2,2-dimethylpropyl (2S)-2-[[[(4R,5R,6R,8R)-8-(2-amino-6-methoxypurin-9-yl)-5-hydroxy-1,7-dioxaspiro[3.4]octan-6-yl]methoxy-naphthalen-1-yloxyphosphoryl]amino]propanoate | 1378912-79-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2,2-dimethylpropyl (2S)-2-[[[(4R,5R,6R,8R)-8-(2-amino-6-methoxypurin-9-yl)-5-hydroxy-1,7-dioxaspiro[3.4]octan-6-yl]methoxy-naphthalen-1-yloxyphosphoryl]amino]propanoate
• CAS: 1378912-79-8
• 化学式: C₃₁H₃₉N₆O₉P
• 分子量: 670.659
• InChiKey: VKFVNRIZLNEVPI-NSLZILBFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  47
• 可旋转键数：
  13
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  191
• 氢给体数：
  3
• 氢受体数：
  14

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-甲基咪唑 、 氟化铵 、 sodium tetrahydroborate 、 sodium periodate 、 四氧化锇 、 sodium methylate 、 sodium hydride 、 N-甲基吗啉氧化物 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 97.0h， 生成 2,2-dimethylpropyl (2S)-2-[[[(4R,5R,6R,8R)-8-(2-amino-6-methoxypurin-9-yl)-5-hydroxy-1,7-dioxaspiro[3.4]octan-6-yl]methoxy-naphthalen-1-yloxyphosphoryl]amino]propanoate
  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.