N-(9-((1R,3R,4R,7S)-7-(benzyloxy)-1-((R)-1-hydroxyethyl)-2,5-dioxabicyclo[2.2.1]heptan-3-yl)-6-oxo-6,9-dihydro-1H-purin-2-yl)benzamide | 1610605-79-2

• 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: N-(9-((1R,3R,4R,7S)-7-(benzyloxy)-1-((R)-1-hydroxyethyl)-2,5-dioxabicyclo[2.2.1]heptan-3-yl)-6-oxo-6,9-dihydro-1H-purin-2-yl)benzamide
• CAS: 1610605-79-2
• 化学式: C₂₆H₂₅N₅O₆
• 分子量: 503.514
• InChiKey: AERIICABRDMVOM-SEJJEVORSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.0
• 重原子数：
  37.0
• 可旋转键数：
  7.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  140.59
• 氢给体数：
  3.0
• 氢受体数：
  9.0

反应信息

• 作为产物：
  描述：

  N-(9-((1S,3R,4R,7S)-7-(benzyloxy)-1-(hydroxymethyl)-2,5-dioxabicyclo[2.2.1]heptan-3-yl)-6-oxo-6,9-dihydro-1H-purin-2-yl)benzamide 、 甲基溴化镁 在 乙酸酐 、 二甲基亚砜 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 3.5h， 以11%的产率得到N-(9-((1R,3R,4R,7S)-7-(benzyloxy)-1-((R)-1-hydroxyethyl)-2,5-dioxabicyclo[2.2.1]heptan-3-yl)-6-oxo-6,9-dihydro-1H-purin-2-yl)benzamide
  参考文献：
  名称：

  Synthesis of 2′-O,4′-C-alkylene-bridged ribonucleosides and their evaluation as inhibitors of HCV NS5B polymerase

  摘要：

  The synthesis of 2'-O,4'-C-methylene-bridged bicyclic guanine ribonucleosides bearing 2'-C-methyl or 5'C-methyl modifications is described. Key to the successful installation of the methyl functionality in both cases was the use of a one-pot oxidation-Grignard procedure to avoid formation of the respective unreactive hydrates prior to alkylation. The 2'-C-methyl- and 5'-C-methyl-modified bicyclic guanosines were evaluated, along with the known uracil-, cytosine-, adenine-, guanine-LNA and guanine-ENA nucleosides, as potential antiviral agents and found to be inactive in the hepatitis C virus (HCV) cell-based replicon assay. Examination of the corresponding nucleoside triphosphates, however, against the purified HCV NS5B polymerase indicated that LNA-G and 2'-C-methyl-LNA-G are potent inhibitors of both 1b wild type and S282T mutant enzymes in vitro. Activity was further demonstrated for the LNA-G-triphosphate against HCV NS5B polymerase genotypes 1a, 2a, 3a and 4a. A phosphorylation by-pass prodrug strategy may be required to promote anti-HCV activity in the replicon assay. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.04.050