ethyl (2S)-2-{[(4aR,6R,7R,7aR)-7-hydroxy-7-methyl-2-oxo-6-(2-oxo-4-[(2-propylpentanoyl)amino]pyrimidin-1(2H)-yl)-tetrahydro-4H-furo[3,2-d][1,3,2]dioxaphosphinin-2-yl]amino}butanoate | 1035637-98-9

• 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: ethyl (2S)-2-{[(4aR,6R,7R,7aR)-7-hydroxy-7-methyl-2-oxo-6-(2-oxo-4-[(2-propylpentanoyl)amino]pyrimidin-1(2H)-yl)-tetrahydro-4H-furo[3,2-d][1,3,2]dioxaphosphinin-2-yl]amino}butanoate
• 英文别名: Ethyl (2S)-2-({(4aR,6R,7R,7aR)-7-hydroxy-7-methyl-2-oxido-6-[2-oxo-4-[(2-propylpentanoyl)amino]pyrimidin-1(2H)-yl]tetrahydro-4H-furo[3,2-d][1,3,2]dioxaphosphinin-2-yl}amino)butanoate；ethyl (2S)-2-[[(4aR,6R,7R,7aR)-7-hydroxy-7-methyl-2-oxo-6-[2-oxo-4-(2-propylpentanoylamino)pyrimidin-1-yl]-4,4a,6,7a-tetrahydrofuro[3,2-d][1,3,2]dioxaphosphinin-2-yl]amino]butanoate
• CAS: 1035637-98-9
• 化学式: C₂₄H₃₉N₄O₉P
• 分子量: 558.569
• InChiKey: LFZGMLQYXWVUAK-RIYWJXHSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  38
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  165
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  2,2-二-正丙基乙酰基氯 、 ethyl (2S)-2-{[(4aR,6R,7R,7aR)-6-(4-amino-2-oxopyrimidin-1(2H)-yl)-7-hydroxy-7-methyl-2-oxotetrahydro-4H-furo[3,2-d][1,3,2]dioxaphosphinin-2-yl]amino}butanoate 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以36%的产率得到ethyl (2S)-2-{[(4aR,6R,7R,7aR)-7-hydroxy-7-methyl-2-oxo-6-(2-oxo-4-[(2-propylpentanoyl)amino]pyrimidin-1(2H)-yl)-tetrahydro-4H-furo[3,2-d][1,3,2]dioxaphosphinin-2-yl]amino}butanoate
  参考文献：
  名称：

  WO2008/79206

  摘要：

  公开号：

文献信息

• NUCLEOSIDE CYCLIC PHOSPHORAMIDATES FOR THE TREATMENT OF RNA-DEPENDENT RNA VIRAL INFECTION
  申请人：Meppen Malte

  公开号：US20100022468A1

  公开（公告）日：2010-01-28

  The present invention provides nucleoside cyclic phosphoramidates of structural formula (I) which are precursors to inhibitors of RNA-dependent RNA viral polymerase. These compounds are precursors to inhibitors of RNA-dependent RNA viral replication and are useful for the treatment of RNA-dependent RNA viral infection. They are particularly useful as pre-cursors to inhibitors of hepatitis C virus (HCV) NS5B polymerase, as precursors to inhibitors of HCV replication, and/or for the treatment of hepatitis C infection. The invention also describes pharmaceutical compositions containing such nucleoside cyclic phosphoramidates alone or in combination with other agents active against RNA-dependent RNA viral infection, in particular HCV infection. Also disclosed are methods of inhibiting RNA-dependent RNA polymerase, inhibiting RNA-dependent RNA viral replication, and/or treating RNA-dependent RNA viral infection with the nucleoside cyclic phosphoramidates of the present invention.

  本发明提供了结构式（I）的核苷酸环磷酰胺，它们是RNA依赖性RNA病毒聚合酶抑制剂的前体。这些化合物是RNA依赖性RNA病毒复制的抑制剂的前体，并且可用于治疗RNA依赖性RNA病毒感染。它们特别适用于作为丙型肝炎病毒（HCV）NS5B聚合酶抑制剂的前体，作为HCV复制抑制剂的前体和/或用于治疗丙型肝炎感染。本发明还描述了仅含有这种核苷酸环磷酰胺或与其他对RNA依赖性RNA病毒感染，特别是HCV感染活性的药物组合的制药组合物。本发明还公开了使用本发明的核苷酸环磷酰胺抑制RNA依赖性RNA聚合酶，抑制RNA依赖性RNA病毒复制和/或治疗RNA依赖性RNA病毒感染的方法。
• Nucleoside cyclic phosphoramidates for the treatment of RNA-dependent RNA viral infection
  申请人：Istituto di Ricerche di Biologia Molecolare P. Angeletti S.P.A.

  公开号：US08148349B2

  公开（公告）日：2012-04-03

  The present invention provides nucleoside cyclic phosphoramidates of formula (I), pharmaceutical compositions comprising the compounds of formula (I) and methods of inhibiting RNA-dependent RNA polymerase, inhibiting RNA-dependent RNA viral replication, and/or treating RNA-dependent RNA viral infection using the compounds of formula (I).

  本发明提供了式(I)的核苷酸环磷酰胺，包括式(I)化合物的制药组合物以及使用式(I)化合物抑制RNA依赖性RNA聚合酶，抑制RNA依赖性RNA病毒复制和/或治疗RNA依赖性RNA病毒感染的方法。
• US8148349B2
  申请人：——

  公开号：US8148349B2

  公开（公告）日：2012-04-03
• [EN] NUCLEOSIDE CYCLIC PHOSPHORAMIDATES FOR THE TREATMENT OF RNA-DEPENDENT RNA VIRAL INFECTION<br/>[FR] PHOSPHORAMIDATES CYCLIQUES NUCLÉOSIDIQUES POUR LE TRAITEMENT D'INFECTIONS VIRALES ARN DÉPENDANTES
  申请人：MERCK & CO INC

  公开号：WO2008079206A1

  公开（公告）日：2008-07-03

  [EN] The present invention provides nucleoside cyclic phosphoramidates of structural formula (I) which are precursors to inhibitors of RNA-dependent RNA viral polymerase. These compounds are precursors to inhibitors of RNA-dependent RNA viral replication and are useful for the treatment of RNA-dependent RNA viral infection. They are particularly useful as precursors to inhibitors of hepatitis C virus (HCV) NS5B polymerase, as precursors to inhibitors of HCV replication, and/or for the treatment of hepatitis C infection. The invention also describes pharmaceutical compositions containing such nucleoside cyclic phosphoramidates alone or in combination with other agents active against RNA-dependent RNA viral infection, in particular HCV infection. Also disclosed are methods of inhibiting RNA-dependent RNA polymerase, inhibiting RNA-dependent RNA viral replication, and/or treating RNA-dependent RNA viral infection with the nucleoside cyclic phosphoramidates of the present invention. (I),
  [FR] La présente invention a trait à des phosphoramidates cycliques nucléosidiques de formule structurale (I) qui sont des précurseurs d'inhibiteurs de l'ARN polymérase virale ARN dépendante. Ces composés sont des précurseurs d'inhibiteurs de la réplication virale ARN ARN dépendante et sont utiles dans le traitement d'infections virales ARN dépendantes. Plus concrètement, ces composés sont utiles en tant que précurseurs d'inhibiteurs de la polymérase NS5B du virus de l'hépatite C (VHC), en tant que précurseurs d'inhibiteurs de la réplication de VHC et/ou dans le traitement de l'infection par l'hépatite C. L'invention a également trait à des compositions pharmaceutiques contenant lesdits phosphoramidates cycliques nucléosidiques seuls ou combinés avec d'autres agents actifs contre l'infection virale de l'ARN ARN dépendante, notamment l'infection par le VHC. Font en outre l'objet de la présente invention des procédés d'inhibition de l'ARN polymérase ARN dépendante, d'inhibition de la réplication virale d'ARN ARN dépendante et/ou de traitement de l'infection virale d'ARN ARN dépendante grâce aux phosphoramidates cycliques nucléosidiques de la présente invention. (I),