5,10-dihydro-4H-thieno<3,2-c><1>benzazepin-4-one | 42239-40-7

• 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: 5,10-dihydro-4H-thieno<3,2-c><1>benzazepin-4-one
• 英文别名: 5,10-dihydro-4H-thieno[3,2-c][1]benzazepin-4-one；5,10-dihydro-benzo[b]thieno[2,3-e]azepin-4-one；4,5-dihydro-10H-thieno[3,2-c][1]benzazepin-4-one；4,5-Dihydro-10H-thieno<3,2-c>-(1)benzazepin-4-on；5,10-dihydrothieno[3,2-c][1]benzazepin-4-one
• CAS: 42239-40-7
• 化学式: C₁₂H₉NOS
• 分子量: 215.276
• InChiKey: JJOCTMYAGFLYRV-UHFFFAOYSA-N

物化性质

• 熔点：
  244-247 °C(Solv: acetone (67-64-1))
• 沸点：
  295.1±19.0 °C(Predicted)
• 密度：
  1.298±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  57.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5,10-dihydro-4H-thieno<3,2-c><1>benzazepin-4-one 在 劳森试剂 作用下， 以 甲苯 为溶剂， 反应 2.6h， 以0.28 g的产率得到5,10-Dihydrothieno[3,2-c][1]benzazepine-4-thione
  参考文献：
  名称：

  Behavioral Approach to Nondyskinetic Dopamine Antagonists:  Identification of Seroquel

  摘要：

  A great need exists for antipsychotic drugs which will not induce extrapyramidal symptoms (EPS) and tardive dyskinesias (TDs). These side effects are deemed to be a consequence of nonselective blockade of nigrostriatal and mesolimbic dopamine D2 receptors. Nondyskinetic clozapine (1) is a low-potency D2 dopamine receptor antagonist which appears to act selectively in the mesolimbic area. In this work dopamine antagonism was assessed in two mouse behavioral assays: antagonism of apomorphine-induced climbing and antagonism of apomorphine-induced disruption of swimming. The potential for the liability of dyskinesias was determined in haloperidol-sensitized Cebus monkeys. Initial examination of a few close cogeners of 1 enhanced confidence in the Cebus model as a predictor of dyskinetic potential. Considering dibenzazepines, 2 was not dyskinetic whereas 2a was dyskinetic. Among dibenzodiazepines, 1 did not induce dyskinesias where as its N-2-(2-hydroxyethoxy)ethyl analogue 3 was dyskinetic. The emergence of such distinctions presented an opportunity. Thus, aromatic and N-substituted analogues of 6-(piperazin-1-yl)-11H-dibenz[b,e]azepines and 11-(piperazin-1-yl)dibenzo[b,f][1,4]thiazepines and -oxazepines were prepared and evaluated. 11-(4-[2-(2-Hydroxyethoxy)ethyl]piperazin-1-yl)dibenzo[b,f][1,4]thiazepine (23) was found to be an apomorphine antagonist comparable to clozapine. It was essentially nondyskinetic in the Cebus model. With 23 as a platform, a number of N-substituted analogues were found to be good apomorphine antagonists but all were dyskinetic.

  DOI：

  10.1021/jm000242+
• 作为产物：
  描述：

  2-(Toluene-4-sulfonylamino)-benzoyl chloride 在 氢氧化钾 、 PPA 、 硫酸 、 四氯化锡 、 一水合肼 作用下， 以 二硫化碳 、 甲苯 、 二乙二醇 为溶剂， 反应 9.5h， 生成 5,10-dihydro-4H-thieno<3,2-c><1>benzazepin-4-one
  参考文献：
  名称：

  Hunziker; Fischer; Kipfer, European Journal of Medicinal Chemistry, 1981, vol. 16, # 5, p. 391 - 398

  摘要：

  DOI：

文献信息

• Process for making 11-piperazino-diazepines, oxazepines, thiazepines and
  申请人：Sandoz, Inc.

  公开号：US03962248A1

  公开（公告）日：1976-06-08

  This invention concerns a novel process for the preparation of 6-piperazinyl derivatives of morphantridine and corresponding ring-substituted and hereto analogues thereof, comprising reacting a compound of the formula: ##SPC1## Wherein A is benzene or thiophene, and X is --CH.sub.2 -- or a hetero atom or group, with a complex comprising titanium, zirconium, hafnium or vanadium and a corresponding piperazinyl derivative. The end products are in general known and useful as neuroleptics.

  这项发明涉及一种新颖的制备6-哌嗪基吗啡三啶及其对应的环取代和对应的类似物的方法，包括将具有以下结构的化合物与含有钛、锆、铪或钒的复合物以及相应的哌嗪基衍生物反应：##SPC1## 其中A为苯或噻吩，X为--CH.sub.2--或杂原子或基团。最终产物通常为已知的神经阻滞剂，并具有实用价值。
• HUNZIKER, F.;FISCHER, R.;KIPFER, P.;SCHMUTZ, J.;BUERKI, H. R.;FICHENBERGE+, EUR. J. MED. CHEM.-CHIM. THER., 1981, 16, N 5, 391-398
  作者：HUNZIKER, F.、FISCHER, R.、KIPFER, P.、SCHMUTZ, J.、BUERKI, H. R.、FICHENBERGE+

  DOI：——

  日期：——
• US3962248A
  申请人：——

  公开号：US3962248A

  公开（公告）日：1976-06-08
• Hunziker; Fischer; Kipfer, European Journal of Medicinal Chemistry, 1981, vol. 16, # 5, p. 391 - 398
  作者：Hunziker、Fischer、Kipfer、et al.

  DOI：——

  日期：——
• Behavioral Approach to Nondyskinetic Dopamine Antagonists:  Identification of Seroquel
  作者：Edward J. Warawa、Bernard M. Migler、Cyrus J. Ohnmacht、Ann L. Needles、George C. Gatos、Frances M. McLaren、Cynthia L. Nelson、Karen M. Kirkland

  DOI：10.1021/jm000242+

  日期：2001.2.1

  A great need exists for antipsychotic drugs which will not induce extrapyramidal symptoms (EPS) and tardive dyskinesias (TDs). These side effects are deemed to be a consequence of nonselective blockade of nigrostriatal and mesolimbic dopamine D2 receptors. Nondyskinetic clozapine (1) is a low-potency D2 dopamine receptor antagonist which appears to act selectively in the mesolimbic area. In this work dopamine antagonism was assessed in two mouse behavioral assays: antagonism of apomorphine-induced climbing and antagonism of apomorphine-induced disruption of swimming. The potential for the liability of dyskinesias was determined in haloperidol-sensitized Cebus monkeys. Initial examination of a few close cogeners of 1 enhanced confidence in the Cebus model as a predictor of dyskinetic potential. Considering dibenzazepines, 2 was not dyskinetic whereas 2a was dyskinetic. Among dibenzodiazepines, 1 did not induce dyskinesias where as its N-2-(2-hydroxyethoxy)ethyl analogue 3 was dyskinetic. The emergence of such distinctions presented an opportunity. Thus, aromatic and N-substituted analogues of 6-(piperazin-1-yl)-11H-dibenz[b,e]azepines and 11-(piperazin-1-yl)dibenzo[b,f][1,4]thiazepines and -oxazepines were prepared and evaluated. 11-(4-[2-(2-Hydroxyethoxy)ethyl]piperazin-1-yl)dibenzo[b,f][1,4]thiazepine (23) was found to be an apomorphine antagonist comparable to clozapine. It was essentially nondyskinetic in the Cebus model. With 23 as a platform, a number of N-substituted analogues were found to be good apomorphine antagonists but all were dyskinetic.