(E)-5-(2-bromovinyl)-2'-deoxyuridine-5'-[phenyl-(benzoxy-α,α-dimethylglycinyl)]-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: (E)-5-(2-bromovinyl)-2'-deoxyuridine-5'-[phenyl-(benzoxy-α,α-dimethylglycinyl)]-phosphate
• 英文别名: benzyl 2-[[[(2R,3S,5R)-5-[5-[(E)-2-bromoethenyl]-2,4-dioxopyrimidin-1-yl]-3-hydroxyoxolan-2-yl]methoxy-phenoxyphosphoryl]amino]-2-methylpropanoate
• 化学式: C₂₈H₃₁BrN₃O₉P
• 分子量: 664.447
• InChiKey: IZABVSHSZYBFQC-HZNPUCJOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  42
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  153
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  二氯磷酸苯酯 在 N-甲基咪唑 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 (E)-5-(2-bromovinyl)-2'-deoxyuridine-5'-[phenyl-(benzoxy-α,α-dimethylglycinyl)]-phosphate
  参考文献：
  名称：

  Anti-cancer ProTides: tuning the activity of BVDU phosphoramidates related to thymectacin

  摘要：

  Based on our wide ranging knowledge of phosphoramidate ProTides as anti-viral agents we have tuned the lead anti-cancer agent thymectacin in the ester and amino acid regions and revealed a substantial enhancement in in vitro potency versus colon and prostate cancer cell lines. Twelve analogues have been reported, with yields of 29-78%. The compounds are fully characterised and data clearly reveal the presence of two phosphate diastereoisomers, as expected, in roughly equi-molar proportions. The compounds were evaluated in tissue culture versus three different tumour cell lines, using thymectacin as the control. It is notable that minor structural modification of the parent phenyl methoxyalaninyl structure of thymectacin leads to significant enhancements in potency. In particular, replacement of the methyl ester moiety in the lead by a benzyl ester gave a 175-fold boost in potency versus colon cancer HT115. This derivative emerges as a low micromolar inhibitor of HT115 cells and a new lead for further optimisation. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.02.041

文献信息

• Anti-cancer ProTides: tuning the activity of BVDU phosphoramidates related to thymectacin
  作者：Christopher McGuigan、Jean-Christophe Thiery、Felice Daverio、Wen G. Jiang、Gaynor Davies、Malcolm Mason

  DOI：10.1016/j.bmc.2005.02.041

  日期：2005.5

  Based on our wide ranging knowledge of phosphoramidate ProTides as anti-viral agents we have tuned the lead anti-cancer agent thymectacin in the ester and amino acid regions and revealed a substantial enhancement in in vitro potency versus colon and prostate cancer cell lines. Twelve analogues have been reported, with yields of 29-78%. The compounds are fully characterised and data clearly reveal the presence of two phosphate diastereoisomers, as expected, in roughly equi-molar proportions. The compounds were evaluated in tissue culture versus three different tumour cell lines, using thymectacin as the control. It is notable that minor structural modification of the parent phenyl methoxyalaninyl structure of thymectacin leads to significant enhancements in potency. In particular, replacement of the methyl ester moiety in the lead by a benzyl ester gave a 175-fold boost in potency versus colon cancer HT115. This derivative emerges as a low micromolar inhibitor of HT115 cells and a new lead for further optimisation. (c) 2005 Elsevier Ltd. All rights reserved.