1-[3-C-ethynyl-2,3-O-(3-nitrobenzylidene)-β-D-ribo-pentofuranosyl]cytosine | 616239-63-5

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物
• 英文名称: 1-[3-C-ethynyl-2,3-O-(3-nitrobenzylidene)-β-D-ribo-pentofuranosyl]cytosine
• CAS: 616239-63-5
• 化学式: C₁₈H₁₆N₄O₇
• 分子量: 400.348
• InChiKey: UBMDRGIBMXMANT-JLPXDJIOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.11
• 重原子数：
  29.0
• 可旋转键数：
  4.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  151.97
• 氢给体数：
  2.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  1-[3-C-ethynyl-2,3-O-(3-nitrobenzylidene)-β-D-ribo-pentofuranosyl]cytosine 在 还原型辅酶II(NADPH)四钠盐 rat liver S-9 、 potassium chloride 、 magnesium chloride 作用下， 以 水 为溶剂， 反应 3.0h， 以29%的产率得到1-[3-C-ethynyl-2,3-O-(3-aminobenzylidene)-β-D-ribo-pentofuranosyl]cytosine
  参考文献：
  名称：

  Synthesis of the cyclic and acyclic acetal derivatives of 1-(3-C-Ethynyl-β-d-ribo-pentofuranosyl)cytosine, a potent antitumor nucleoside. Design of prodrugs to be selectively activated in tumor tissues via the bio-Reduction–Hydrolysis mechanism☆

  摘要：

  We have designed and synthesized the acetal derivatives of 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)cytosine (ECyd, 1), the 2',3'-O-nitrobenzylidene derivatives 2 and 3 and the 5'-O-(alkoxy)(nitrophenyl)methyl derivatives 6-10 as potential prodrugs of ECyd. These prodrugs can be selectively activated in tumor tissues via a bio-reduction hydrolysis mechanism owing to the characteristic properties of tumor tissues, such as hypoxia and lower pH. Although the 2',3'-O-(4-nitrobenzylidene) derivatives 2 and 3 were converted bio-reductively into the corresponding 4-aminobenzylidene derivatives by rat S-9 mix, the reduction products, that is, the corresponding amino congeners 4 and 5, proved to be rather stable in an aqueous solution at pH 6.5 used as a pH model for acidic tumor tissues. In contrast, the 5'-O-(alkoxy)(4-nitropheny)methyl derivatives 6-8 were also reduced by rat S-9 mix to the corresponding amino congeners 11-13, which were hydrolyzed to release ECyd more effectively at pH 6.5 than at pH 7.4. Accordingly, the acyclic acetals 6-8 may be efficient prodrugs of ECyd, that are effectively reduced under physiological conditions releasing ECyd in acidic tumor tissues. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00104-4
• 作为产物：
  描述：

  乙炔基胞苷 在 4-二甲氨基吡啶 、 高氯酸 、 硫酸 、 sodium methylate 、 三乙胺 、 三氟乙酸 作用下， 以 甲醇 、 水 、 丙酮 、 甲苯 、 乙腈 为溶剂， 反应 11.17h， 生成 1-[3-C-ethynyl-2,3-O-(3-nitrobenzylidene)-β-D-ribo-pentofuranosyl]cytosine
  参考文献：
  名称：

  Synthesis of the cyclic and acyclic acetal derivatives of 1-(3-C-Ethynyl-β-d-ribo-pentofuranosyl)cytosine, a potent antitumor nucleoside. Design of prodrugs to be selectively activated in tumor tissues via the bio-Reduction–Hydrolysis mechanism☆

  摘要：

  We have designed and synthesized the acetal derivatives of 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)cytosine (ECyd, 1), the 2',3'-O-nitrobenzylidene derivatives 2 and 3 and the 5'-O-(alkoxy)(nitrophenyl)methyl derivatives 6-10 as potential prodrugs of ECyd. These prodrugs can be selectively activated in tumor tissues via a bio-reduction hydrolysis mechanism owing to the characteristic properties of tumor tissues, such as hypoxia and lower pH. Although the 2',3'-O-(4-nitrobenzylidene) derivatives 2 and 3 were converted bio-reductively into the corresponding 4-aminobenzylidene derivatives by rat S-9 mix, the reduction products, that is, the corresponding amino congeners 4 and 5, proved to be rather stable in an aqueous solution at pH 6.5 used as a pH model for acidic tumor tissues. In contrast, the 5'-O-(alkoxy)(4-nitropheny)methyl derivatives 6-8 were also reduced by rat S-9 mix to the corresponding amino congeners 11-13, which were hydrolyzed to release ECyd more effectively at pH 6.5 than at pH 7.4. Accordingly, the acyclic acetals 6-8 may be efficient prodrugs of ECyd, that are effectively reduced under physiological conditions releasing ECyd in acidic tumor tissues. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00104-4