(-)-N(4)-(tetradecanoyl)-2',3'-dideoxy-3'-thiacytidine | 1373400-22-6

• 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: (-)-N(4)-(tetradecanoyl)-2',3'-dideoxy-3'-thiacytidine
• 英文别名: N-[1-[(2R,5S)-2-(hydroxymethyl)-1,3-oxathiolan-5-yl]-2-oxo-pyrimidin-4-yl]tetradecanamide；N-[1-[(2R,5S)-2-(hydroxymethyl)-1,3-oxathiolan-5-yl]-2-oxopyrimidin-4-yl]tetradecanamide
• CAS: 1373400-22-6
• 化学式: C₂₂H₃₇N₃O₄S
• 分子量: 439.619
• InChiKey: HHSMIDNHNUAGBT-LEWJYISDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  30
• 可旋转键数：
  15
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  117
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  拉米夫定 在 咪唑 、 4-二甲氨基吡啶 、 四丁基氟化铵 作用下， 以 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 25.0h， 生成 (-)-N(4)-(tetradecanoyl)-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

文献信息

• 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.