(Z)-1-(6-amino-9H-purin-9-yl)-2-(3,4-dimethoxy-5-oxofuran-2(5H)-ylidene)ethylphosphonic acid | 661476-24-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: (Z)-1-(6-amino-9H-purin-9-yl)-2-(3,4-dimethoxy-5-oxofuran-2(5H)-ylidene)ethylphosphonic acid
• 英文别名: [(2Z)-1-(6-aminopurin-9-yl)-2-(3,4-dimethoxy-5-oxofuran-2-ylidene)ethyl]phosphonic acid
• CAS: 661476-24-0
• 化学式: C₁₃H₁₄N₅O₇P
• 分子量: 383.257
• InChiKey: IGTWFGMVQLBBQY-UTCJRWHESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.7
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  172
• 氢给体数：
  3
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  (Z)-1-(6-amino-9H-purin-9-yl)-2-(3,4-dimethoxy-5-oxofuran-2(5H)-ylidene)ethylphosphonic acid 在 5-phosphoribosyl 1-pyrophosphate synthetase 、 5-phosphoribosyl 1-pyrophosphate 作用下， 反应 6.0h， 以47%的产率得到
  参考文献：
  名称：

  Design, synthesis, and anticancer activity of phosphonic acid diphosphate derivative of adenine-containing butenolide and its water-soluble derivatives of paclitaxel with high antitumor activity

  摘要：

  Synthesis of adenine derivative of triphosphono-gamma-(Z)-ethylidene-2,3-dimethoxybutenolide 4 was accomplished by treatment of phosphonate 3 with 5-phosphoribosyl I-pyrophosphate in the presence of 5-phosphoribosyl I-pyrophosphate synthetase. It was found that triphosphonate 4 functions as an irreversible stoichiometric inactivator of the Escherichia coli ribonucleoside diphosphate reductase (RDPR). Triphosphonate 4 exhibited potent inhibitory activity against murine leukemias (L1210 and P388), breast carcinoma (MCF7), and human T-lymphoblasts (Molt4/C8 and CEM/0) cell lines. Paclitaxel ester derivatives of adenine-containing triphosphono-gamma-(Z)-ethylidene-2,3-dimethoxybutenolide 8-10 were also synthesized. Like triphosphonate 4, compound 8 exhibited inhibitory property toward RDPR. It also induced microtubule assembly similar to paclitaxel (5). The structure of the chlorodiester linker in 8 was found to account for this dual property. After treatment of MCF7 cells with compounds 4, 5, and 8, fluorescence microscope examination demonstrated the presence of nucleus shrinkage or segmentation. Bifunctional prodrug 8 exhibited higher lipophilicity than 4 and higher water-solubility than 5. Pro-dual-drug 8 exhibited more pronounced anticancer activity relative to that of the triphosphonate 4 and paclitaxel (5). In contrast, compound 9, resulting from the linkage of triphosphonate 4 and paclitaxel (5) through a diester unit, was only found to function as a highly water-soluble prodrug for paclitaxel (5). It induced microtubule assembly in vitro, but did not show inhibitory property toward RDPR. On the other hand, compound 10, an aggregate of triphosphonate 4 and paclitaxel (5), neither functioned as an inhibitor of RDPR nor exhibited microtubule assembly stimulating activity in vitro. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00524-8
• 作为产物：
  描述：

  (Z)-dimethyl 1-(6-chloro-9H-purin-9-yl)-2-(3,4-dimethoxy-5-oxofuran-2(5H)-ylidene)ethylphosphonate 在 ammonium hydroxide 、 三甲基溴硅烷 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 13.0h， 生成 (Z)-1-(6-amino-9H-purin-9-yl)-2-(3,4-dimethoxy-5-oxofuran-2(5H)-ylidene)ethylphosphonic acid
  参考文献：
  名称：

  Design, synthesis, and anticancer activity of phosphonic acid diphosphate derivative of adenine-containing butenolide and its water-soluble derivatives of paclitaxel with high antitumor activity

  摘要：

  Synthesis of adenine derivative of triphosphono-gamma-(Z)-ethylidene-2,3-dimethoxybutenolide 4 was accomplished by treatment of phosphonate 3 with 5-phosphoribosyl I-pyrophosphate in the presence of 5-phosphoribosyl I-pyrophosphate synthetase. It was found that triphosphonate 4 functions as an irreversible stoichiometric inactivator of the Escherichia coli ribonucleoside diphosphate reductase (RDPR). Triphosphonate 4 exhibited potent inhibitory activity against murine leukemias (L1210 and P388), breast carcinoma (MCF7), and human T-lymphoblasts (Molt4/C8 and CEM/0) cell lines. Paclitaxel ester derivatives of adenine-containing triphosphono-gamma-(Z)-ethylidene-2,3-dimethoxybutenolide 8-10 were also synthesized. Like triphosphonate 4, compound 8 exhibited inhibitory property toward RDPR. It also induced microtubule assembly similar to paclitaxel (5). The structure of the chlorodiester linker in 8 was found to account for this dual property. After treatment of MCF7 cells with compounds 4, 5, and 8, fluorescence microscope examination demonstrated the presence of nucleus shrinkage or segmentation. Bifunctional prodrug 8 exhibited higher lipophilicity than 4 and higher water-solubility than 5. Pro-dual-drug 8 exhibited more pronounced anticancer activity relative to that of the triphosphonate 4 and paclitaxel (5). In contrast, compound 9, resulting from the linkage of triphosphonate 4 and paclitaxel (5) through a diester unit, was only found to function as a highly water-soluble prodrug for paclitaxel (5). It induced microtubule assembly in vitro, but did not show inhibitory property toward RDPR. On the other hand, compound 10, an aggregate of triphosphonate 4 and paclitaxel (5), neither functioned as an inhibitor of RDPR nor exhibited microtubule assembly stimulating activity in vitro. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00524-8