1-{2-[N-(2-hydroxymethylphenyl)-2-nitrobenzenesulfonamido]-1-methoxyethyl}-5-fluorouracil

• 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: 1-{2-[N-(2-hydroxymethylphenyl)-2-nitrobenzenesulfonamido]-1-methoxyethyl}-5-fluorouracil
• 英文别名: N-[2-(5-fluoro-2,4-dioxopyrimidin-1-yl)-2-methoxyethyl]-N-[2-(hydroxymethyl)phenyl]-2-nitrobenzenesulfonamide
• 化学式: C₂₀H₁₉FN₄O₈S
• 分子量: 494.457
• InChiKey: VKVDYXVSLWEQHG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  170
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  1-{2-[N-(2-hydroxymethylphenyl)-2-nitrobenzenesulfonamido]-1-methoxyethyl}-5-fluorouracil 在 tin(II) chloride dihdyrate 、 碳酸氢钠 作用下， 以 乙醇 、 水 为溶剂， 反应 1.0h， 以50%的产率得到1-{2-[2-amino-N-(2-hydroxymethylphenyl)benzenesulfonamido]-1-methoxyethyl}-5-fluorouracil
  参考文献：
  名称：

  Anticancer activity and cDNA microarray studies of a (RS)-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-yl]-6-chloro-9H-purine, and an acyclic (RS)-O,N-acetalic 6-chloro-7H-purine

  摘要：

  Completing a SAR study, a series of (RS)-6-substituted-7- or 9-(1,2,3,5-tetrahydro-4,1-benzoxazepine-3-yl)-7H or 9H-purines was previously prepared. The most potent antiproliferative agent against the MCF-7 adenocarcinoma cell line that belongs to the benzoxazepine O,N-acetalic family is (RS)-9-[1-(9H-fluorenyl-9-methoxycarbonyl)-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-yl]-6-chloro-9H-purine (16, IC50 = 0.67 +/- 0.18 mu M), whilst (RS)-7-{2-(N-hydroxymethylphenyl)-2-nitrobenzenesulfonamido]-1-methoxyethyl}-6-chloro-7H-purine (37) shows the lowest IC50 value between the family of acyclic O,N-acetals (IC50 = 3.25 +/- 0.23 mu M). Moreover, 16 showed the better in vitro Therapeutic Index in breast cell lines (3.19), whilst 37 was found to be 3.69-fold more active against HT-29 human colon cancer cell line than versus IEC-6 normal rat intestinal epithelial cell line. The global apoptotic cells caused by 16 and 37 against MCF-7 were 80.08% and 54.85% of cell population after 48 h, respectively. cDNA microarray technology reveals potential drug targets, which are mainly centred on positive apoptosis regulatory pathway genes, and the repression of genes involved in carcinogenesis, proliferation and tumour invasion. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.05.047
• 作为产物：
  描述：

  5-氟脲嘧啶 、 1-(2-nitrobenzenesulfonyl)-3-methoxy-1,2,3,5-tetrahydro-4,1-benzoxazepine 在 三甲基氯硅烷 、 四氯化锡 、 六甲基二硅氮烷 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 51.0h， 以30%的产率得到1-{2-[N-(2-hydroxymethylphenyl)-2-nitrobenzenesulfonamido]-1-methoxyethyl}-5-fluorouracil
  参考文献：
  名称：

  控制5-氟尿嘧啶，尿嘧啶和四氢苯并氧杂氮杂O，O-缩醛在氮原子上带有电子吸收基团的产物比率的因素的研究

  摘要：

  （RS）-1-（2-硝基苯磺酰基）-和（RS）-1-（4-硝基苯磺酰基）-3-甲氧基-1,2,3,5-四氢-4,1-苯并x庚因是比1-更好的底物酰基-3-甲氧基-1,2,3,5-四氢-4,1-苯并x并庚因衍生物，在路易斯酸介导的与嘧啶碱的缩合反应中生成O，N-乙缩醛。乙腈，氯化锡，50°C和高于48小时的反应时间是此类缩合反应的最佳条件。在这些条件下，5-氟尿嘧啶优选通过其N -1''位置连接至氨基碳，而尿嘧啶片段的连接通过N -3''或N-1''分别为环状或非环状产物。分析和讨论了影响反应过程的原因。所述的检查1核磁共振光谱揭示了单一形式的存在下，仲胺11和两种构象异构体的叔磺酰胺7a中，b，图9a，b，和图10b以及用于酰胺7D和13，具有以下的分布：7a，59/41; 7b，53/47；9a，52/48；9b，59/41; 10b，56/44；7d，50/50; 13，80/20。随着温度的升高，7b的1

  DOI：

  10.1021/jo052167m

文献信息

• Study of the Factors that Control the Ratio of the Products between 5-Fluorouracil, Uracil, and Tetrahydrobenzoxazepine <i>O</i>,<i>O</i>-Acetals Bearing Electron-Withdrawing Groups on the Nitrogen Atom
  作者：Mónica Díaz-Gavilán、José A. Gómez-Vidal、Antonio Entrena、Miguel A. Gallo、Antonio Espinosa、Joaquín M. Campos

  DOI：10.1021/jo052167m

  日期：2006.2.1

  derivatives for the Lewis acid mediated condensation reaction with pyrimidine bases to give O,N-acetals. Acetonitrile, stannic chloride, 50 °C, and a reaction time higher than 48 h are the optimum conditions for such condensation reactions. Under these conditions, 5-fluorouracil preferably links to the aminalic carbon through its N-1‘ ‘ position, while the attachment of the uracil fragment is through N-3‘ ‘

  （RS）-1-（2-硝基苯磺酰基）-和（RS）-1-（4-硝基苯磺酰基）-3-甲氧基-1,2,3,5-四氢-4,1-苯并x庚因是比1-更好的底物酰基-3-甲氧基-1,2,3,5-四氢-4,1-苯并x并庚因衍生物，在路易斯酸介导的与嘧啶碱的缩合反应中生成O，N-乙缩醛。乙腈，氯化锡，50°C和高于48小时的反应时间是此类缩合反应的最佳条件。在这些条件下，5-氟尿嘧啶优选通过其N -1''位置连接至氨基碳，而尿嘧啶片段的连接通过N -3''或N-1''分别为环状或非环状产物。分析和讨论了影响反应过程的原因。所述的检查1核磁共振光谱揭示了单一形式的存在下，仲胺11和两种构象异构体的叔磺酰胺7a中，b，图9a，b，和图10b以及用于酰胺7D和13，具有以下的分布：7a，59/41; 7b，53/47；9a，52/48；9b，59/41; 10b，56/44；7d，50/50; 13，80/20。随着温度的升高，7b的1
• Anticancer activity and cDNA microarray studies of a (RS)-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-yl]-6-chloro-9H-purine, and an acyclic (RS)-O,N-acetalic 6-chloro-7H-purine
  作者：Octavio Caba、Mónica Díaz-Gavilán、Fernando Rodríguez-Serrano、Houria Boulaiz、Antonia Aránega、Miguel A. Gallo、Juan A. Marchal、Joaquín M. Campos

  DOI：10.1016/j.ejmech.2011.05.047

  日期：2011.9

  Completing a SAR study, a series of (RS)-6-substituted-7- or 9-(1,2,3,5-tetrahydro-4,1-benzoxazepine-3-yl)-7H or 9H-purines was previously prepared. The most potent antiproliferative agent against the MCF-7 adenocarcinoma cell line that belongs to the benzoxazepine O,N-acetalic family is (RS)-9-[1-(9H-fluorenyl-9-methoxycarbonyl)-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-yl]-6-chloro-9H-purine (16, IC50 = 0.67 +/- 0.18 mu M), whilst (RS)-7-2-(N-hydroxymethylphenyl)-2-nitrobenzenesulfonamido]-1-methoxyethyl}-6-chloro-7H-purine (37) shows the lowest IC50 value between the family of acyclic O,N-acetals (IC50 = 3.25 +/- 0.23 mu M). Moreover, 16 showed the better in vitro Therapeutic Index in breast cell lines (3.19), whilst 37 was found to be 3.69-fold more active against HT-29 human colon cancer cell line than versus IEC-6 normal rat intestinal epithelial cell line. The global apoptotic cells caused by 16 and 37 against MCF-7 were 80.08% and 54.85% of cell population after 48 h, respectively. cDNA microarray technology reveals potential drug targets, which are mainly centred on positive apoptosis regulatory pathway genes, and the repression of genes involved in carcinogenesis, proliferation and tumour invasion. (C) 2011 Elsevier Masson SAS. All rights reserved.