2,8-Difluorocarbamazepine | 1408230-98-7

• 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-Difluorocarbamazepine
• 英文别名: 3,8-difluorobenzo[b][1]benzazepine-11-carboxamide
• CAS: 1408230-98-7
• 化学式: C₁₅H₁₀F₂N₂O
• 分子量: 272.254
• InChiKey: PWTMFMMOSKSVAV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 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：
  3

反应信息

• 作为产物：
  描述：

  5-氟吲哚 在 copper(l) iodide 、 potassium carbonate 、 三氟乙酸 、 L-脯氨酸 作用下， 以 二甲基亚砜 、 甲苯 为溶剂， 生成 2,8-Difluorocarbamazepine
  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

• [EN] FLUORINE CONTAINING COMPOUNDS AND METHODS OF USE THEREOF<br/>[FR] COMPOSÉS FLUORÉS ET LEURS PROCÉDÉS D'UTILISATION
  申请人：HARVARD COLLEGE

  公开号：WO2010081036A2

  公开（公告）日：2010-07-15

  Fluorinated compounds and methods of making fluorinated compounds are described herein.