ethyl (2S)-2-[[[(2R,3S,4R,5R)-3,4-dihydroxy-5-(4-thiophen-2-ylpyrrolo[2,3-d]pyrimidin-7-yl)oxolan-2-yl]methoxy-phenoxyphosphoryl]amino]propanoate | 1268354-85-3

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 吡咯并嘧啶核苷和核苷酸
• 英文名称: ethyl (2S)-2-[[[(2R,3S,4R,5R)-3,4-dihydroxy-5-(4-thiophen-2-ylpyrrolo[2,3-d]pyrimidin-7-yl)oxolan-2-yl]methoxy-phenoxyphosphoryl]amino]propanoate
• CAS: 1268354-85-3
• 化学式: C₂₆H₂₉N₄O₈PS
• 分子量: 588.578
• InChiKey: VDAQNWUBPMRFAZ-RHVCYYMLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  40
• 可旋转键数：
  12
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  183
• 氢给体数：
  3
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  ethyl ((((3aR,4R,6R,6aR)-2,2-dimethyl-6-(4-(thiophen-2-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)tetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methoxy)(phenoxy)phosphoryl)-L-alaninate 在 三氟乙酸 作用下， 以 水 为溶剂， 反应 1.0h， 以47%的产率得到ethyl (2S)-2-[[[(2R,3S,4R,5R)-3,4-dihydroxy-5-(4-thiophen-2-ylpyrrolo[2,3-d]pyrimidin-7-yl)oxolan-2-yl]methoxy-phenoxyphosphoryl]amino]propanoate
  参考文献：
  名称：

  Phosphoramidate pronucleotides of cytostatic 6-aryl-7-deazapurine ribonucleosides

  摘要：

  A series of O-phenyl methyl-, ethyl- and benzylalanyl phosphoramidate pronucleotides derived from cytostatic 6-aryl-7-deazapurine ribonucleosides were prepared by the cross-coupling reactions of the 2',3'-isopropylidene protected 6-chloro-7-deazapurine ribonucleoside phosphoramidates with (het)aryl-boronic acids or -stannanes followed by deprotection. Most of the prepared prodrugs exerted in vitro cytostatic effects against both solid tumor and lymphoid cancer cells within low micromolar range of concentrations. These activities were in general weaker or comparable to the activities of the parent nucleosides. Additional testing of selected prodrugs suggests that the lack of activity improvement over parent nucleosides is not due to the lack of permeability or inefficient catabolism of alanyl-ester by intracellular hydrolases. More likely, active efflux of prodrugs may play a role in their weak cytotoxic activity. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.11.029

文献信息

• Phosphoramidate pronucleotides of cytostatic 6-aryl-7-deazapurine ribonucleosides
  作者：Pavla Perlíková、Radek Pohl、Ivan Votruba、Robert Shih、Gabriel Birkuš、Tomáš Cihlář、Michal Hocek

  DOI：10.1016/j.bmc.2010.11.029

  日期：2011.1

  A series of O-phenyl methyl-, ethyl- and benzylalanyl phosphoramidate pronucleotides derived from cytostatic 6-aryl-7-deazapurine ribonucleosides were prepared by the cross-coupling reactions of the 2',3'-isopropylidene protected 6-chloro-7-deazapurine ribonucleoside phosphoramidates with (het)aryl-boronic acids or -stannanes followed by deprotection. Most of the prepared prodrugs exerted in vitro cytostatic effects against both solid tumor and lymphoid cancer cells within low micromolar range of concentrations. These activities were in general weaker or comparable to the activities of the parent nucleosides. Additional testing of selected prodrugs suggests that the lack of activity improvement over parent nucleosides is not due to the lack of permeability or inefficient catabolism of alanyl-ester by intracellular hydrolases. More likely, active efflux of prodrugs may play a role in their weak cytotoxic activity. (C) 2010 Elsevier Ltd. All rights reserved.