(-)-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。
• Synthesis and anti-HIV activities of symmetrical dicarboxylate esters of dinucleoside reverse transcriptase inhibitors
  作者：Hitesh K. Agarwal、Karen W. Buckheit、Robert W. Buckheit、Keykavous Parang

  DOI：10.1016/j.bmcl.2012.07.037

  日期：2012.9

  Three nucleoside analogues, 3′-fluoro-2′,3′-dideoxythymidine (FLT), 3′-azido-2′,3′-dideoxythymidine (AZT), and 2′,3′-dideoxy-3′-thiacytidine (3TC) were conjugated with three different dicarboxylic acids to afford the long chain dicarboxylate esters of nucleosides. In general, dinucleoside ester conjugates of FLT and 3TC with long chain dicarboxylic acids exhibited higher anti-HIV activity than their parent

  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。
• Synthesis and Biological Evaluation of Fatty Acyl Ester Derivatives of (−)-2′,3′-Dideoxy-3′-thiacytidine
  作者：Hitesh K. Agarwal、Bhupender S. Chhikara、Michael J. Hanley、Guofeng Ye、Gustavo F. Doncel、Keykavous Parang

  DOI：10.1021/jm300492q

  日期：2012.5.24

  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.