4-amino-1-((4S,5R,7R,8R)-8-hydroxy-7-(hydroxymethyl)-1,6-dioxaspiro[3.4]octan-5-yl)pyrimidin-2(1H)-one | 1378911-71-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-amino-1-((4S,5R,7R,8R)-8-hydroxy-7-(hydroxymethyl)-1,6-dioxaspiro[3.4]octan-5-yl)pyrimidin-2(1H)-one
• 英文别名: 4-amino-1-[(4S,5R,6R,8R)-5-hydroxy-6-(hydroxymethyl)-3,7-dioxaspiro[3.4]octan-8-yl]pyrimidin-2-one；4-amino-1-[(4S,5R,6R,8R)-5-hydroxy-6-(hydroxymethyl)-1,7-dioxaspiro[3.4]octan-8-yl]pyrimidin-2-one
• CAS: 1378911-71-7
• 化学式: C₁₁H₁₅N₃O₅
• 分子量: 269.257
• InChiKey: IAWVRYQPXVENTD-AAQQEJRNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.1
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  118
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-amino-1-((4S,5R,7R,8R)-8-hydroxy-7-(hydroxymethyl)-1,6-dioxaspiro[3.4]octan-5-yl)pyrimidin-2(1H)-one 在 N,N-二甲基丙烯基脲 、 三正丁胺 、 三丁基焦磷酸铵 、 三氯氧磷 作用下， 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
• 作为产物：
  描述：

  1-[2-O,2-C-ethano-3,5-di-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-β-D-arabinofuranosyl]uracil 在 吡啶 、 4-二甲氨基吡啶 、 四丁基氟化铵 、 氨 、 三乙胺 、 对甲苯磺酰氯 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 25.0h， 生成 4-amino-1-((4S,5R,7R,8R)-8-hydroxy-7-(hydroxymethyl)-1,6-dioxaspiro[3.4]octan-5-yl)pyrimidin-2(1H)-one
  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：EP3042910A2

  公开（公告）日：2016-07-13

  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, wherein B is selected from among B2 and B3 represented by the following structures:

  本文公开了式 I 的 2'-spiro-nucleosides 及其衍生物，可用于治疗丙型肝炎病毒或登革热病毒感染者、 其中 B 选自以下结构代表的 B2 和 B3：
• 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