1-{[(5S)-2-hydroxy-2-oxo-1,4,2-dioxaphosphinan-5-yl]methyl}-5-azacytosine | 941293-52-3

• 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-{[(5S)-2-hydroxy-2-oxo-1,4,2-dioxaphosphinan-5-yl]methyl}-5-azacytosine
• 英文别名: 5-aza-cyclic-cidofovir；1-{[(5S)-2-hydroxy-2-oxido-1,4,2-dioxaphosphinan-5-yl]methyl}-5-azacytosine；4-amino-1-[[(5S)-2-hydroxy-2-oxo-1,4,2λ5-dioxaphosphinan-5-yl]methyl]-1,3,5-triazin-2-one
• CAS: 941293-52-3
• 化学式: C₇H₁₁N₄O₅P
• 分子量: 262.162
• InChiKey: ZAFZQDSCZHSXRL-YFKPBYRVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.6
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  127
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-{[(5S)-2-hydroxy-2-oxo-1,4,2-dioxaphosphinan-5-yl]methyl}-5-azacytosine 、 四丁基氢氧化铵 以 甲醇 为溶剂， 反应 0.08h， 生成 4-amino-1-[[(5S)-2-oxido-2-oxo-1,4,2lambda5-dioxaphosphinan-5-yl]methyl]-1,3,5-triazin-2-one;tetrabutylazanium
  参考文献：
  名称：

  WO2007/65231

  摘要：

  公开号：
• 作为产物：
  描述：

  (S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]-5-azacytosine 在 N,N'-二环己基-4-吗啉脒 、 N,N'-二环己基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 以97%的产率得到1-{[(5S)-2-hydroxy-2-oxo-1,4,2-dioxaphosphinan-5-yl]methyl}-5-azacytosine
  参考文献：
  名称：

  WO2007/65231

  摘要：

  公开号：

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。
• N4-Acyl derivatives as lipophilic prodrugs of cidofovir and its 5-azacytosine analogue, (S)-HPMP-5-azaC: Chemistry and antiviral activity
  作者：Marcela Krečmerová、Radek Pohl、Milena Masojídková、Jan Balzarini、Robert Snoeck、Graciela Andrei

  DOI：10.1016/j.bmc.2014.03.031

  日期：2014.5

  Even number fatty acid residues-docosanoyl (behenoyl) and stearoyl were selected for introduction to the N-4-position of (S)-1-[3-hydroxy-2-(phosphonomethoxy) propyl] cytosine) (HPMPC, cidofovir), and its 5-azacytosine counterpart, (S)-1-[3-hydroxy-2-(phosphonomethoxy) propyl] cytosine) (HPMP-5-azaC) with the aim to prepare a new type of lipophilic prodrugs. The study on the influence of these modifications to the stability and biological activity of both antivirals was performed. Different reactivity of both systems towards acylation reactions was also found: the 4-NH2 group of cidofovir was more reactive compared to that of HPMP-5-azaC. In 5-azacytosine derivatives, we found mostly a destabilizing effect of the N-4-acylation but this could be compensated by a positive influence of the esterification of the phosphonate group. Chemical stability of the 5-azacytosine moiety in the HPMP series is increasing in the following order: HPMP-5-azaC < cyclic HPMP-5-azaC < HPMP-5-azaC esters. From the view of prodrug development, the best chemical stability was observed in case of the double prodrug 7: the N-4-behenoyl derivative of the hexadecyloxyethyl ester of cyclic HPMP-5-azaC. The free phosphonic acid (N-4-behenoyl-HPMPC) appeared to be a more potent and selective inhibitor of herpesvirus replication than the parent HPMPC derivative. (C) 2014 Elsevier Ltd. All rights reserved.
• Ester Prodrugs of Cyclic 1-(<i>S</i>)- [3-Hydroxy-2-(phosphonomethoxy)propyl]-5-azacytosine:  Synthesis and Antiviral Activity
  作者：Marcela Krečmerová、Antonín Holý、Radek Pohl、Milena Masojídková、Graciela Andrei、Lieve Naesens、Johan Neyts、Jan Balzarini、Erik De Clercq、Robert Snoeck

  DOI：10.1021/jm0707166

  日期：2007.11.1

  Reaction of 1-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]-5-azacytosine (1) with dicyclohexylcarbodiimide and N,N,-dicyclohexyl-4-morpholinocarboxamidine in dimethylformamide at elevated temperature afforded the corresponding cyclic phosphonate 2, that is, 1-[(5S)-2-hydroxy-2-oxido-1,4,2-dioxaphosphinan.-5-yl]methyl}-5-azacytosine. Compound 2 exerts strong in vitro activity against DNA viruses, comparable with activity of parent compound 1. Transformation of 2 to its tetrabutylammonium salt followed by reaction with alkyl or acyloxyalkyl halogenides enabled us to prepare a series of structurally diverse ester prodrugs: alkyl (octadecyl), alkenyl (erucyl), alkoxyalkyl (hexadecyloxyethyl), and acyloxyalkyl. (pivaloyloxyrrtethyl) (3-6). The introduction of an alkyl, alkoxyalkyl, or acyloxyalkyl ester group to the molecule resulted in an increase of antiviral activity; the most active compound was found to be the hexadecyloxyethyl ester a. The relative configuration of the diastereoisomer trans-6 was determined using H,H-NOESY NMR.
• Study of chemical stability of antivirally active 5-azacytosine acyclic nucleoside phosphonates using NMR spectroscopy
  作者：Martin Dračínský、Marcela Krečmerová、Antonín Holý

  DOI：10.1016/j.bmc.2008.05.058

  日期：2008.7

  Hydrolytic decomposition of four 5-azacytosine acyclic nucleoside phosphonates was studied. Products of the decomposition are carbamoylguanidine derivatives. Stability and decomposition products of HPMP-5-azaC (a 5-azacytosine derivative with strong antiviral activity) differ from the other derivatives. The reaction pathway of HPMP-5-azaC involves a formyl derivative formed by intramolecular transformylation reaction. (c) 2008 Elsevier Ltd. All rights reserved.
• AZACYTOSINE DERIVATIVES USEFUL AS ANTIVIRAL AGENTS
  申请人：K.U.Leuven Research & Development

  公开号：EP1966226A2

  公开（公告）日：2008-09-10