9-[[(2S,5S)-2-(2-octadecoxyethoxy)-2-oxo-1,4,2lambda5-dioxaphosphinan-5-yl]methyl]purine-2,6-diamine | 1245542-21-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 9-[[(2S,5S)-2-(2-octadecoxyethoxy)-2-oxo-1,4,2lambda5-dioxaphosphinan-5-yl]methyl]purine-2,6-diamine
• 英文别名: 9-[[(2S,5S)-2-(2-octadecoxyethoxy)-2-oxo-1,4,2λ5-dioxaphosphinan-5-yl]methyl]purine-2,6-diamine
• CAS: 1245542-21-5
• 化学式: C₂₉H₅₃N₆O₅P
• 分子量: 596.751
• InChiKey: RUOVJFVKCPQOBR-DECSIMMDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7
• 重原子数：
  41
• 可旋转键数：
  23
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  150
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  9-{[(5S)-2-hydroxy-2-oxido-1,4,2-dioxaphosphinan-5-yl]-methyl}-2,6-diaminopurine 、 1- bromo-2-octadecyloxyethane 在 四丁基氢氧化铵 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.17h， 以34%的产率得到9-[[(2R,5S)-2-(2-octadecoxyethoxy)-2-oxo-1,4,2lambda5-dioxaphosphinan-5-yl]methyl]purine-2,6-diamine
  参考文献：
  名称：

  Synthesis of Ester Prodrugs of 9-(S)-[3-Hydroxy-2-(phosphonomethoxy)propyl]-2,6-diaminopurine (HPMPDAP) as Anti-Poxvirus Agents

  摘要：

  9-(S)-3-Hydroxy-2-(phosphonomethoxy)propyl]-2,6-diaminopurine (HPMPDAP) and its cyclic form were selected for further evaluation as potential drug candidates against poxvirus infections. To increase bioavailability of these compounds, synthesis of their structurally diverse ester prodrugs was carried out: alkoxyalkyl (hexadecyloxypropyl, octadecyloxyethyl, hexadecyloxyethyl), pivaloyloxymethyl (POM), 2,2,2-trifluoroethyl, butylsalicylyl, and prodrugs based on peptidomimetics. Most HPMPDAP prodrugs were synthesized in the form of monoesters is well as the corresponding cyclic phosphonate esters. The activity was evaluated not only against vaccinia virus hut also against different herpes viruses. The most potent and active prodrugs against vaccinia virus were the alkoxyalkyl ester derivatives of HPMPDAP, with 50% effective concentrations 400-600-fold lower than those of the parent compound. Prodrugs based on peptidomimetics, the 2,2,2-trifluoroethyl, the POM, and the butylsalicylyl derivatives, were able to inhibit vaccinia virus replication at 50% effective concentrations that were equivalent or similar to 10-fold lower than those observed for the parent compounds.

  DOI：

  10.1021/jm901828c

文献信息

• Synthesis of Ester Prodrugs of 9-(<i>S</i>)-[3-Hydroxy-2-(phosphonomethoxy)propyl]-2,6-diaminopurine (HPMPDAP) as Anti-Poxvirus Agents
  作者：Marcela Krečmerová、Antonín Holý、Graciela Andrei、Karel Pomeisl、Tomáš Tichý、Petra Břehová、Milena Masojídková、Martin Dračínský、Radek Pohl、Genevieve Laflamme、Lieve Naesens、Hon Hui、Tomas Cihlar、Johan Neyts、Erik De Clercq、Jan Balzarini、Robert Snoeck

  DOI：10.1021/jm901828c

  日期：2010.10.14

  9-(S)-3-Hydroxy-2-(phosphonomethoxy)propyl]-2,6-diaminopurine (HPMPDAP) and its cyclic form were selected for further evaluation as potential drug candidates against poxvirus infections. To increase bioavailability of these compounds, synthesis of their structurally diverse ester prodrugs was carried out: alkoxyalkyl (hexadecyloxypropyl, octadecyloxyethyl, hexadecyloxyethyl), pivaloyloxymethyl (POM), 2,2,2-trifluoroethyl, butylsalicylyl, and prodrugs based on peptidomimetics. Most HPMPDAP prodrugs were synthesized in the form of monoesters is well as the corresponding cyclic phosphonate esters. The activity was evaluated not only against vaccinia virus hut also against different herpes viruses. The most potent and active prodrugs against vaccinia virus were the alkoxyalkyl ester derivatives of HPMPDAP, with 50% effective concentrations 400-600-fold lower than those of the parent compound. Prodrugs based on peptidomimetics, the 2,2,2-trifluoroethyl, the POM, and the butylsalicylyl derivatives, were able to inhibit vaccinia virus replication at 50% effective concentrations that were equivalent or similar to 10-fold lower than those observed for the parent compounds.