1-O-[[(2R,5S)-5-[4-[[bis(4-methoxyphenyl)-phenylmethyl]amino]-2-oxopyrimidin-1-yl]-1,3-oxathiolan-2-yl]methyl] 5-O-[[(2R,3S,5R)-3-fluoro-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl] (2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)pentanedioate | 1365246-71-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: 1-O-[[(2R,5S)-5-[4-[[bis(4-methoxyphenyl)-phenylmethyl]amino]-2-oxopyrimidin-1-yl]-1,3-oxathiolan-2-yl]methyl] 5-O-[[(2R,3S,5R)-3-fluoro-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl] (2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)pentanedioate
• CAS: 1365246-71-4
• 化学式: C₅₉H₅₇FN₆O₁₃S
• 分子量: 1109.2
• InChiKey: YGQKKTHTGDGNEU-XZOQCKBJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.5
• 重原子数：
  80
• 可旋转键数：
  23
• 环数：
  10.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  247
• 氢给体数：
  3
• 氢受体数：
  15

反应信息

• 作为反应物：
  描述：

  1-O-[[(2R,5S)-5-[4-[[bis(4-methoxyphenyl)-phenylmethyl]amino]-2-oxopyrimidin-1-yl]-1,3-oxathiolan-2-yl]methyl] 5-O-[[(2R,3S,5R)-3-fluoro-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl] (2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)pentanedioate 在 哌啶 、 1-辛硫醇 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 1-O-[[(2R,5S)-5-[4-[[bis(4-methoxyphenyl)-phenylmethyl]amino]-2-oxopyrimidin-1-yl]-1,3-oxathiolan-2-yl]methyl] 5-O-[[(2R,3S,5R)-3-fluoro-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl] (2S)-2-acetamidopentanedioate
  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：

  3’-脱氧-3-氟胸苷 在 水 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 1-O-[[(2R,5S)-5-[4-[[bis(4-methoxyphenyl)-phenylmethyl]amino]-2-oxopyrimidin-1-yl]-1,3-oxathiolan-2-yl]methyl] 5-O-[[(2R,3S,5R)-3-fluoro-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl] (2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)pentanedioate
  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