FLT(Glutamyl)-AZT | 1099829-57-8

• 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: FLT(Glutamyl)-AZT
• 英文别名: O1-[[(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxo-pyrimidin-1-yl)tetrahydrofuran-2-yl]methyl] O5-[[(2R,3S,5R)-3-fluoro-5-(5-methyl-2,4-dioxo-pyrimidin-1-yl)tetrahydrofuran-2-yl]methyl] (2S)-2-acetamidopentanedioate；1-O-[[(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-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
• CAS: 1099829-57-8
• 化学式: C₂₇H₃₃FN₈O₁₁
• 分子量: 664.604
• InChiKey: NEOXVIFAJJYMKP-CSHZPLHDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  47
• 可旋转键数：
  14
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  213
• 氢给体数：
  3
• 氢受体数：
  14

反应信息

• 作为产物：
  描述：

  3’-脱氧-3-氟胸苷 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 FLT(Glutamyl)-AZT
  参考文献：
  名称：

  Substituted nucleoside derivatives with antiviral and antimicrobial properties

  摘要：

  本发明涉及脂肪酸和脂肪醇取代的核苷衍生物，以及取代多价支架（例如聚合物、肽、多羧酸取代化合物、含有多环Saligenyl基团的化合物）的核苷和核苷衍生物，这些衍生物显示出强大的抗HIV活性。此外，它们对多药耐药、R5和细胞相关病毒显示出增强的活性。其中一些还显示出对其他性传播病原体和精子的活性。本发明提供了它们的合成方法、物质组成和使用方法。重点放在它们作为局部微生物杀灭剂的应用上，用于治疗或预防性疾病传播，尤其是HIV/AIDS。

  公开号：

  US09296776B2

文献信息

• Synthesis and Anti-HIV Activities of Glutamate and Peptide Conjugates of Nucleoside Reverse Transcriptase Inhibitors
  作者：Hitesh K. Agarwal、Bhupender S. Chhikara、Megrose Quiterio、Gustavo F. Doncel、Keykavous Parang

  DOI：10.1021/jm201551m

  日期：2012.3.22

  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.
• Substituted nucleoside derivatives with antiviral and antimicrobial properties
  申请人：Doncel Gustavo F.

  公开号：US09296776B2

  公开（公告）日：2016-03-29

  The present invention relates to fatty acid and fatty alcohol substituted nucleoside derivatives and nucleoside and nucleoside derivatives substituted on multivalent scaffolds (e.g., polymers, peptides, polycarboxylic acid substituted compounds, compounds containing polycycloSaligenyl groups) that display potent anti-HIV activity. Furthermore, they show enhanced activity against multi-drug resistant, R5, and cell-associated virus. Some of them also display activity against other sexually transmitted pathogens and sperm. The present invention provides their methods of synthesis, composition of matter, and methods of use. Emphasis is placed on their application as topical microbicides to treat or prevent sexual transmission of disease, especially HIV/AIDS.

  本发明涉及脂肪酸和脂肪醇取代的核苷衍生物，以及取代多价支架（例如聚合物、肽、多羧酸取代化合物、含有多环Saligenyl基团的化合物）的核苷和核苷衍生物，这些衍生物显示出强大的抗HIV活性。此外，它们对多药耐药、R5和细胞相关病毒显示出增强的活性。其中一些还显示出对其他性传播病原体和精子的活性。本发明提供了它们的合成方法、物质组成和使用方法。重点放在它们作为局部微生物杀灭剂的应用上，用于治疗或预防性疾病传播，尤其是HIV/AIDS。