5-(3-(phenylsulfonyl)ureido)pyridine-2-sulfonamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 5-(3-(phenylsulfonyl)ureido)pyridine-2-sulfonamide
• 英文别名: 1-(Benzenesulfonyl)-3-(6-sulfamoylpyridin-3-yl)urea；1-(benzenesulfonyl)-3-(6-sulfamoylpyridin-3-yl)urea
• 化学式: C₁₂H₁₂N₄O₅S₂
• 分子量: 356.383
• InChiKey: QTRXSDAPWFBZQU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  165
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  5-氨基-2-吡啶磺酰胺 、 异氰酸苯磺酰酯 以 丙酮 为溶剂， 以83%的产率得到5-(3-(phenylsulfonyl)ureido)pyridine-2-sulfonamide
  参考文献：
  名称：

  Structural Insights on Carbonic Anhydrase Inhibitory Action, Isoform Selectivity, and Potency of Sulfonamides and Coumarins Incorporating Arylsulfonylureido Groups

  摘要：

  Sulfonamides and coumarins incorporating arylsulfonylureido tails were prepared and assayed as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). Some derivatives incorporating 3-pyridinesulfonamide and arylsulfonylureoido fragments were low nanomolar inhibitors of isoforms CA II and XII (upregulated or overexpressed in glaucoma) and showed effective in vivo intraocular pressure lowering effects in an animal model of the disease, which were several times better compared to those of the antiglaucoma drug dorzolamide. By means of X-ray crystallography of adducts of several sulfonamides with CA II, the effective inhibitory properties were rationalized at the molecular level. The coumarins were ineffective as hCA I and II inhibitors but showed low nanomolar activity for the inhibition of the tumor-associated isoforms hCA IX and XII. The presence of arylsulfonylureido tails in these CA inhibitors possessing quite different mechanisms of action led to highly effective and isoform-selective compounds targeting enzymes involved in severe pathologies such as glaucoma or cancer.

  DOI：

  10.1021/jm501314c

文献信息

• Structural Insights on Carbonic Anhydrase Inhibitory Action, Isoform Selectivity, and Potency of Sulfonamides and Coumarins Incorporating Arylsulfonylureido Groups
  作者：Murat Bozdag、Marta Ferraroni、Fabrizio Carta、Daniela Vullo、Laura Lucarini、Elisabetta Orlandini、Armando Rossello、Elisa Nuti、Andrea Scozzafava、Emanuela Masini、Claudiu T. Supuran

  DOI：10.1021/jm501314c

  日期：2014.11.13

  Sulfonamides and coumarins incorporating arylsulfonylureido tails were prepared and assayed as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). Some derivatives incorporating 3-pyridinesulfonamide and arylsulfonylureoido fragments were low nanomolar inhibitors of isoforms CA II and XII (upregulated or overexpressed in glaucoma) and showed effective in vivo intraocular pressure lowering effects in an animal model of the disease, which were several times better compared to those of the antiglaucoma drug dorzolamide. By means of X-ray crystallography of adducts of several sulfonamides with CA II, the effective inhibitory properties were rationalized at the molecular level. The coumarins were ineffective as hCA I and II inhibitors but showed low nanomolar activity for the inhibition of the tumor-associated isoforms hCA IX and XII. The presence of arylsulfonylureido tails in these CA inhibitors possessing quite different mechanisms of action led to highly effective and isoform-selective compounds targeting enzymes involved in severe pathologies such as glaucoma or cancer.