3'-azido-3'-deoxythymidin-5'-yl 2-(phenylthio)ethyl p-tolyl phosphate

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3'-azido-3'-deoxythymidin-5'-yl 2-(phenylthio)ethyl p-tolyl phosphate
• 英文别名: [(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl (4-methylphenyl) 2-phenylsulfanylethyl phosphate
• 化学式: C₂₅H₂₈N₅O₇PS
• 分子量: 573.566
• InChiKey: HIMYHRGDBWXDNB-FDXOTVGBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  39
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  143
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  3'-azido-3'-deoxythymidin-5'-yl 2-(phenylthio)ethyl p-tolyl phosphate 在 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以58%的产率得到3'-azido-3'-deoxythymidin-5'-yl 2-(phenylsulfonyl)ethyl p-tolyl phosphate
  参考文献：
  名称：

  Synthesis and evaluation of sulfonylethyl-containing phosphotriesters of 3′-azido-3′-deoxythymidine as anticancer prodrugs

  摘要：

  A series of bis(sulfonylethyl) and mono(sulfonylethyl) phenyl phosphotriesters of zidovudine (3'-azido-3'-deoxythymidine, AZT) were synthesized as potential anticancer prodrugs that liberate AZT monophosphate via nonenzymatic beta-elimination mechanism. Stability studies demonstrated that all the synthesized prodrugs spontaneously liberate AZT monophosphate with half-lives in the range of 0.07-278.8 h under model physiological conditions in 0.1 M phosphate buffer at pH 7.4 and 37 degrees C. Analogous to aldophosphamide, the elimination rates were accelerated in the presence of reconstituted human plasma under the same conditions. Among the compounds, 3, 4, 8, and 10 were comparable or superior to AZT against five established human cancerous cell lines in vitro. Moreover, the selected compounds were equally sensitive to both the wild-type osteosarcoma 143B and the thymidine kinase-deficient 143B/TK cell lines. The findings are consistent with that these compounds deliver AZT monophosphate intracellularly. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.09.046
• 作为产物：
  描述：

  2-苯硫基乙醇 在 四氮唑 、 4,5-二氰基咪唑 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙腈 为溶剂， 反应 6.0h， 生成 3'-azido-3'-deoxythymidin-5'-yl 2-(phenylthio)ethyl p-tolyl phosphate
  参考文献：
  名称：

  Synthesis and evaluation of sulfonylethyl-containing phosphotriesters of 3′-azido-3′-deoxythymidine as anticancer prodrugs

  摘要：

  A series of bis(sulfonylethyl) and mono(sulfonylethyl) phenyl phosphotriesters of zidovudine (3'-azido-3'-deoxythymidine, AZT) were synthesized as potential anticancer prodrugs that liberate AZT monophosphate via nonenzymatic beta-elimination mechanism. Stability studies demonstrated that all the synthesized prodrugs spontaneously liberate AZT monophosphate with half-lives in the range of 0.07-278.8 h under model physiological conditions in 0.1 M phosphate buffer at pH 7.4 and 37 degrees C. Analogous to aldophosphamide, the elimination rates were accelerated in the presence of reconstituted human plasma under the same conditions. Among the compounds, 3, 4, 8, and 10 were comparable or superior to AZT against five established human cancerous cell lines in vitro. Moreover, the selected compounds were equally sensitive to both the wild-type osteosarcoma 143B and the thymidine kinase-deficient 143B/TK cell lines. The findings are consistent with that these compounds deliver AZT monophosphate intracellularly. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.09.046

文献信息

• Synthesis and evaluation of sulfonylethyl-containing phosphotriesters of 3′-azido-3′-deoxythymidine as anticancer prodrugs
  作者：Jiang Wang、Yi-Jun Wang、Zhe-Sheng Chen、Chul-Hoon Kwon

  DOI：10.1016/j.bmc.2014.09.046

  日期：2014.11

  A series of bis(sulfonylethyl) and mono(sulfonylethyl) phenyl phosphotriesters of zidovudine (3'-azido-3'-deoxythymidine, AZT) were synthesized as potential anticancer prodrugs that liberate AZT monophosphate via nonenzymatic beta-elimination mechanism. Stability studies demonstrated that all the synthesized prodrugs spontaneously liberate AZT monophosphate with half-lives in the range of 0.07-278.8 h under model physiological conditions in 0.1 M phosphate buffer at pH 7.4 and 37 degrees C. Analogous to aldophosphamide, the elimination rates were accelerated in the presence of reconstituted human plasma under the same conditions. Among the compounds, 3, 4, 8, and 10 were comparable or superior to AZT against five established human cancerous cell lines in vitro. Moreover, the selected compounds were equally sensitive to both the wild-type osteosarcoma 143B and the thymidine kinase-deficient 143B/TK cell lines. The findings are consistent with that these compounds deliver AZT monophosphate intracellularly. (C) 2014 Elsevier Ltd. All rights reserved.