5'-[(2-氨基苯基)乙酰基]-2'-脱氧-5-氟尿苷 | 650629-23-5

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 中文名称: 5'-[(2-氨基苯基)乙酰基]-2'-脱氧-5-氟尿苷
• 英文名称: 5'-[(2-aminophenyl)acetyl]-2'-deoxy-5-fluorouridine
• 英文别名: [(2S,4R,5R)-5-(5-fluoro-2,4-dioxopyrimidin-1-yl)-4-hydroxyoxolan-2-yl]methyl 2-(2-aminophenyl)acetate
• CAS: 650629-23-5
• 化学式: C₁₇H₁₈FN₃O₆
• 分子量: 379.345
• InChiKey: WYLUZNXBLFJSSQ-OWRWGESLSA-N

物化性质

• 熔点：
  78-80 °C
• 密度：
  1.51±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  131
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  5'-[(2-氨基苯基)乙酰基]-2'-脱氧-5-氟尿苷 在 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 phosphate buffer 为溶剂， 反应 16.0h， 生成 5'-(3-(2-nitrophenyl)propionyl)-2'-deoxy-5-fluorouridine
  参考文献：
  名称：

  5′-(2-Nitrophenylalkanoyl)-2′-deoxy-5-fluorouridines as potential prodrugs of FUDR for reductive activation

  摘要：

  Four 5'-(2-nitrophenylalkanoyl)-2'-deoxy-5-fluorouridines (1a-d) were designed and synthesized as potential prodrugs of FUDR for reductive activation. Two methyl groups were introduced alpha to the ester carbonyl to increase both the rate of cyclization activation and the stability of the conjugates towards serum esterases. Chemical reduction of the nitro group into an amino leads to cyclization and release of the active FUDR. Kinetic analysis of the cyclization activation process indicates that the two methyl groups alpha to the ester carbonyl restrict the rotational freedom of ground state molecule and promote the cyclization reaction. However, the two methyl groups also were found to render the conjugates as poor substrates of E. coli B nitroreductase. Conjugate 1c, without the two methyl groups, was reduced by E. coli B nitroreductase (t(1/2) = 8 h) to give two products, a N-hydroxyl lactam and the drug FUDR, suggesting that the enzymatic reduction and subsequent cyclization activation proceeded through the hydroxylamine intermediate. These results indicate that cyclization activation will occur once the nitro group is reduced either to an amino or to a hydroxylamino group. The fact that the amino intermediates cyclized easily to release the incorporated drug FUDR suggests the feasibility of using peptide-linked acyl 2-aminophenylalkanoic acid esters as potential prodrugs for proteolytic activation. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00426-7
• 作为产物：
  描述：

  5'-[(2-硝基苯基)乙酰基]-2'-脱氧-5-氟尿苷 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 生成 5'-[(2-氨基苯基)乙酰基]-2'-脱氧-5-氟尿苷
  参考文献：
  名称：

  5′-(2-Nitrophenylalkanoyl)-2′-deoxy-5-fluorouridines as potential prodrugs of FUDR for reductive activation

  摘要：

  Four 5'-(2-nitrophenylalkanoyl)-2'-deoxy-5-fluorouridines (1a-d) were designed and synthesized as potential prodrugs of FUDR for reductive activation. Two methyl groups were introduced alpha to the ester carbonyl to increase both the rate of cyclization activation and the stability of the conjugates towards serum esterases. Chemical reduction of the nitro group into an amino leads to cyclization and release of the active FUDR. Kinetic analysis of the cyclization activation process indicates that the two methyl groups alpha to the ester carbonyl restrict the rotational freedom of ground state molecule and promote the cyclization reaction. However, the two methyl groups also were found to render the conjugates as poor substrates of E. coli B nitroreductase. Conjugate 1c, without the two methyl groups, was reduced by E. coli B nitroreductase (t(1/2) = 8 h) to give two products, a N-hydroxyl lactam and the drug FUDR, suggesting that the enzymatic reduction and subsequent cyclization activation proceeded through the hydroxylamine intermediate. These results indicate that cyclization activation will occur once the nitro group is reduced either to an amino or to a hydroxylamino group. The fact that the amino intermediates cyclized easily to release the incorporated drug FUDR suggests the feasibility of using peptide-linked acyl 2-aminophenylalkanoic acid esters as potential prodrugs for proteolytic activation. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00426-7