5-[2-(2-carboxyethyl)phenylazo]-2-hydroxybenzoic acid tert-butyl ester | 1094772-24-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 偶氮苯
• 英文名称: 5-[2-(2-carboxyethyl)phenylazo]-2-hydroxybenzoic acid tert-butyl ester
• 英文别名: 3-[2-[[4-Hydroxy-3-[(2-methylpropan-2-yl)oxycarbonyl]phenyl]diazenyl]phenyl]propanoic acid
• CAS: 1094772-24-3
• 化学式: C₂₀H₂₂N₂O₅
• 分子量: 370.405
• InChiKey: QBABOWRYLCUKGI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  109
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  5-[2-(2-carboxyethyl)phenylazo]-2-hydroxybenzoic acid tert-butyl ester 、 塞来西布 在 4-二甲氨基吡啶 作用下， 以 二氯甲烷 、 叔丁醇 为溶剂， 生成 Tert-butyl 2-hydroxy-5-[[2-[3-[[4-[5-(4-methylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]phenyl]sulfonylamino]-3-oxopropyl]phenyl]diazenyl]benzoate
  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
• 作为产物：
  描述：

  3-(2-nitrosophenyl)propionic acid 、 2-甲基-2-丙基5-氨基-2-羟基苯甲酸酯 以 溶剂黄146 为溶剂， 反应 48.0h， 以69%的产率得到5-[2-(2-carboxyethyl)phenylazo]-2-hydroxybenzoic acid tert-butyl ester
  参考文献：
  名称：

  设计，合成和药理作用的环化激活类固醇前药结肠炎炎症性肠病针对。

  摘要：

  糖皮质激素用于治疗炎性肠病。其使用的限制是它们在到达结肠之前会先从GIT吸收，从而引起严重的全身性副作用。我们在这里报告了一种针对皮质类固醇靶向结肠的新型前药方法。该设计涉及连接一个21酯基团，该基团在转移到结肠的过程中会抑制吸收。前药被设计成通过结肠微生物区系释放，释放出环化释放类固醇的氨基酯。在鼠DSS模型中，前药5b之一与泼尼松龙一样有效，但是没有引起胸腺萎缩，胸腺萎缩是全身性类固醇作用的标志。

  DOI：

  10.1021/jm8016317

文献信息

• [EN] TARGETING DIAZO PRODRUGS FOR THE TREATMENT OF GASTROINTESTINAL DISEASES<br/>[FR] CIBLAGE DE PROMÉDICAMENTS DIAZO POUR LE TRAITEMENT DE MALADIES GASTRO-INTESTINALES
  申请人：TRINITY COLLEGE DUBLIN

  公开号：WO2009003970A1

  公开（公告）日：2009-01-08

  Provided herein are compounds, compositions and methods for decreasing NFkB DNA-binding activity in a patient comprising administering of a therapeutically effective amount of a compound or composition of the application to the patient to reduce, alleviate or treat various gastrointestinal diseases, such as inflammatory bowel disease (IBD).

  本文提供了一种减少患者NFkB DNA结合活性的化合物、组合物和方法，包括向患者施用本申请的化合物或组合物的治疗有效量，以减少、缓解或治疗各种胃肠疾病，如炎症性肠病（IBD）。
• [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
• Azo-reductase activated budesodine prodrugs for colon targeting
  作者：Juan F. Marquez Ruiz、Kinga Kedziora、Mary O’Reilly、Jacqueline Maguire、Brian Keogh、Henry Windle、Dermot P. Kelleher、John F. Gilmer

  DOI：10.1016/j.bmcl.2012.10.006

  日期：2012.12

  Budesodine is a synthetic glurocorticoid that undergoes substantial first pass metabolism, limiting systemic exposure. Its use in treatment of inflammatory bowel disease would benefit from a targeting strategy that could lead to a local topical effect, improving safety and increasing anti-inflammatory efficacy. A two-step prodrug strategy involving azoreduction/cyclization that we developed previously for prednisolone is here applied with some variations to budesonide. The budesodine prodrugs were tested using an in vitro azoreductase assay simulating human colonic microflora. The kinetics of amino steroid ester cyclization and its pH dependence was also evaluated. The stability of the prodrugs systems in simulated human duodenal and gastric fluid was evaluated to determine the likelihood of intact intestinal transit. The propionic acid derived prodrug 3 undergoes rapid activation by Clostridium perfingens and its putative reduction product cyclizes with acceptable rapidity when synthesized independently. These properties of 3 suggest that it has potential in management of ulcerative colitis. (c) 2012 Elsevier Ltd. All rights reserved.