[1-[2',5'-bis-O-(tert-butyldimethylsilyl)-β-D-ribofuranosyl]-3-N-[(2'''',3''''-didehydro-2'''',3''''-dideoxythymidin-3'''-yl)propyl]thymine]-3'-spiro-5''-(4''-amino-1'',2''-oxathiole 2'',2''-dioxide)

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核苷和核苷酸类似物
• 英文名称: [1-[2',5'-bis-O-(tert-butyldimethylsilyl)-β-D-ribofuranosyl]-3-N-[(2'''',3''''-didehydro-2'''',3''''-dideoxythymidin-3'''-yl)propyl]thymine]-3'-spiro-5''-(4''-amino-1'',2''-oxathiole 2'',2''-dioxide)
• 英文别名: 3-[3-[3-[(1R,3R,4R,5R)-6-amino-4-[tert-butyl(dimethyl)silyl]oxy-1-[[tert-butyl(dimethyl)silyl]oxymethyl]-8,8-dioxo-2,9-dioxa-8$l^{6}-thiaspiro[4.4]non-6-en-3-yl]-5-methyl-2,6-dioxo-pyrimidin-1-yl]propyl]-1-[(2R,5S)-5-(hydroxymethyl)-2,5-dihydrofuran-2-yl]-5-methyl-pyrimidine-2,4-dione；3-[3-[3-[(5R,6R,8R,9R)-4-amino-9-[tert-butyl(dimethyl)silyl]oxy-6-[[tert-butyl(dimethyl)silyl]oxymethyl]-2,2-dioxo-1,7-dioxa-2λ6-thiaspiro[4.4]non-3-en-8-yl]-5-methyl-2,6-dioxopyrimidin-1-yl]propyl]-1-[(2R,5S)-5-(hydroxymethyl)-2,5-dihydrofuran-2-yl]-5-methylpyrimidine-2,4-dione
• 化学式: C₃₇H₅₉N₅O₁₂SSi₂
• 分子量: 854.139
• InChiKey: KIKFZXLPQUHFDS-CDTRDKFKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.69
• 重原子数：
  57
• 可旋转键数：
  14
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  216
• 氢给体数：
  2
• 氢受体数：
  13

反应信息

• 作为产物：
  描述：

  司他夫定 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 丙酮 、 乙腈 为溶剂， 反应 21.0h， 生成 [1-[2',5'-bis-O-(tert-butyldimethylsilyl)-β-D-ribofuranosyl]-3-N-[(2'''',3''''-didehydro-2'''',3''''-dideoxythymidin-3'''-yl)propyl]thymine]-3'-spiro-5''-(4''-amino-1'',2''-oxathiole 2'',2''-dioxide)
  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.