Fmoc-Glu(3'-azido-2',3'-dideoxythymidin-5'-yl)OtBu | 1365246-68-9

• 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: Fmoc-Glu(3'-azido-2',3'-dideoxythymidin-5'-yl)OtBu
• 英文别名: 5-O-[[(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl] 1-O-tert-butyl (2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)pentanedioate
• CAS: 1365246-68-9
• 化学式: C₃₄H₃₈N₆O₉
• 分子量: 674.711
• InChiKey: UUALKOZNEWXKNR-YVHASNINSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  49
• 可旋转键数：
  15
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  164
• 氢给体数：
  2
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  Fmoc-Glu(3'-azido-2',3'-dideoxythymidin-5'-yl)OtBu 在 水 、 三氟乙酸 作用下， 反应 1.0h， 以5.2 g的产率得到Fmoc-Glu(3'-azido-2',3'-dideoxythymidin-5'-yl)-OH
  参考文献：
  名称：

  Synthesis and Anti-HIV Activities of Glutamate and Peptide Conjugates of Nucleoside Reverse Transcriptase Inhibitors

  摘要：

  Mono-, di-, and trinucleoside conjugates of glutamate or peptide scaffolds containing nucleoside reverse transcriptase inhibitors were synthesized. Among dinucleoside glutamate ester derivatives, N-myristoylated derivatives showed significantly higher anti-HIV activity than the corresponding N-acetylated conjugates against cell-free virus. Myristoyl-Glu(3TC)-FLT (46, EC50 = 0.3-0.6 mu M) and myristoyl-Glu(FTC)-FLT (47, EC50 = 0.1-0.4 mu M) derivatives were the most active glutamate-dinucleoside conjugates. A trinucleoside glutamate derivative containing AZT, FLT, and 3TC (34, EC50 = 0.9-1.4 mu M) exhibited higher anti-HIV activity than AZT and 3TC against cell-free virus. Compound 34 also exhibited higher anti-HIV activity against multidrug (IC50 = 5.9 nM) and NNRTI (IC50 = 12.9 nM) resistant viruses than parent nucleosides. The physical mixture containing FLT-succinate, AZT, 3TC, and glutamic acid exhibited 115-fold less activity against cell associated virus (EC50 = 91.9 mu M) when compared to 34 (EC50 = 0.8 mu M). Other conjugates showed less or comparable potency to that of the corresponding physical mixtures.

  DOI：

  10.1021/jm201551m
• 作为产物：
  描述：

  芴甲氧羰基-L-谷氨酸 1-叔丁酯 、 齐多夫定 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 Fmoc-Glu(3'-azido-2',3'-dideoxythymidin-5'-yl)OtBu
  参考文献：
  名称：

  Synthesis and Anti-HIV Activities of Glutamate and Peptide Conjugates of Nucleoside Reverse Transcriptase Inhibitors

  摘要：

  Mono-, di-, and trinucleoside conjugates of glutamate or peptide scaffolds containing nucleoside reverse transcriptase inhibitors were synthesized. Among dinucleoside glutamate ester derivatives, N-myristoylated derivatives showed significantly higher anti-HIV activity than the corresponding N-acetylated conjugates against cell-free virus. Myristoyl-Glu(3TC)-FLT (46, EC50 = 0.3-0.6 mu M) and myristoyl-Glu(FTC)-FLT (47, EC50 = 0.1-0.4 mu M) derivatives were the most active glutamate-dinucleoside conjugates. A trinucleoside glutamate derivative containing AZT, FLT, and 3TC (34, EC50 = 0.9-1.4 mu M) exhibited higher anti-HIV activity than AZT and 3TC against cell-free virus. Compound 34 also exhibited higher anti-HIV activity against multidrug (IC50 = 5.9 nM) and NNRTI (IC50 = 12.9 nM) resistant viruses than parent nucleosides. The physical mixture containing FLT-succinate, AZT, 3TC, and glutamic acid exhibited 115-fold less activity against cell associated virus (EC50 = 91.9 mu M) when compared to 34 (EC50 = 0.8 mu M). Other conjugates showed less or comparable potency to that of the corresponding physical mixtures.

  DOI：

  10.1021/jm201551m