[1-[2',5'-bis-O-(tert-butyldimethylsilyl)-β-D-ribofuranosyl]-3-N-(4-hydroxy-2-butenyl)thymine]-3'-spiro-5''-(4''-amino-1'',2''-oxathiole-2'',2''-dioxide) | 866855-46-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: [1-[2',5'-bis-O-(tert-butyldimethylsilyl)-β-D-ribofuranosyl]-3-N-(4-hydroxy-2-butenyl)thymine]-3'-spiro-5''-(4''-amino-1'',2''-oxathiole-2'',2''-dioxide)
• CAS: 866855-46-1
• 化学式: C₂₈H₄₉N₃O₉SSi₂
• 分子量: 659.949
• InChiKey: SDLZRRXNEHXNJD-YEPCPMPXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.08
• 重原子数：
  43.0
• 可旋转键数：
  9.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  161.31
• 氢给体数：
  2.0
• 氢受体数：
  12.0

反应信息

• 作为反应物：
  描述：

  [1-[2',5'-bis-O-(tert-butyldimethylsilyl)-β-D-ribofuranosyl]-3-N-(4-hydroxy-2-butenyl)thymine]-3'-spiro-5''-(4''-amino-1'',2''-oxathiole-2'',2''-dioxide) 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 反应 0.5h， 以75%的产率得到[1-[2',5'-bis-O-(tert-butyldimethylsilyl)-β-D-ribofuranosyl]-3-N-(4-hydroxybutyl)thymine]-3'-spiro-5''-(4''-amino-1'',2''-oxathiole-2'',2''-dioxide)
  参考文献：
  名称：

  Improving the Antiviral Efficacy and Selectivity of HIV-1 Reverse Transcriptase Inhibitor TSAO-T by the Introduction of Functional Groups at the N-3 Position

  摘要：

  Novel derivatives of the anti-HIV-1 agent, TSAO-T, bearing at the N-3 position a variety of polar, lipophilic, or aromatic groups linked to that position through flexible polymethylene linkers of different length, were prepared and evaluated for their anti-HIV activity. Several compounds (within the series of polar bearing groups) exhibited a 2-6-fold improved antiviral potency with regard to the lead compound, TSAO-T. Moreover, some of the most active N-3 TSAO derivatives retain antiviral activity against the TSAO-T-resistant HIV-1 strain (Glu138 -> Lys). Interestingly, the N-methylcarboxamide derivative 17 was 5- to 6-fold more active (IC50: 0.56 mu M) against recombinant HIV-1 reverse transcriptase than the lead compound, thus becoming the most active TSAO derivative synthesized so far. On the other hand, the N-3 methylcarboxamide TSAO derivative 12 turned out to have the highest selectivity index yet reported for this class of compounds (around >= 12 000).

  DOI：

  10.1021/jm050437n
• 作为产物：
  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 在 二异丁基氢化铝 、 potassium carbonate 作用下， 以 四氢呋喃 、 丙酮 为溶剂， 反应 4.0h， 生成 [1-[2',5'-bis-O-(tert-butyldimethylsilyl)-β-D-ribofuranosyl]-3-N-(4-hydroxy-2-butenyl)thymine]-3'-spiro-5''-(4''-amino-1'',2''-oxathiole-2'',2''-dioxide)
  参考文献：
  名称：

  Improving the Antiviral Efficacy and Selectivity of HIV-1 Reverse Transcriptase Inhibitor TSAO-T by the Introduction of Functional Groups at the N-3 Position

  摘要：

  Novel derivatives of the anti-HIV-1 agent, TSAO-T, bearing at the N-3 position a variety of polar, lipophilic, or aromatic groups linked to that position through flexible polymethylene linkers of different length, were prepared and evaluated for their anti-HIV activity. Several compounds (within the series of polar bearing groups) exhibited a 2-6-fold improved antiviral potency with regard to the lead compound, TSAO-T. Moreover, some of the most active N-3 TSAO derivatives retain antiviral activity against the TSAO-T-resistant HIV-1 strain (Glu138 -> Lys). Interestingly, the N-methylcarboxamide derivative 17 was 5- to 6-fold more active (IC50: 0.56 mu M) against recombinant HIV-1 reverse transcriptase than the lead compound, thus becoming the most active TSAO derivative synthesized so far. On the other hand, the N-3 methylcarboxamide TSAO derivative 12 turned out to have the highest selectivity index yet reported for this class of compounds (around >= 12 000).

  DOI：

  10.1021/jm050437n