1-[(2S)-2-(diisopropoxyphosphoryl)methoxy-3-hydroxypropyl]-6-methyl-5-azacytosine | 1207842-52-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三嗪类
• 英文名称: 1-[(2S)-2-(diisopropoxyphosphoryl)methoxy-3-hydroxypropyl]-6-methyl-5-azacytosine
• 英文别名: 4-amino-1-[(2S)-2-[di(propan-2-yloxy)phosphorylmethoxy]-3-hydroxypropyl]-6-methyl-1,3,5-triazin-2-one
• CAS: 1207842-52-1
• 化学式: C₁₄H₂₇N₄O₆P
• 分子量: 378.365
• InChiKey: HRWSWQGCYFUKBZ-LBPRGKRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  25
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  136
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-[(2S)-2-(diisopropoxyphosphoryl)methoxy-3-hydroxypropyl]-6-methyl-5-azacytosine 在 三甲基溴硅烷 、 三乙基碳酸氢铵缓冲液 、 甲酸 、 溶剂黄146 作用下， 以 乙腈 、 甲醇 、 水 为溶剂， 反应 48.0h， 生成 1-(S)-3-hydroxy-2-[(phosphonomethoxy)propyl]-6-methyl-5-azacytosine
  参考文献：
  名称：

  Acyclic nucleoside phosphonates with 5-azacytosine base moiety substituted in C-6 position

  摘要：

  Two methods for preparation of 6-substituted derivatives of anti DNA-viral agent 1-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]-5-azacytosine (HPMP-5-azaC) were developed: (1) ammonia mediated ring-opening reaction of diisopropyl esters of HPMP-5-azaC (4) to carbamoylguanidine derivatives followed by ring-closure reaction with orthoesters and (2) condensation reaction of 6-substituted 5-azacytosines with diisopropyl (1S)-[2-hydroxy-1-tosyloxymethyl)ethoxy]methylphosphonate (15). Deprotection of diisopropyl esters to free phosphonic acids was performed with bromotrimethylsilane in acetonitrile followed by hydrolysis. In contrast to parent compound HPMP-5-azaC, a substantial decrease of antiviral activity in case of 6-substituted analogues occurred. Surprisingly, N-3 isomer of 6-methyl-HPMP-5-azaC in the form of isopropyl ester revealed activity against RNA viruses (Sindbis virus). (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.10.044
• 作为产物：
  描述：

  4-氨基-6-甲基-1,3,5-三嗪-2-醇 、 (R)-2-[(diisopropoxyphosphoryl)methoxy]-3-hydroxypropyl p-toluenesulfonate 在 sodium methylate 、 caesium carbonate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以42%的产率得到3-[(2S)-2-(diisopropoxyphosphoryl)methoxy-3-hydroxypropyl]-6-methyl-5-azacytosine
  参考文献：
  名称：

  Acyclic nucleoside phosphonates with 5-azacytosine base moiety substituted in C-6 position

  摘要：

  Two methods for preparation of 6-substituted derivatives of anti DNA-viral agent 1-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]-5-azacytosine (HPMP-5-azaC) were developed: (1) ammonia mediated ring-opening reaction of diisopropyl esters of HPMP-5-azaC (4) to carbamoylguanidine derivatives followed by ring-closure reaction with orthoesters and (2) condensation reaction of 6-substituted 5-azacytosines with diisopropyl (1S)-[2-hydroxy-1-tosyloxymethyl)ethoxy]methylphosphonate (15). Deprotection of diisopropyl esters to free phosphonic acids was performed with bromotrimethylsilane in acetonitrile followed by hydrolysis. In contrast to parent compound HPMP-5-azaC, a substantial decrease of antiviral activity in case of 6-substituted analogues occurred. Surprisingly, N-3 isomer of 6-methyl-HPMP-5-azaC in the form of isopropyl ester revealed activity against RNA viruses (Sindbis virus). (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.10.044

文献信息

• Azacytosine Derivatives Useful as Antiviral Agents
  申请人：Holy Antonin

  公开号：US20090005346A1

  公开（公告）日：2009-01-01

  The present invention provides 5-azacytosine derivatives with antiviral activity, specifically having viral replication inhibiting properties, more particularly in DNA viruses such as pox-, papilloma- and herpes viruses in humans. The invention also provides pharmaceutical compositions comprising such 5-azacytosine derivatives as active ingredients in combination with pharmaceutically acceptable carriers, which are useful for the treatment of subjects suffering from viral infections.

  本发明提供了具有抗病毒活性的5-氮杂胞嘧啶衍生物，特别是具有病毒复制抑制性质，更具体地针对DNA病毒，例如人类痘病毒、乳头瘤病毒和疱疹病毒。本发明还提供了药物组合物，其中包括这种5-氮杂胞嘧啶衍生物作为活性成分与药用载体结合，可用于治疗患有病毒感染的个体。
• US8153787B2
  申请人：——

  公开号：US8153787B2

  公开（公告）日：2012-04-10