[[(4R,5R,6R,8R)-8-(2-amino-6-oxo-1H-purin-9-yl)-5-hydroxy-3,7-dioxaspiro[3.4]octan-6-yl]methoxy-hydroxy-phosphoryl] phosphono hydrogen phosphate | 1469985-01-0

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷酸
• 英文名称: [[(4R,5R,6R,8R)-8-(2-amino-6-oxo-1H-purin-9-yl)-5-hydroxy-3,7-dioxaspiro[3.4]octan-6-yl]methoxy-hydroxy-phosphoryl] phosphono hydrogen phosphate
• 英文别名: [[(4R,5R,6R,8R)-8-(2-amino-6-oxo-1H-purin-9-yl)-5-hydroxy-1,7-dioxaspiro[3.4]octan-6-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate
• CAS: 1469985-01-0
• 化学式: C₁₂H₁₈N₅O₁₄P₃
• 分子量: 549.221
• InChiKey: OZJJRKVOISYTCX-GSWPYSDESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -6.1
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  284
• 氢给体数：
  7
• 氢受体数：
  16

反应信息

• 作为产物：
  描述：

  (2R,3R,4R,5R)-3-allyl-2-(2-amino-6-chloro-9H-purin-9-yl)-5-((benzoyloxy)methyl)tetrahydrofuran-3,4-diyl dibenzoate 在 吡啶 、 N,N-二甲基丙烯基脲 、 氟化铵 、 sodium tetrahydroborate 、 sodium periodate 、 四氧化锇 、 三正丁胺 、 sodium methylate 、 sodium hydride 、 三丁基焦磷酸铵 、 N-甲基吗啉氧化物 、 adenosine deaminase 、 三氯氧磷 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 水 、 乙酸乙酯 、 mineral oil 、 叔丁醇 为溶剂， 反应 142.0h， 生成 [[(4R,5R,6R,8R)-8-(2-amino-6-oxo-1H-purin-9-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.