[1-[2',5'-bis-O-(tert-butyldimethylsilyl)-3'-deoxy-β-D-ribofuranosyl]-3-N-[4-(N-methylcarbamoyl)butyl]thymine]-3'-spiro-5''-(4''-amino-1'',2''-oxathiole-2'',2''-dioxide)

• 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)-3'-deoxy-β-D-ribofuranosyl]-3-N-[4-(N-methylcarbamoyl)butyl]thymine]-3'-spiro-5''-(4''-amino-1'',2''-oxathiole-2'',2''-dioxide)
• 英文别名: [1-[2',5'-bis-O-(tert-butyldimethylsilyl)-β-D-ribofuranosyl]-3-N-[4-(N'-methylcarbamoyl)butyl]thymine]-3'-spiro-5''-(4''-amino-1'',2''-oxathiole-2'',2''-dioxide)；5-[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-2lambda6-thiaspiro[4.4]non-3-en-8-yl]-5-methyl-2,6-dioxopyrimidin-1-yl]-N-methylpentanamide；5-[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]-N-methylpentanamide
• 化学式: C₃₀H₅₄N₄O₉SSi₂
• 分子量: 703.017
• InChiKey: ASCMVAVLQNEOCG-XMQFHBISSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.44
• 重原子数：
  46
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  175
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  5-溴戊酸甲酯 在 potassium carbonate 、 甲胺 作用下， 以 乙醇 、 丙酮 为溶剂， 反应 8.0h， 生成 [1-[2',5'-bis-O-(tert-butyldimethylsilyl)-3'-deoxy-β-D-ribofuranosyl]-3-N-[4-(N-methylcarbamoyl)butyl]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

文献信息

• 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
  作者：María-Cruz Bonache、Cristina Chamorro、Sonsoles Velázquez、Erik De Clercq、Jan Balzarini、Fátima Rodríguez Barrios、Federico Gago、María-José Camarasa、Ana San-Félix

  DOI：10.1021/jm050437n

  日期：2005.10.1

  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).