2-amino-9-((1R,3R,4R,7S)-7-hydroxy-1-(1-hydroxyethyl)-2,5-dioxabicyclo[2.2.1]heptan-3-yl)-1H-purin-6(9H)-one | 1610605-65-6

• 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: 2-amino-9-((1R,3R,4R,7S)-7-hydroxy-1-(1-hydroxyethyl)-2,5-dioxabicyclo[2.2.1]heptan-3-yl)-1H-purin-6(9H)-one
• CAS: 1610605-65-6
• 化学式: C₁₂H₁₅N₅O₅
• 分子量: 309.282
• InChiKey: XVTBRCBZUBYPBW-MQYGFGHXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.89
• 重原子数：
  22.0
• 可旋转键数：
  2.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  148.51
• 氢给体数：
  4.0
• 氢受体数：
  9.0

反应信息

• 作为产物：
  描述：

  (1R,3R,4R,7S)-7-benzyloxy-1-methanesulfonyloxymethyl-3-(guanin-9-yl)-2,5-dioxabicyclo[2.2.1]heptane 在 吡啶 、 盐酸 、 4-二甲氨基吡啶 、 甲酸 、 10 wt% Pd(OH)2 on carbon 、 氨 、 乙酸酐 、 二甲基亚砜 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 吡啶 、 甲醇 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 267.0h， 生成 2-amino-9-((1R,3R,4R,7S)-7-hydroxy-1-(1-hydroxyethyl)-2,5-dioxabicyclo[2.2.1]heptan-3-yl)-1H-purin-6(9H)-one
  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

文献信息

• Synthesis of 2′-O,4′-C-alkylene-bridged ribonucleosides and their evaluation as inhibitors of HCV NS5B polymerase
  作者：Christopher Chapron、Rebecca Glen、Massimiliano La Colla、Benjamin A. Mayes、Joseph F. McCarville、Stephen Moore、Adel Moussa、Ruhul Sarkar、Maria Seifer、Ilaria Serra、Alistair Stewart

  DOI：10.1016/j.bmcl.2014.04.050

  日期：2014.6

  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.