2,6-difluoro-4-(phenylsulfonamido)phenyl benzoate | 1248593-35-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 缩酚酸和缩酚酸环醚类
• 英文名称: 2,6-difluoro-4-(phenylsulfonamido)phenyl benzoate
• 英文别名: [4-(Benzenesulfonamido)-2,6-difluorophenyl] benzoate
• CAS: 1248593-35-2
• 化学式: C₁₉H₁₃F₂NO₄S
• 分子量: 389.379
• InChiKey: VGHHASKOLUHLAM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  80.8
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2,6-difluoro-4-(phenylsulfonamido)phenyl benzoate 、 4-溴-2-氟苄溴 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 72.5h， 生成
  参考文献：
  名称：

  A Diverse Series of Substituted Benzenesulfonamides as Aldose Reductase Inhibitors with Antioxidant Activity: Design, Synthesis, and in Vitro Activity

  摘要：

  We have previously reported the successful replacement of a carboxylic acid functionality with that of a difluorophenolic group on the known aldose reductase inhibitors (ARIs) of 2-(phenylsulfonamido)-acetic acid chemotype. In the present work, based on bioisosteric principles, additional 2,6-difluorophenol and tetrazole, methylsulfonylamide, and isoxazolidin-3-one phenylsulfonamide derivatives were synthesized and tested in vitro in protocols primarily related to the long-term diabetic complications. Most of the compounds were found as ARIs at IC50 < 100 mu M, while the introduction of the 4-bromo-2-fluorobenzyl group in a phenylsulfonamidodifluorophenol structure resulted in a compound (4c) presenting a submicromolar inhibitory profile. However, the derivatives of tetrazole, methylsulfonylamine, and the (R)-enantiomer of isoxazolidin-3-one did not exhibit appreciable A R activity. The selectivity of the active A R Is is also discussed. Furthermore, the synthesized compounds exhibited potent antioxidant potential (homogeneous and heterogeneous systems).

  DOI：

  10.1021/jm101008m
• 作为产物：
  描述：

  N-(3,5-Difluoro-4-hydroxyphenyl)benzenesulfonamide 、 苯甲酰氯 在 三乙胺 作用下， 以 1,4-二氧六环 为溶剂， 以73.4%的产率得到2,6-difluoro-4-(phenylsulfonamido)phenyl benzoate
  参考文献：
  名称：

  A Diverse Series of Substituted Benzenesulfonamides as Aldose Reductase Inhibitors with Antioxidant Activity: Design, Synthesis, and in Vitro Activity

  摘要：

  We have previously reported the successful replacement of a carboxylic acid functionality with that of a difluorophenolic group on the known aldose reductase inhibitors (ARIs) of 2-(phenylsulfonamido)-acetic acid chemotype. In the present work, based on bioisosteric principles, additional 2,6-difluorophenol and tetrazole, methylsulfonylamide, and isoxazolidin-3-one phenylsulfonamide derivatives were synthesized and tested in vitro in protocols primarily related to the long-term diabetic complications. Most of the compounds were found as ARIs at IC50 < 100 mu M, while the introduction of the 4-bromo-2-fluorobenzyl group in a phenylsulfonamidodifluorophenol structure resulted in a compound (4c) presenting a submicromolar inhibitory profile. However, the derivatives of tetrazole, methylsulfonylamine, and the (R)-enantiomer of isoxazolidin-3-one did not exhibit appreciable A R activity. The selectivity of the active A R Is is also discussed. Furthermore, the synthesized compounds exhibited potent antioxidant potential (homogeneous and heterogeneous systems).

  DOI：

  10.1021/jm101008m

文献信息

• A Diverse Series of Substituted Benzenesulfonamides as Aldose Reductase Inhibitors with Antioxidant Activity: Design, Synthesis, and in Vitro Activity
  作者：Polyxeni Alexiou、Vassilis J. Demopoulos

  DOI：10.1021/jm101008m

  日期：2010.11.11

  We have previously reported the successful replacement of a carboxylic acid functionality with that of a difluorophenolic group on the known aldose reductase inhibitors (ARIs) of 2-(phenylsulfonamido)-acetic acid chemotype. In the present work, based on bioisosteric principles, additional 2,6-difluorophenol and tetrazole, methylsulfonylamide, and isoxazolidin-3-one phenylsulfonamide derivatives were synthesized and tested in vitro in protocols primarily related to the long-term diabetic complications. Most of the compounds were found as ARIs at IC50 < 100 mu M, while the introduction of the 4-bromo-2-fluorobenzyl group in a phenylsulfonamidodifluorophenol structure resulted in a compound (4c) presenting a submicromolar inhibitory profile. However, the derivatives of tetrazole, methylsulfonylamine, and the (R)-enantiomer of isoxazolidin-3-one did not exhibit appreciable A R activity. The selectivity of the active A R Is is also discussed. Furthermore, the synthesized compounds exhibited potent antioxidant potential (homogeneous and heterogeneous systems).