N-(3,4,6-tri-O-acetyl-2-fluoro-2-deoxy-β-D-glucopyranosyl)-4-(N'-benzyloxycarbonyl-N'-methylamino)butanamide | 1313587-81-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(3,4,6-tri-O-acetyl-2-fluoro-2-deoxy-β-D-glucopyranosyl)-4-(N'-benzyloxycarbonyl-N'-methylamino)butanamide
• 英文别名: [(2R,3R,4S,5R,6R)-3,4-diacetyloxy-5-fluoro-6-[4-[methyl(phenylmethoxycarbonyl)amino]butanoylamino]oxan-2-yl]methyl acetate
• CAS: 1313587-81-3
• 化学式: C₂₅H₃₃FN₂O₁₀
• 分子量: 540.543
• InChiKey: KJIZQWKEDNSIDZ-JTYPQFNSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  38
• 可旋转键数：
  15
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  147
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  N-(3,4,6-tri-O-acetyl-2-fluoro-2-deoxy-β-D-glucopyranosyl)-4-(N'-benzyloxycarbonyl-N'-methylamino)butanamide 在 甲醇 、 palladium 10% on activated carbon 、 sodium hydride 、 碳酸氢钠 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基乙酰胺 、 mineral oil 为溶剂， 反应 33.0h， 生成 1-{N-[4-(3,4,6-tri-O-acetyl-2-fluoro-2-deoxy-β-D-glucopyranosyl)amino-4-oxobutyl]-N'-methylcarbamoyl}-5-fluorouracil
  参考文献：
  名称：

  Design, synthesis and in vitro drug release investigation of new potential 5-FU prodrugs

  摘要：

  In order to identify new efficient prodrugs of 5-fluorouracil (5-FU) and to develop an original targeting approach using 2-fluoro-2-deoxyglucose (FDG) as a potential drug carrier, eight original 5-FU derivatives were synthesized: 5-FU was attached by the N1 position of the pyrimidinic ring to the C1 position of the FDG structure either by direct coupling (2a) or via various spacers (3, 6a-c, 10b and 19). A new sensitive high-performance liquid chromatography method was developed to simultaneously quantify 5-FU and its derivatives in human plasma and other relevant media at physiological temperatures. Half-lives were determined from the degradation profiles of these conjugates. Slow degradation of compounds 2a, 3, 10b and 19 was observed in vitro at 37 degrees C, but no 5-FU release was noticed. By contrast, the in vitro drug release profiles of compounds 6a-c followed pseudo-first-order kinetics, and 5-FU was found in all the media. The antiproliferative activity of the eight compounds was assessed in vitro by a fluorometric assay against two human solid cancer cell lines and one healthy cell line. A correlation was found between the activities of the compounds and their ability to release 5-FU efficiently. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.04.010
• 作为产物：
  描述：

  4-{[(苄氧基)羰基](甲基)氨基}丁酸 、 3,4,6-Tri-O-acetyl-2-deoxy-2-fuoro-β-D-glucopyranosyl amine 在 氯甲酸乙酯 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 20.5h， 以22%的产率得到N-(3,4,6-tri-O-acetyl-2-fluoro-2-deoxy-β-D-glucopyranosyl)-4-(N'-benzyloxycarbonyl-N'-methylamino)butanamide
  参考文献：
  名称：

  Design, synthesis and in vitro drug release investigation of new potential 5-FU prodrugs

  摘要：

  In order to identify new efficient prodrugs of 5-fluorouracil (5-FU) and to develop an original targeting approach using 2-fluoro-2-deoxyglucose (FDG) as a potential drug carrier, eight original 5-FU derivatives were synthesized: 5-FU was attached by the N1 position of the pyrimidinic ring to the C1 position of the FDG structure either by direct coupling (2a) or via various spacers (3, 6a-c, 10b and 19). A new sensitive high-performance liquid chromatography method was developed to simultaneously quantify 5-FU and its derivatives in human plasma and other relevant media at physiological temperatures. Half-lives were determined from the degradation profiles of these conjugates. Slow degradation of compounds 2a, 3, 10b and 19 was observed in vitro at 37 degrees C, but no 5-FU release was noticed. By contrast, the in vitro drug release profiles of compounds 6a-c followed pseudo-first-order kinetics, and 5-FU was found in all the media. The antiproliferative activity of the eight compounds was assessed in vitro by a fluorometric assay against two human solid cancer cell lines and one healthy cell line. A correlation was found between the activities of the compounds and their ability to release 5-FU efficiently. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.04.010