2-hydroxy-5-(2-{3-oxo-3-[4-(5-p-tolyl-3-trifluoromethyl-pyrazol-1-yl)-benzenesulfonylamino]-propyl}-phenylazo)benzoic acid | 1233497-32-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-hydroxy-5-(2-{3-oxo-3-[4-(5-p-tolyl-3-trifluoromethyl-pyrazol-1-yl)-benzenesulfonylamino]-propyl}-phenylazo)benzoic acid
• 英文别名: 2-Hydroxy-5-[[2-[3-[[4-[5-(4-methylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]phenyl]sulfonylamino]-3-oxopropyl]phenyl]diazenyl]benzoic acid
• CAS: 1233497-32-9
• 化学式: C₃₃H₂₆F₃N₅O₆S
• 分子量: 677.661
• InChiKey: MZZZZHVRBZCOHQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7
• 重原子数：
  48
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  172
• 氢给体数：
  3
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  3-(2-aminophenyl)-N-[4-[5-(4-methylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]phenyl]sulfonylpropanamide 在 4-二甲氨基吡啶 、 三氟乙酸 作用下， 以 二氯甲烷 、 叔丁醇 为溶剂， 反应 4.0h， 生成 2-hydroxy-5-(2-{3-oxo-3-[4-(5-p-tolyl-3-trifluoromethyl-pyrazol-1-yl)-benzenesulfonylamino]-propyl}-phenylazo)benzoic acid
  参考文献：
  名称：

  A double prodrug system for colon targeting of benzenesulfonamide COX-2 inhibitors

  摘要：

  The design, synthesis and delivery potential of a new type of benzenesulfonamide cyclo-oxygenase-2 (COX-2) inhibitor prodrug is investigated using celecoxib. The approach involves a double prodrug that is activated first by azoreductases and then by cyclization triggering drug release.We studied the intramolecular aminolysis of the acylsulfonamide. The cyclization was surprisingly rapid at physiological pH and very fast at pH 5. The prodrug is activated specifically under conditions found in the colon but highly stable in the presence of human and rodent intestinal extracts. Finally, the prototype with celecoxib was transported much more slowly in the Caco-2 transepithelial model than the parent. The design therefore shows significant promise for the site specific delivery of benzenesulfonamide COX-2 inhibitors to the colon. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.09.071

文献信息

• [EN] TARGETING PRODRUGS AND COMPOSITIONS FOR THE TREATMENT OF GASTROINTESTINAL DISEASES<br/>[FR] PROMÉDICAMENTS CIBLANTS ET COMPOSITIONS DESTINÉS AU TRAITEMENT DE MALADIES GASTRO-INTESTINALES
  申请人：TRINITY COLLEGE DUBLIN

  公开号：WO2010072734A3

  公开（公告）日：2010-08-19