3-N-(6-bromohexyl)thymidine-5'-(phenylmethoxyalaninyl)phosphate | 256520-33-9

• 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: 3-N-(6-bromohexyl)thymidine-5'-(phenylmethoxyalaninyl)phosphate
• CAS: 256520-33-9
• 化学式: C₂₆H₃₇BrN₃O₉P
• 分子量: 646.472
• InChiKey: DCOUCEMELWEBJF-ZXIYVECSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.28
• 重原子数：
  40.0
• 可旋转键数：
  15.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  147.32
• 氢给体数：
  2.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  1-[(5R,6R,7R,9R)-4-氨基-6-(叔丁基-二甲基硅烷基)氧基-9-[(叔丁基-二甲基硅烷基)氧基甲基]-2,2-二氧代-1,8-二氧杂-2-硫杂螺[4.4]壬-3-烯-7-基]-5-甲基嘧啶-2,4-二酮 、 3-N-(6-bromohexyl)thymidine-5'-(phenylmethoxyalaninyl)phosphate 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 16.0h， 以50%的产率得到
  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+
• 作为产物：
  描述：

  phenyl methoxyalaninyl phosphorochloridate 在 N-甲基咪唑 、 potassium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 22.0h， 生成 3-N-(6-bromohexyl)thymidine-5'-(phenylmethoxyalaninyl)phosphate
  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+