5'-O-(12-thioethyldodecanoyl)-2',3'-didehydro-2',3'-dideoxythymidine | 1099829-49-8

• 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-(12-thioethyldodecanoyl)-2',3'-didehydro-2',3'-dideoxythymidine
• 英文别名: 5'-O-(13-thiapentadecanoyl)-2',3'-didehydro-2',3'-dideoxythymidine；[(2S,5R)-5-(5-methyl-2,4-dioxo-pyrimidin-1-yl)-2,5-dihydrofuran-2-yl]methyl 12-ethylsulfanyldodecanoate；[(2S,5R)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)-2,5-dihydrofuran-2-yl]methyl 12-ethylsulfanyldodecanoate
• CAS: 1099829-49-8
• 化学式: C₂₄H₃₈N₂O₅S
• 分子量: 466.642
• InChiKey: ODYCTCCVMSDWFE-LEWJYISDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  32
• 可旋转键数：
  17
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  110
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  12-thioethyldodecanoic acid 在 4-二甲氨基吡啶 、 草酰氯 作用下， 以 苯 为溶剂， 反应 6.0h， 生成 5'-O-(12-thioethyldodecanoyl)-2',3'-didehydro-2',3'-dideoxythymidine
  参考文献：
  名称：

  Synthesis and biological evaluation of fatty acyl ester derivatives of 2′,3′-didehydro-2′,3′-dideoxythymidine

  摘要：

  A number of 5'-O-fatty acyl derivatives of 2',3'-didehydro-2',3'-dideoxythymidine (stavudine, d4T) were synthesized and evaluated for anti-HIV activities against cell-free and cell-associated virus, cellular cytotoxicity, and cellular uptake studies. The conjugates were found to be more potent than d4T. Among these conjugates, 5'-O-12-azidododecanoyl derivative of d4T (2), displaying EC50 = 3.1-22.4 mu M, showed 4- to 9-fold higher activities than d4T against cell-free and cell-associated virus. Cellular uptake studies were conducted on CCRF-CEM cell line using 5(6)-carboxyfluorescein derivatives of d4T attached through beta-alanine (9) or 12-aminododecanoic acid (10) as linkers. The fluorescein-substituted analog of d4T with long chain length (10) showed 12- to 15-fold higher cellular uptake profile than the corresponding analog with short chain length (9). These studies reveal that conjugation of fatty acids to d4T enhances the cellular uptake and anti-HIV activity of stavudine. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.02.070

文献信息

• Synthesis and biological evaluation of fatty acyl ester derivatives of 2′,3′-didehydro-2′,3′-dideoxythymidine
  作者：Hitesh K. Agarwal、Kelly Loethan、Deendayal Mandal、Gustavo F. Doncel、Keykavous Parang

  DOI：10.1016/j.bmcl.2011.02.070

  日期：2011.4

  A number of 5'-O-fatty acyl derivatives of 2',3'-didehydro-2',3'-dideoxythymidine (stavudine, d4T) were synthesized and evaluated for anti-HIV activities against cell-free and cell-associated virus, cellular cytotoxicity, and cellular uptake studies. The conjugates were found to be more potent than d4T. Among these conjugates, 5'-O-12-azidododecanoyl derivative of d4T (2), displaying EC50 = 3.1-22.4 mu M, showed 4- to 9-fold higher activities than d4T against cell-free and cell-associated virus. Cellular uptake studies were conducted on CCRF-CEM cell line using 5(6)-carboxyfluorescein derivatives of d4T attached through beta-alanine (9) or 12-aminododecanoic acid (10) as linkers. The fluorescein-substituted analog of d4T with long chain length (10) showed 12- to 15-fold higher cellular uptake profile than the corresponding analog with short chain length (9). These studies reveal that conjugation of fatty acids to d4T enhances the cellular uptake and anti-HIV activity of stavudine. (C) 2011 Elsevier Ltd. All rights reserved.