[[(4S,5R,6R,8R)-8-(4-amino-2-oxo-pyrimidin-1-yl)-5-hydroxy-3,7-dioxaspiro[3.4]octan-6-yl]methoxy-hydroxy-phosphoryl] phosphono hydrogen phosphate | 1378913-10-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: [[(4S,5R,6R,8R)-8-(4-amino-2-oxo-pyrimidin-1-yl)-5-hydroxy-3,7-dioxaspiro[3.4]octan-6-yl]methoxy-hydroxy-phosphoryl] phosphono hydrogen phosphate
• 英文别名: [[(4S,5R,6R,8R)-8-(4-amino-2-oxopyrimidin-1-yl)-5-hydroxy-1,7-dioxaspiro[3.4]octan-6-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate
• CAS: 1378913-10-0
• 化学式: C₁₁H₁₈N₃O₁₄P₃
• 分子量: 509.197
• InChiKey: ANWKWICTRAHHJH-AAQQEJRNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -6
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  257
• 氢给体数：
  6
• 氢受体数：
  14

反应信息

• 作为产物：
  描述：

  在 吡啶 、 N,N-二甲基丙烯基脲 、 三正丁胺 、 四丁基氟化铵 、 氨 、 三丁基焦磷酸铵 、 三氯氧磷 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 23.0h， 生成 [[(4S,5R,6R,8R)-8-(4-amino-2-oxo-pyrimidin-1-yl)-5-hydroxy-3,7-dioxaspiro[3.4]octan-6-yl]methoxy-hydroxy-phosphoryl] phosphono hydrogen phosphate
  参考文献：
  名称：

  Use of 2′-Spirocyclic Ethers in HCV Nucleoside Design

  摘要：

  Conformationally restricted 2'-spironucleosides and their prodrugs were synthesized as potential anti-HCV agents. Although the replicon activity of the new agents containing pyrimidine bases was modest, the triphosphate of a 2'-oxetane cytidine analogue demonstrated potent intrinsic biochemical activity against the NS5B polymerase, with IC50 = 8.48 mu M. Activity against NS5B bearing the S282T mutation was reduced. Phosphoramidate prodrugs of a 2'-oxetane 2-amino-6-O-methylpurine nucleoside demonstrated potent anti-HCV activity in vitro, and the corresponding triphosphate retained similar potent activity against both wild-type and S282T HCV NS5B polymerase.

  DOI：

  10.1021/jm401224y

文献信息

• Use of 2′-Spirocyclic Ethers in HCV Nucleoside Design
  作者：Jinfa Du、Byoung-Kwon Chun、Ralph T. Mosley、Shalini Bansal、Haiying Bao、Christine Espiritu、Angela M. Lam、Eisuke Murakami、Congrong Niu、Holly M. Micolochick Steuer、Phillip A. Furman、Michael J. Sofia

  DOI：10.1021/jm401224y

  日期：2014.3.13

  Conformationally restricted 2'-spironucleosides and their prodrugs were synthesized as potential anti-HCV agents. Although the replicon activity of the new agents containing pyrimidine bases was modest, the triphosphate of a 2'-oxetane cytidine analogue demonstrated potent intrinsic biochemical activity against the NS5B polymerase, with IC50 = 8.48 mu M. Activity against NS5B bearing the S282T mutation was reduced. Phosphoramidate prodrugs of a 2'-oxetane 2-amino-6-O-methylpurine nucleoside demonstrated potent anti-HCV activity in vitro, and the corresponding triphosphate retained similar potent activity against both wild-type and S282T HCV NS5B polymerase.