5'-(phenylmethoxyalaninyl)phosphate thymidine | 256520-25-9

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 5'-(phenylmethoxyalaninyl)phosphate thymidine
• 英文别名: 5'-{O-phenyl-N-[(1S)-2-oxo-2-methoxy-1-methylethyl]phosphoramidate}；methyl thymidine-5'-phenylphosphoryl-P-N-alaninate；methyl (2S)-2-[[[(2R,3S,5R)-3-hydroxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-oxido-phenoxyphosphaniumyl]amino]propanoate
• CAS: 256520-25-9
• 化学式: C₂₀H₂₆N₃O₉P
• 分子量: 483.415
• InChiKey: YXBWTQJCIYZPPG-RIDWFCTOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  33
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  159
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  5'-(phenylmethoxyalaninyl)phosphate thymidine 在 水 、 sodium chloride 作用下， 生成 胸苷酸
  参考文献：
  名称：

  胸苷5'-邻-苯基-N-烷基膦酰胺酸酯的水解反应，核苷5'-单磷酸酯前药的模型。

  摘要：

  从而导致胸腺嘧啶核苷或苯酚的离开而没有任何中间体的明显积累。两种途径都代表3总体消失的一半。苯酚的离开最终导致5'-磷酸胸苷的形成。在pH> 5时，主要反应是羧酸酯键的水解，然后是羧酸根离子在分子内置换酚盐离子，然后将所得的环状混合酸酐水解成无环二酯状胸苷5'-氨基磷酸酯。后者产物定量地积累，没有任何进一步分解的迹象。原料3的氢氧根离子催化的P-OPh键断裂是副反应。与胸苷5'的比较测量

  DOI：

  10.1002/chem.200700623
• 作为产物：
  描述：

  phenyl methoxyalaninyl phosphorochloridate 、 beta-胸苷 在 N-甲基咪唑 作用下， 以 四氢呋喃 为溶剂， 以41%的产率得到5'-(phenylmethoxyalaninyl)phosphate thymidine
  参考文献：
  名称：

  Potential Multifunctional Inhibitors of HIV-1 Reverse Transcriptase. Novel [AZT]-[TSAO-T] and [d4T]-[TSAO-T] Heterodimers Modified in the Linker and in the Dideoxynucleoside Region

  摘要：

  In an attempt to combine the anti-HIV-inhibitory capacity of nucleoside reverse transcriptase (RT) inhibitors (NRTI) and non-nucleoside RT inhibitors (NNRTI), several heterodimer analogues of the previously reported [AZT]-(CH(2))(3)-[TSAO-T] prototype have been prepared. In these novel series, other NRTIs, an expanded range of linkers with different conformational freedom and other attachment sites for these linkers on the base part of the NRTI analogue have been explored. Moreover, in order to circumvent the dependence of the NRTI moiety of the heterodimer an activation by cellular nucleoside kinases, novel heterodimers in which the NRTI is bearing a masked monophosphate group at the 5'-position are described. Among the novel heterodimers, several derivatives show a potent anti-HIV-1 activity, which proved comparable, or even superior, to that of the AZT heterodimer prototype. The nature of the NRTI was important far the eventual anti-HIV-1 activity. In particular, the d4T heterodimer derivative containing a propyl linker between the N-3 positions of the base of TSAO-T and d4T was similar to 5- to 10-fold more inhibitory to HIV-1 than the corresponding AZT heterodimer prototype.

  DOI：

  10.1021/jm991092+

文献信息

• Potential Multifunctional Inhibitors of HIV-1 Reverse Transcriptase. Novel [AZT]-[TSAO-T] and [d4T]-[TSAO-T] Heterodimers Modified in the Linker and in the Dideoxynucleoside Region
  作者：Sonsoles Velázquez、Victoria Tuñón、María Luisa Jimeno、Cristina Chamorro、Erik De Clercq、Jan Balzarini、María José Camarasa

  DOI：10.1021/jm991092+

  日期：1999.12.1

  In an attempt to combine the anti-HIV-inhibitory capacity of nucleoside reverse transcriptase (RT) inhibitors (NRTI) and non-nucleoside RT inhibitors (NNRTI), several heterodimer analogues of the previously reported [AZT]-(CH(2))(3)-[TSAO-T] prototype have been prepared. In these novel series, other NRTIs, an expanded range of linkers with different conformational freedom and other attachment sites for these linkers on the base part of the NRTI analogue have been explored. Moreover, in order to circumvent the dependence of the NRTI moiety of the heterodimer an activation by cellular nucleoside kinases, novel heterodimers in which the NRTI is bearing a masked monophosphate group at the 5'-position are described. Among the novel heterodimers, several derivatives show a potent anti-HIV-1 activity, which proved comparable, or even superior, to that of the AZT heterodimer prototype. The nature of the NRTI was important far the eventual anti-HIV-1 activity. In particular, the d4T heterodimer derivative containing a propyl linker between the N-3 positions of the base of TSAO-T and d4T was similar to 5- to 10-fold more inhibitory to HIV-1 than the corresponding AZT heterodimer prototype.
• Hydrolytic Reactions of Thymidine 5′-O-Phenyl-N-Alkylphosphoramidates, Models of Nucleoside 5′-Monophosphate Prodrugs
  作者：Mikko Ora、Jarno Ojanperä、Harri Lönnberg

  DOI：10.1002/chem.200700623

  日期：2007.10.15

  of the starting material 3 occurred as a side reaction. Comparative measurements with thymidine 5'-N-[(1S)-2-oxo-2-methoxy-1-methylethyl]phosphoramidate} (4) revealed that, under acidic conditions, this diester-like compound is hydrolyzed by P--N bond cleavage three orders of magnitude more rapidly than the triester-like 3. At pH>5, the stability order is reversed, with 3 being hydrolyzed six times

  从而导致胸腺嘧啶核苷或苯酚的离开而没有任何中间体的明显积累。两种途径都代表3总体消失的一半。苯酚的离开最终导致5'-磷酸胸苷的形成。在pH> 5时，主要反应是羧酸酯键的水解，然后是羧酸根离子在分子内置换酚盐离子，然后将所得的环状混合酸酐水解成无环二酯状胸苷5'-氨基磷酸酯。后者产物定量地积累，没有任何进一步分解的迹象。原料3的氢氧根离子催化的P-OPh键断裂是副反应。与胸苷5'的比较测量