(-)-5'-O-(t-butyldimethylsilyl)-2',3'-dideoxy-3'-thiacytidine | 956896-97-2

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核苷和核苷酸类似物
• 英文名称: (-)-5'-O-(t-butyldimethylsilyl)-2',3'-dideoxy-3'-thiacytidine
• 英文别名: 4-amino-1-((2R,5S)-2-(((tert-butyldimethylsilyl)oxy)methyl)-1,3-oxathiolan-5-yl)pyrimidin-2(1H)-one；4-amino-1-[(2R,5S)-2-[[tert-butyl(dimethyl)silyl]oxymethyl]-1,3-oxathiolan-5-yl]pyrimidin-2-one
• CAS: 956896-97-2
• 化学式: C₁₄H₂₅N₃O₃SSi
• 分子量: 343.522
• InChiKey: UFUWZYRJENPRFN-NWDGAFQWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.44
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  102
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (-)-5'-O-(t-butyldimethylsilyl)-2',3'-dideoxy-3'-thiacytidine 在 吡啶 、 四丁基氟化铵 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 溶剂黄146 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.5h， 生成 (-)-5'-O-(12-azidododecanoyl)-2',3'-dideoxy-3'-thiacytidine
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Fatty Acyl Ester Derivatives of (−)-2′,3′-Dideoxy-3′-thiacytidine

  摘要：

  A number of fatty acyl derivatives of (-)-2',3'-dideoxy-3'-thiacytidine (lamivudine, 3TC, 1) were synthesized and evaluated for their anti-HIV activity. The monosubstituted 5'-O-fatty acyl derivatives of 3TC (EC50 = 0.2-2.3 mu M) were more potent than the corresponding monosubstituted N-4-fatty acyl (EC50 = 0.4-29.4 mu M) and 5'-O-N-4-disubstituted (EC50 = 72.6 to >154.0 mu M) derivatives of the nucleoside. 5'-O-Myristoyl (16) and 5'-O-12-azidododecanoyl derivatives (17) were found to be the most potent compounds (EC50 = 0.2-0.9 mu M) exhibiting at least 16-36-fold higher anti-HIV activity against cell-free virus than 1 (EC50 = 11.4-32.7 mu M). The EC90 values for 16 against B-subtype and C-subtype clinical isolates were several folds lower than those of 1. The cellular uptake studies confirmed that compound 16 accumulated intracellularly after 1 h of incubation with CCRF-CEM cells and underwent intracellular hydrolysis. 5'-O-Fatty acyl derivatives of 1 showed significantly higher anti-HIV activity than the corresponding physical mixtures against the B-subtype virus.

  DOI：

  10.1021/jm300492q
• 作为产物：
  描述：

  叔丁基二甲基氯硅烷 、 拉米夫定 在 咪唑 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (-)-5'-O-(t-butyldimethylsilyl)-2',3'-dideoxy-3'-thiacytidine
  参考文献：
  名称：

  双核苷逆转录酶抑制剂的对称二羧酸酯的合成及其抗HIV活性

  摘要：

  三种核苷类似物3'-氟-2'，3'-二脱氧胸苷（FLT），3'-叠氮基2'，3'-二脱氧胸苷（AZT）和2'，3'-二脱氧胸苷3'-硫代胞苷（将3TC）与三种不同的二羧酸缀合以提供核苷的长链二羧酸酯。通常，FLT和3TC与长链二元羧酸的二核苷酯共轭物显示出比其母体核苷更高的抗HIV活性。发现FLT的十二烷酸酯和十四烷酸酯二核苷酯衍生物是针对HIV-1 US / 92/727和HIV-1 IIIB细胞的EC 50值分别为0.8-1.0 nM和3-4 nM的最有效化合物。含有长链二羧酸二酯的3TC偶联物的抗HIV活性（EC 50 = 3-60 nM）与3TC（EC 50  = 90-200 nM）相比提高了1.5-66倍。这项研究表明，二羧酸与许多核苷的对称酯缀合可产生具有改进的抗HIV谱的缀合物。

  DOI：

  10.1016/j.bmcl.2012.07.037

文献信息

• Design, Synthesis, Antiviral Activity, and Pre-Formulation Development of Poly-<i>L</i>-Arginine-Fatty Acyl Derivatives of Nucleoside Reverse Transcriptase Inhibitors
  作者：Bhanu P. Pemmaraju、Swapnil Malekar、Hitesh K. Agarwal、Rakesh K. Tiwari、Donghoon Oh、Gustavo F. Doncel、David R. Worthen、Keykavous Parang

  DOI：10.1080/15257770.2014.945649

  日期：2015.1.2

  (2015). Design, Synthesis, Antiviral Activity, and Pre-Formulation Development of Poly-L-Arginine-Fatty Acyl Derivatives of Nucleoside Reverse Transcriptase Inhibitors. Nucleosides, Nucleotides & Nucleic Acids: Vol. 34, No. 1, pp. 1-15.

  （2015）。核苷逆转录酶抑制剂的聚-L-精氨酸脂肪酸衍生物的设计，合成，抗病毒活性和预配制开发。核苷，核苷酸和核酸：第1卷。34，第1号，第1-15页。
• Compositions and methods for the delivery of therapeutics
  申请人：Board of Regents of the University of Nebraska

  公开号：US11311545B2

  公开（公告）日：2022-04-26

  The present invention provides compositions and methods for the delivery of antivirals to a cell or subject.

  本发明提供了将抗病毒药物传递到细胞或对象的组合物和方法。