(E)-2-(6-((2,6-dichlorophenyl)imino)-3-oxocyclohexa-1,4-dien-1-yl)acetic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (E)-2-(6-((2,6-dichlorophenyl)imino)-3-oxocyclohexa-1,4-dien-1-yl)acetic acid
• 英文别名: 5-hydroxydiclofenacquinoneimine；diclofenac-2,5-quinone imine
• 化学式: C₁₄H₉Cl₂NO₃
• 分子量: 310.136
• InChiKey: GTSUHSLLLCOPRM-SFQUDFHCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.61
• 重原子数：
  20.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  66.73
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为产物：
  描述：

  双氯芬酸 以 水 、 乙腈 为溶剂， 以20%的产率得到(E)-2-(6-((2,6-dichlorophenyl)imino)-3-oxocyclohexa-1,4-dien-1-yl)acetic acid
  参考文献：
  名称：

  Preparative Microfluidic Electrosynthesis of Drug Metabolites

  摘要：

  In vivo, a drug molecule undergoes its first chemical transformation within the liver via CYP450-catalyzed oxidation. The chemical outcome of the first pass hepatic oxidation is key information to any drug development process. Electrochemistry can be used to simulate CYP450 oxidation, yet it is often confined to the analytical scale, hampering product isolation and full characterization. In an effort to replicate hepatic oxidations, while retaining high throughput at the preparative scale, microfluidic technology and electrochemistry are combined in this study by using a microfluidic electrochemical cell. Several commercial drugs were subjected to continuous-flow electrolysis. They were chosen for their various chemical reactivity: their metabolites in vivo are generated via aromatic hydroxylation, alkyl oxidation, glutathione conjugation, or sulfoxidation. It is demonstrated that such metabolites can be synthesized by flow electrolysis at the 10 to 100 mg scale, and the purified products are fully characterized.

  DOI：

  10.1021/ml400316p

文献信息

• Oxidation of Diclofenac to Reactive Intermediates by Neutrophils, Myeloperoxidase, and Hypochlorous Acid
  作者：Gohachiro Miyamoto、Nasir Zahid、Jack P. Uetrecht

  DOI：10.1021/tx960190k

  日期：1997.4.1

  Diclofenac is associated with a low, but significant, incidence of hepatotoxicity and bone marrow toxicity. It has been suggested that this could be due to a reactive acyl glucuronide. An alternative hypothesis is that an oxidative reactive metabolite could be responsible for such reactions and such metabolites formed by the enzymes present in neutrophils could be responsible for bone marrow toxicity. Others had reported the formation of 2,2'-dihydroxyazobenzene during the oxidation of diclofenac by myeloperoxidase/hydrogen peroxide. In contrast, in similar experiments we did not find evidence for the formation of 2,2'-dihydroxyazobenzene, but we did find several products, including a reactive iminoquinone. The same iminoquinone was formed by the oxidation of 5-hydroxydiclofenac. This iminoquinone was also formed by oxidation of diclofenac by HOCl or by activated neutrophils. It reacted with glutathione to form a conjugate. 5-Hydroxydiclofenac is also a major hepatic metabolite of diclofenac, and we found that rat hepatic microsomes oxidized 5-hydroxydiclofenac to the iminoquinone which was trapped with glutathione. This reactive metabolite represents another possible cause of the idiosyncratic reactions associated with the use of diclofenac.
• Preparative Microfluidic Electrosynthesis of Drug Metabolites
  作者：Romain Stalder、Gregory P. Roth

  DOI：10.1021/ml400316p

  日期：2013.11.14

  In vivo, a drug molecule undergoes its first chemical transformation within the liver via CYP450-catalyzed oxidation. The chemical outcome of the first pass hepatic oxidation is key information to any drug development process. Electrochemistry can be used to simulate CYP450 oxidation, yet it is often confined to the analytical scale, hampering product isolation and full characterization. In an effort to replicate hepatic oxidations, while retaining high throughput at the preparative scale, microfluidic technology and electrochemistry are combined in this study by using a microfluidic electrochemical cell. Several commercial drugs were subjected to continuous-flow electrolysis. They were chosen for their various chemical reactivity: their metabolites in vivo are generated via aromatic hydroxylation, alkyl oxidation, glutathione conjugation, or sulfoxidation. It is demonstrated that such metabolites can be synthesized by flow electrolysis at the 10 to 100 mg scale, and the purified products are fully characterized.