3-[2-[[4-[(2-Methylpropan-2-yl)oxycarbonyl]phenyl]diazenyl]phenyl]propanoic acid | 1415405-03-6

• 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: 3-[2-[[4-[(2-Methylpropan-2-yl)oxycarbonyl]phenyl]diazenyl]phenyl]propanoic acid
• 英文别名: 3-[2-[[4-[(2-methylpropan-2-yl)oxycarbonyl]phenyl]diazenyl]phenyl]propanoic acid
• CAS: 1415405-03-6
• 化学式: C₂₀H₂₂N₂O₄
• 分子量: 354.406
• InChiKey: LSMCBFNUAZVAMV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  26
• 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：
  88.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-[2-[[4-[(2-Methylpropan-2-yl)oxycarbonyl]phenyl]diazenyl]phenyl]propanoic acid 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 4-[[2-[3-[2-[(8S,9S,10R,11S,13S,14S,17R)-11,17-dihydroxy-10,13-dimethyl-3-oxo-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-17-yl]-2-oxoethoxy]-3-oxopropyl]phenyl]diazenyl]benzoic acid
  参考文献：
  名称：

  Structure requirements for anaerobe processing of azo compounds: Implications for prodrug design

  摘要：

  This Letter generalizes the metabolism of the azo class of compounds by Clostridium perfringens, an anaerobe found in the human colon. A recently reported 5-aminosalicylic acid-based prednisolone prodrug was shown to release the drug when incubated with the bacteria, while the para-aminobenzoic acid (PABA) based analogue did not. Instead, it showed a new HPLC peak with a relatively close retention time to the parent which was identified by LCMS as the partially reduced hydrazine product. This Letter investigates azoreduction across a panel of substrates with varying degrees of electronic and steric similarity to the PABA-based compound. Azo compounds with an electron donating group on the azo-containing aromatic ring showed immediate disproportionation to their parent amines without any detection of hydrazine intermediates by HPLC. Compounds containing only electron withdrawing groups are partially and reversibly reduced to produce a stable detectable hydrazine. They do not disproportionate to their parent amines, but regenerate the parent azo compound. This incomplete reduction is relevant to the design of azo-based prodrugs and the toxicology of azo-based dyes. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.10.014
• 作为产物：
  描述：

  3-(2-nitrosophenyl)propionic acid 、 4-氨基苯甲酸叔丁酯 在 溶剂黄146 作用下， 生成 3-[2-[[4-[(2-Methylpropan-2-yl)oxycarbonyl]phenyl]diazenyl]phenyl]propanoic acid
  参考文献：
  名称：

  Structure requirements for anaerobe processing of azo compounds: Implications for prodrug design

  摘要：

  This Letter generalizes the metabolism of the azo class of compounds by Clostridium perfringens, an anaerobe found in the human colon. A recently reported 5-aminosalicylic acid-based prednisolone prodrug was shown to release the drug when incubated with the bacteria, while the para-aminobenzoic acid (PABA) based analogue did not. Instead, it showed a new HPLC peak with a relatively close retention time to the parent which was identified by LCMS as the partially reduced hydrazine product. This Letter investigates azoreduction across a panel of substrates with varying degrees of electronic and steric similarity to the PABA-based compound. Azo compounds with an electron donating group on the azo-containing aromatic ring showed immediate disproportionation to their parent amines without any detection of hydrazine intermediates by HPLC. Compounds containing only electron withdrawing groups are partially and reversibly reduced to produce a stable detectable hydrazine. They do not disproportionate to their parent amines, but regenerate the parent azo compound. This incomplete reduction is relevant to the design of azo-based prodrugs and the toxicology of azo-based dyes. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.10.014

文献信息

• 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.
• Structure requirements for anaerobe processing of azo compounds: Implications for prodrug design
  作者：Jason Gavin、Juan F. Marquez Ruiz、Kinga Kedziora、Henry Windle、Dermot P. Kelleher、John F. Gilmer

  DOI：10.1016/j.bmcl.2012.10.014

  日期：2012.12

  This Letter generalizes the metabolism of the azo class of compounds by Clostridium perfringens, an anaerobe found in the human colon. A recently reported 5-aminosalicylic acid-based prednisolone prodrug was shown to release the drug when incubated with the bacteria, while the para-aminobenzoic acid (PABA) based analogue did not. Instead, it showed a new HPLC peak with a relatively close retention time to the parent which was identified by LCMS as the partially reduced hydrazine product. This Letter investigates azoreduction across a panel of substrates with varying degrees of electronic and steric similarity to the PABA-based compound. Azo compounds with an electron donating group on the azo-containing aromatic ring showed immediate disproportionation to their parent amines without any detection of hydrazine intermediates by HPLC. Compounds containing only electron withdrawing groups are partially and reversibly reduced to produce a stable detectable hydrazine. They do not disproportionate to their parent amines, but regenerate the parent azo compound. This incomplete reduction is relevant to the design of azo-based prodrugs and the toxicology of azo-based dyes. (C) 2012 Elsevier Ltd. All rights reserved.