitro evaluation. The lead compounds have a ca. 300-fold enhancement in anti-VZV activity over the reference compound acyclovir, with no detectable in vitro cytotoxicity. The novel structure of these compounds, coupled with their ease of synthesis, excellent antiviral profile, and promising physical properties, makes them of great interest for possible antiviral drug development.

  DOI：

  10.1021/jm990346o

文献信息

• Potent and Selective Inhibition of Varicella-Zoster Virus (VZV) by Nucleoside Analogues with an Unusual Bicyclic Base
  作者：Christopher McGuigan、Christopher J. Yarnold、Garry Jones、Sonsoles Velázquez、Hubert Barucki、Andrea Brancale、Graciela Andrei、Robert Snoeck、Erik De Clercq、Jan Balzarini

  DOI：10.1021/jm990346o

  日期：1999.11.1

  We herein report the discovery of an entirely new category of potent antiviral agents based on novel deoxynucleoside analogues with unusual bicyclic base moieties. Target structures, previously known as byproducts in Pd-catalyzed coupling of terminal alkynes with 5-iodo-nucleosides, are recognized herein for the first time to be potent and selective inhibitors of varicella-zoster virus (VZV) in vitro. As an unusual structure-activity relationship we noted the absolute requirement of a long alkyl side chain, with an optimum length of C-8-C-10, for antiviral activity. We thus report the synthesis and characterization of a series of chain-modified analogues and their extensive in vitro evaluation. The lead compounds have a ca. 300-fold enhancement in anti-VZV activity over the reference compound acyclovir, with no detectable in vitro cytotoxicity. The novel structure of these compounds, coupled with their ease of synthesis, excellent antiviral profile, and promising physical properties, makes them of great interest for possible antiviral drug development.