N-(methoxy-4-aminobutyryl)-O-(S-pivaloyl-2-thioethyl)-3'-azido-3'-deoxythymidin-5'-yl phosphate

• 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: N-(methoxy-4-aminobutyryl)-O-(S-pivaloyl-2-thioethyl)-3'-azido-3'-deoxythymidin-5'-yl phosphate
• 英文别名: methyl 4-[[[(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-[2-(2,2-dimethylpropanoylsulfanyl)ethoxy]phosphoryl]amino]butanoate
• 化学式: C₂₂H₃₅N₆O₉PS
• 分子量: 590.594
• InChiKey: VRXNUQWKYKDYLK-DFQABUJISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  39
• 可旋转键数：
  17
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  189
• 氢给体数：
  2
• 氢受体数：
  13

反应信息

• 作为产物：
  描述：

  4-氨基丁酸甲酯盐酸盐 、 3'-azido-3'-deoxythymidin-5'-yl S-pivaloyl-2-thioethyl hydrogenphosphonate 在 吡啶 、 三乙胺 作用下， 以 四氯化碳 为溶剂， 反应 3.0h， 以80%的产率得到N-(methoxy-4-aminobutyryl)-O-(S-pivaloyl-2-thioethyl)-3'-azido-3'-deoxythymidin-5'-yl phosphate
  参考文献：
  名称：

  S-Acyl-2-thioethyl Phosphoramidate Diester Derivatives as Mononucleotide Prodrugs

  摘要：

  The synthesis and in vitro anti-HIV activity of phosphoramidate diester derivatives of 3'-azido-2',3'-dideoxythymidine (AZT) bearing one S-pivaloyl-2-thioethyl (tBuSATE) group and various amino residues are reported. These compounds were obtained from an H-phosphonate strategy using an amidative oxidation step. Most of these derivatives appeared to inhibit HIV-1 replication, with EC50 values at micromolar concentration in thymidine kinase-deficient (TK-) cells, revealing a less restrictive intracellular decomposition process than previously reported for other phosphoramidate prodrugs. The proposed decomposition pathway of this new series of mixed pronucleotides may successively involve an esterase and a phosphoramidase hydrolysis.

  DOI：

  10.1021/jm0308444

文献信息

• <i>S</i>-Acyl-2-thioethyl Phosphoramidate Diester Derivatives as Mononucleotide Prodrugs
  作者：David Egron、Jean-Louis Imbach、Gilles Gosselin、Anne-Marie Aubertin、Christian Périgaud

  DOI：10.1021/jm0308444

  日期：2003.10.1

  The synthesis and in vitro anti-HIV activity of phosphoramidate diester derivatives of 3'-azido-2',3'-dideoxythymidine (AZT) bearing one S-pivaloyl-2-thioethyl (tBuSATE) group and various amino residues are reported. These compounds were obtained from an H-phosphonate strategy using an amidative oxidation step. Most of these derivatives appeared to inhibit HIV-1 replication, with EC50 values at micromolar concentration in thymidine kinase-deficient (TK-) cells, revealing a less restrictive intracellular decomposition process than previously reported for other phosphoramidate prodrugs. The proposed decomposition pathway of this new series of mixed pronucleotides may successively involve an esterase and a phosphoramidase hydrolysis.