(E),(Z)-(6-chloro-11H-dibenzazepin-11-ylidene)acetonitrile

• 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: (E),(Z)-(6-chloro-11H-dibenzazepin-11-ylidene)acetonitrile
• 英文别名: 2-(6-chlorobenzo[c][1]benzazepin-11-ylidene)acetonitrile
• 化学式: C₁₆H₉ClN₂
• 分子量: 264.714
• InChiKey: AXNGFZCXONRKPD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.27
• 重原子数：
  19.0
• 可旋转键数：
  0.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  36.15
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  (E),(Z)-(6-chloro-11H-dibenzazepin-11-ylidene)acetonitrile 在 双氧水 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 5.0h， 生成 (Z)-[6-(4-methyl-4-oxy-1-piperazinyl)-11H-dibenz[b,e]azepin-11-ylidene]acetonitrile
  参考文献：
  名称：

  Tricyclic epines. Novel (E)- and (Z)-11H-dibenz[b,e]azepines as potential central nervous system agents. Variation of the basic side chain

  摘要：

  The synthesis and pharmacological activity of new (E),(Z)-[6-(alkylamino)-11H-dibenz[b,e]azepin-11- ylidene]acetonitriles 12-45 and (E),(Z)-[6-(aminoalkoxy)-11H-dibenz[b,e]azepin-11-ylidene] acetonitriles 46-51 are described. The introduction of the cyanomethylene group into the 11-position of the 11H-dibenz[b,e]azepine framework has been carried out by a Wittig-Horner reaction under mild conditions. The (E),(Z) isomers were separated by fractional crystallization, assignment being achieved by X-ray analysis. A number of (E),(Z)-[6-(alkylamino)-11H-dibenz-[b,e]azepin-11-ylidene] acetonitriles (12, 14, 16, 20) show potent neuroleptic activity (2-7 times that of clozapine) in animal tests. The screening included tests for sedative and anticholinergic activity in mice, apomorphine and tryptamine antagonism in rats, and muscle-relaxing activity in rabbits. The divergence in the activity profile in the case of the separated (E),(Z) isomers has been observed as an interesting new aspect: the (Z) isomers show a significantly higher sedative and muscle-relaxant activity, whereas the (E) isomers possess a higher anticholinergic efficacy and somewhat greater apomorphine antagonism. Broad changes in the basic side chain were made in order to investigate structure-activity relationships. The important geometrical parameters for the molecules, obtained by X-ray analysis, were compared with the corresponding features in dopamine agonists and antagonists.

  DOI：

  10.1021/jm00160a015
• 作为产物：
  描述：

  5H-二苯并[b,e]氮杂卓-6,11-二酮 在 sodium methylate 、 N,N-二甲基苯胺 、 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成 (E),(Z)-(6-chloro-11H-dibenzazepin-11-ylidene)acetonitrile
  参考文献：
  名称：

  Tricyclic epines. Novel (E)- and (Z)-11H-dibenz[b,e]azepines as potential central nervous system agents. Variation of the basic side chain

  摘要：

  The synthesis and pharmacological activity of new (E),(Z)-[6-(alkylamino)-11H-dibenz[b,e]azepin-11- ylidene]acetonitriles 12-45 and (E),(Z)-[6-(aminoalkoxy)-11H-dibenz[b,e]azepin-11-ylidene] acetonitriles 46-51 are described. The introduction of the cyanomethylene group into the 11-position of the 11H-dibenz[b,e]azepine framework has been carried out by a Wittig-Horner reaction under mild conditions. The (E),(Z) isomers were separated by fractional crystallization, assignment being achieved by X-ray analysis. A number of (E),(Z)-[6-(alkylamino)-11H-dibenz-[b,e]azepin-11-ylidene] acetonitriles (12, 14, 16, 20) show potent neuroleptic activity (2-7 times that of clozapine) in animal tests. The screening included tests for sedative and anticholinergic activity in mice, apomorphine and tryptamine antagonism in rats, and muscle-relaxing activity in rabbits. The divergence in the activity profile in the case of the separated (E),(Z) isomers has been observed as an interesting new aspect: the (Z) isomers show a significantly higher sedative and muscle-relaxant activity, whereas the (E) isomers possess a higher anticholinergic efficacy and somewhat greater apomorphine antagonism. Broad changes in the basic side chain were made in order to investigate structure-activity relationships. The important geometrical parameters for the molecules, obtained by X-ray analysis, were compared with the corresponding features in dopamine agonists and antagonists.

  DOI：

  10.1021/jm00160a015

文献信息

• Tricyclic epines. Novel (E)- and (Z)-11H-dibenz[b,e]azepines as potential central nervous system agents. Variation of the basic side chain
  作者：Gerd Steiner、Albrecht Franke、Erich Haedicke、Dieter Lenke、Hans Juergen Teschendorf、Hans Peter Hofmann、Horst Kreiskott、Wolfgang Worstmann

  DOI：10.1021/jm00160a015

  日期：1986.10

  The synthesis and pharmacological activity of new (E),(Z)-[6-(alkylamino)-11H-dibenz[b,e]azepin-11- ylidene]acetonitriles 12-45 and (E),(Z)-[6-(aminoalkoxy)-11H-dibenz[b,e]azepin-11-ylidene] acetonitriles 46-51 are described. The introduction of the cyanomethylene group into the 11-position of the 11H-dibenz[b,e]azepine framework has been carried out by a Wittig-Horner reaction under mild conditions. The (E),(Z) isomers were separated by fractional crystallization, assignment being achieved by X-ray analysis. A number of (E),(Z)-[6-(alkylamino)-11H-dibenz-[b,e]azepin-11-ylidene] acetonitriles (12, 14, 16, 20) show potent neuroleptic activity (2-7 times that of clozapine) in animal tests. The screening included tests for sedative and anticholinergic activity in mice, apomorphine and tryptamine antagonism in rats, and muscle-relaxing activity in rabbits. The divergence in the activity profile in the case of the separated (E),(Z) isomers has been observed as an interesting new aspect: the (Z) isomers show a significantly higher sedative and muscle-relaxant activity, whereas the (E) isomers possess a higher anticholinergic efficacy and somewhat greater apomorphine antagonism. Broad changes in the basic side chain were made in order to investigate structure-activity relationships. The important geometrical parameters for the molecules, obtained by X-ray analysis, were compared with the corresponding features in dopamine agonists and antagonists.