3'-azido-2',3'-dideoxy-5-[2-(methoxycarbonyl)ethyl]uridine | 279220-31-4

• 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'-azido-2',3'-dideoxy-5-[2-(methoxycarbonyl)ethyl]uridine
• 英文别名: methyl 3-[1-[(2R,4S,5S)-4-azido-5-(hydroxymethyl)tetrahydrofuran-2-yl]-2,4-dioxo-pyrimidin-5-yl]propanoate；methyl 3-[1-[(2R,4S,5S)-4-azido-5-(hydroxymethyl)oxolan-2-yl]-2,4-dioxopyrimidin-5-yl]propanoate
• CAS: 279220-31-4
• 化学式: C₁₃H₁₇N₅O₆
• 分子量: 339.308
• InChiKey: KVRUGZHZGPEWCE-IVZWLZJFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  120
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  3'-azido-2',3'-dideoxy-5-[2-(methoxycarbonyl)ethyl]uridine 在 N-甲基吗啉 、 2-氯-4,6-二甲氧基-1,3,5-三嗪 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 143.0h， 生成 3'-azido-2',3'-dideoxy-5-[N-15-[6-(3,5-dimethylphenylthio)-5-ethyl-1-(5-oxopentyl)uracil]-4,15-diaza-3-oxopentadecanyl]uridine
  参考文献：
  名称：

  Synthesis and Evaluation of “AZT-HEPT”, “AZT-Pyridinone”, and “ddC-HEPT” Conjugates as Inhibitors of HIV Reverse Transcriptase

  摘要：

  To test the concept that HIV reverse transcriptase could be effectively inhibited by "mixed site inhibitors", a series of seven conjugates containing both a nucleoside analogue component(AZT 1, ddC 2) and a nonnucleoside type inhibitor (HEPT analogue 12, pyridinone 27) were synthesized and evaluated for their ability to block HIV replication. The (N-3 and C-5)AZT-HEPT conjugates 15, 22, and 23 displayed 2-5 mu M anti-HIV activity, but they had no effect on the replication of HIV-2 or the HIV-1 strain with the Y181C mutation. The (C-5)AZT-pyridinone conjugates 34-37 were found to be inactive. In marked contrast, the ddC-HEPT molecule 26 displayed the same potency (EC50 = 0.45 mu M) against HTV-1 (wild type and the Y181C nevirapine-resistant strain) and HIV-2 in cell culture. No synergistic effect was-observed for these bis-substrate inhibitors, suggesting that the two individual inhibitor components in these molecules do not bind simultaneously in their respective sites. Interestingly, however, the results indicate that the AZT-HEPT conjugates and the ddC-HEPT derivative 26 inhibit reverse transcriptase (RT) in an opposite manner. One explanation for this difference is that the former compounds interact preferentially with the hydrophobic pocket in RT, whereas 26 (after supposed triphosphorylation) inhibits RT through binding in the catalytic site.

  DOI：

  10.1021/jm991125l
• 作为产物：
  描述：

  3'-azido-2',3'-dideoxy-5-[2-(methoxycarbonyl)ethyl]-5'-O-(4-methoxytrityl)uridine 在 Dowex 50X₂-200 mesh ion-exchange resin 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以89%的产率得到3'-azido-2',3'-dideoxy-5-[2-(methoxycarbonyl)ethyl]uridine
  参考文献：
  名称：

  Synthesis and Evaluation of “AZT-HEPT”, “AZT-Pyridinone”, and “ddC-HEPT” Conjugates as Inhibitors of HIV Reverse Transcriptase

  摘要：

  To test the concept that HIV reverse transcriptase could be effectively inhibited by "mixed site inhibitors", a series of seven conjugates containing both a nucleoside analogue component(AZT 1, ddC 2) and a nonnucleoside type inhibitor (HEPT analogue 12, pyridinone 27) were synthesized and evaluated for their ability to block HIV replication. The (N-3 and C-5)AZT-HEPT conjugates 15, 22, and 23 displayed 2-5 mu M anti-HIV activity, but they had no effect on the replication of HIV-2 or the HIV-1 strain with the Y181C mutation. The (C-5)AZT-pyridinone conjugates 34-37 were found to be inactive. In marked contrast, the ddC-HEPT molecule 26 displayed the same potency (EC50 = 0.45 mu M) against HTV-1 (wild type and the Y181C nevirapine-resistant strain) and HIV-2 in cell culture. No synergistic effect was-observed for these bis-substrate inhibitors, suggesting that the two individual inhibitor components in these molecules do not bind simultaneously in their respective sites. Interestingly, however, the results indicate that the AZT-HEPT conjugates and the ddC-HEPT derivative 26 inhibit reverse transcriptase (RT) in an opposite manner. One explanation for this difference is that the former compounds interact preferentially with the hydrophobic pocket in RT, whereas 26 (after supposed triphosphorylation) inhibits RT through binding in the catalytic site.

  DOI：

  10.1021/jm991125l