8-chloro-10H-dibenzo[b,f][1,4]oxazepine-11-thione | 54584-84-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 8-chloro-10H-dibenzo[b,f][1,4]oxazepine-11-thione
• 英文别名: 8-chlorodibenzo[b,f]-1,4-oxazepin-11(10H)-thione；8-chlorodibenzo[b,f][1,4]oxazepine-11(10H)-thione；3-chloro-5H-benzo[b][1,4]benzoxazepine-6-thione
• CAS: 54584-84-8
• 化学式: C₁₃H₈ClNOS
• 分子量: 261.732
• InChiKey: RPVZBYDSOOJWSR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  17
• 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：
  53.4
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  8-chloro-10H-dibenzo[b,f][1,4]oxazepine-11-thione 在 氢氧化钾 、 溶剂黄146 作用下， 以 1,4-二氧六环 、 甲苯 为溶剂， 反应 23.67h， 生成 2-[2-[4-(3-Chlorobenzo[b][1,4]benzoxazepin-6-yl)piperazin-1-yl]ethoxy]ethanol
  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：

  8-chloro-10,11-dihydrodibenz[b,f][1,4]oxazepin-11-one 在 劳森试剂 作用下， 以 甲苯 为溶剂， 反应 1.5h， 生成 8-chloro-10H-dibenzo[b,f][1,4]oxazepine-11-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+

文献信息

• Tricyclic inhibitors of protein farnesyltransferase
  申请人：Warner Lambert Company

  公开号：US05919780A1

  公开（公告）日：1999-07-06

  Compounds of formula I ##STR1## wherein X is N or C--R.sup.9, Y is N--R.sup.10, CH.sub.2, O, S, SO, SO.sub.2, C.dbd.O or CH--OH, R is H or alkyl, R.sup.1 is heteroaryl, n is 1-5, and R.sup.2 -R.sup.10 are H or various substituents, are useful as inhibitors of protein farnesyl transferase and for the treatment of proliferative diseases including cancer, restenosis and psoriasis, and as antiviral agents.

  化学式I的化合物##STR1##其中X为N或C--R.sup.9，Y为N--R.sup.10，CH.sub.2，O，S，SO，SO.sub.2，C.dbd.O或CH--OH，R为H或烷基，R.sup.1为杂环烷基，n为1-5，R.sup.2-R.sup.10为H或各种取代基，可用作蛋白质法尼基转移酶的抑制剂，用于治疗包括癌症、再狭窄和牛皮癣在内的增殖性疾病，以及作为抗病毒剂。
• [EN] USE OF N-DESMETHYLCLOZAPINE AND RELATED COMPOUNDS AS DOPAMINE STABILIZING AGENTS<br/>[FR] UTILISATION DE N-DESMETHYLCLOZAPINE ET DE COMPOSES ASSOCIES COMME AGENTS STABILISATEURS DE DOPAMINE
  申请人：ACADIA PHARM INC

  公开号：WO2006107948A3

  公开（公告）日：2006-12-14
• Nagarajan,K.; Shah,R.K., Indian Journal of Chemistry, 1974, vol. 12, p. 263 - 269
  作者：Nagarajan,K.、Shah,R.K.

  DOI：——

  日期：——
• Nagarajan,K. et al., Indian Journal of Chemistry, 1974, vol. 12, p. 258 - 262
  作者：Nagarajan,K. 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.