2,8-dibromo-5H-dibenz[b,f]azepine-5-carboxamide | 1408231-02-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 英文名称: 2,8-dibromo-5H-dibenz[b,f]azepine-5-carboxamide
• 英文别名: 2,8-Dibromocarbamazepine；3,8-dibromobenzo[b][1]benzazepine-11-carboxamide
• CAS: 1408231-02-6
• 化学式: C₁₅H₁₀Br₂N₂O
• 分子量: 394.065
• InChiKey: OZSWYJPYSFMYDI-UHFFFAOYSA-N

物化性质

• 沸点：
  524.9±60.0 °C(predicted)
• 密度：
  1.799±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  20
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  46.3
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为产物：
  描述：

  亚氨基二苄 在 4-二甲氨基吡啶 、 N-溴代丁二酰亚胺(NBS) 、 三氟甲苯 、 三氟乙酸 、 1,1'-偶氮(氰基环己烷) 作用下， 以 氯仿 、 甲苯 为溶剂， 反应 15.0h， 生成 2,8-dibromo-5H-dibenz[b,f]azepine-5-carboxamide
  参考文献：
  名称：

  Haloarene Derivatives of Carbamazepine with Reduced Bioactivation Liabilities: 2-Monohalo and 2,8-Dihalo Derivatives

  摘要：

  The anticonvulsant carbamazepine 1 is associated with aderse drug reactions (ADRs), including hepatotaxicity; oxidative Metabolism of 1 has been implicated in the pathogenesis of the ADRs. We report the synthesis and evaluation of 2-monohalo and 2,8-dihalo analogues of 1 that were intended to minimize reactive metabolite formation via arene oxidation and 10,11-epoxidation. Halo analogues were obtained either by rearrangement of halogenated N-arylindoles or from specifically halogenated iminodibenzyl derivatives. In rat hepatocytes, none of the :analogues underwent oxidative dehalogenation or glutathiohe adduction. Some formation of the 10,11 epoxide still. occurred, but :aromatic hydroxylation was not seen with the exception of 2-fluoro, which allowed minor monohydroxylation. Complete inhibition of aromatic hydroxylation required at least monochlorination or difluorination of 1. In human liver microsoms, difluoro analogue 5b underwent 10,11-epoxidation but gave no arene oxidation.

  DOI：

  10.1021/jm301013n

文献信息

• Convenient syntheses of halo-dibenz[b,f]azepines and carbamazepine analogues via N-arylindoles
  作者：Emma-Claire Elliott、James L. Maggs、B. Kevin Park、Paul M. O'Neill、Andrew V. Stachulski

  DOI：10.1039/c3ob41252k

  日期：——

  naturally sought short and efficient methods for our target compounds. In the following report we present an effective two-step synthesis of a range of dibenz[b,f]azepines from appropriate indoles via N-arylation, then acid-catalysed rearrangement, with a critical analysis of other approaches. We showed earlier that this route was effective for fluoro analogues and here present a broader review of its

  具有单一10,11键的dibenz [ b，f ]氮杂杂环系统和相关分子是处方明确的药物分子的重要模板，尤其是卡马西平（抗惊厥药），氯米帕明和丙咪嗪（抗抑郁药）。我们结合代谢和免疫学研究，合成了一系列卤代卡马西平类似物，作为结构代谢和超敏作用的探针，并已发表了有关其代谢行为的文章。尽管可以通过多种合成途径获得此类类似物，但我们自然地为我们的目标化合物寻求了简便而有效的方法。在下面的报告中，我们介绍了从适当的吲哚类化合物合成一系列dibenz [ b，f ] azepines的有效两步法通过N-芳基化，然后进行酸催化重排，并对其他方法进行严格分析。较早前我们表明，该方法对氟类似物有效，在此我们对其范围进行了更广泛的综述。卡马西平的5-（羧酰胺基）侧链可以通过各种方式添加，从而使总体上可以方便地获取药物分子。
• Haloarene Derivatives of Carbamazepine with Reduced Bioactivation Liabilities: 2-Monohalo and 2,8-Dihalo Derivatives
  作者：Emma-Claire Elliott、Sophie L. Regan、James L. Maggs、Elizabeth R. Bowkett、Laura J. Parry、Dominic P. Williams、B. Kevin Park、Andrew V. Stachulski

  DOI：10.1021/jm301013n

  日期：2012.11.26

  The anticonvulsant carbamazepine 1 is associated with aderse drug reactions (ADRs), including hepatotaxicity; oxidative Metabolism of 1 has been implicated in the pathogenesis of the ADRs. We report the synthesis and evaluation of 2-monohalo and 2,8-dihalo analogues of 1 that were intended to minimize reactive metabolite formation via arene oxidation and 10,11-epoxidation. Halo analogues were obtained either by rearrangement of halogenated N-arylindoles or from specifically halogenated iminodibenzyl derivatives. In rat hepatocytes, none of the :analogues underwent oxidative dehalogenation or glutathiohe adduction. Some formation of the 10,11 epoxide still. occurred, but :aromatic hydroxylation was not seen with the exception of 2-fluoro, which allowed minor monohydroxylation. Complete inhibition of aromatic hydroxylation required at least monochlorination or difluorination of 1. In human liver microsoms, difluoro analogue 5b underwent 10,11-epoxidation but gave no arene oxidation.