(2S)-methyl 2-(((((5S,6R,8R,9R)-6-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-9-hydroxy-1,7-dioxaspiro[4.4]nonan-8-yl)methoxy)(phenoxy)phosphoryl)amino)propanoate | 1378912-66-3

• 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: (2S)-methyl 2-(((((5S,6R,8R,9R)-6-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-9-hydroxy-1,7-dioxaspiro[4.4]nonan-8-yl)methoxy)(phenoxy)phosphoryl)amino)propanoate
• 英文别名: methyl (2S)-2-[[[(5S,6R,7R,9R)-9-(2,4-dioxopyrimidin-1-yl)-6-hydroxy-4,8-dioxaspiro[4.4]nonan-7-yl]methoxy-phenoxy-phosphoryl]amino]propanoate；methyl (2S)-2-[[[(5S,6R,8R,9R)-6-(2,4-dioxopyrimidin-1-yl)-9-hydroxy-1,7-dioxaspiro[4.4]nonan-8-yl]methoxy-phenoxyphosphoryl]amino]propanoate
• CAS: 1378912-66-3
• 化学式: C₂₂H₂₈N₃O₁₀P
• 分子量: 525.452
• InChiKey: VVQWVZUPTGFPIH-YMGVOGLASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  36
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  162
• 氢给体数：
  3
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  1-[2-O,2-C-propano-3,5-di-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-β-D-arabinofuranosyl]uracil 在 N-甲基咪唑 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 (2S)-methyl 2-(((((5S,6R,8R,9R)-6-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-9-hydroxy-1,7-dioxaspiro[4.4]nonan-8-yl)methoxy)(phenoxy)phosphoryl)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

• [EN] COMPOUNDS<br/>[FR] COMPOSÉS
  申请人：PHARMASSET INC

  公开号：WO2012075140A1

  公开（公告）日：2012-06-07

  Disclosed herein are 2'-spiro-nucleosides of formula I and derivatives thereof useful for treating a subject infected by hepatitis C virus or dengue virus. Formula (I), where z is a four-or five-membered ring selected from among radicals a-o represented by de following structures (II) where * represents the point of attachment to the 2'-carbon.

  本文披露了公式I的2'-螺环核苷及其衍生物，用于治疗感染丙型肝炎病毒或登革病毒的受试者。公式(I)中，z是从以下结构(II)所代表的基团a-o中选择的四元或五元环。其中*表示连接到2'-碳的位置。
• COMPOUNDS
  申请人：DU JINFA

  公开号：US20120142626A1

  公开（公告）日：2012-06-07

  Disclosed herein are 2′-spiro-nucleosides and derivatives thereof useful for treating a subject infected by hepatitis C virus or dengue virus.

  本文公开了2'-螺环核苷及其衍生物，用于治疗感染丙型肝炎病毒或登革热病毒的患者。
• 2'-SPIRO-NUCLEOSIDES FOR USE IN THE THERAPY OF HEPATITIS C
  申请人：Gilead Pharmasset LLC

  公开号：EP3042910B1

  公开（公告）日：2019-01-09
• US8841275B2
  申请人：——

  公开号：US8841275B2

  公开（公告）日：2014-09-23
• US9394331B2
  申请人：——

  公开号：US9394331B2

  公开（公告）日：2016-07-19