7-HydroxyQuetiapineAcetate | 329217-62-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并硫氮卓类
• 英文名称: 7-HydroxyQuetiapineAcetate
• 英文别名: 2-[2-[4-(2-hydroxybenzo[b][1,4]benzothiazepin-6-yl)piperazin-1-yl]ethoxy]ethyl acetate
• CAS: 329217-62-1
• 化学式: C₂₃H₂₇N₃O₄S
• 分子量: 441.551
• InChiKey: WYWODQNHXCBWLV-UHFFFAOYSA-N

物化性质

• 沸点：
  618.5±65.0 °C(Predicted)
• 密度：
  1.31±0.1 g/cm3(Predicted)
• 溶解度：
  甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  99.9
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  7-HydroxyQuetiapineAcetate 在 氢氧化钾 作用下， 以 甲醇 为溶剂， 反应 4.0h， 生成 7-羟基 喹硫平杂质
  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：

  1-[2-(2-羟基乙氧基)乙基]哌嗪 在 氢溴酸 作用下， 以 xylene 为溶剂， 反应 19.0h， 生成 7-HydroxyQuetiapineAcetate
  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

• FATTY ACID CONJUGATES OF QUETIAPINE, PROCESS FOR MAKING AND USING THE SAME
  申请人：KemPharm, Inc.

  公开号：US20170247368A1

  公开（公告）日：2017-08-31

  The presently described technology provides a novel class of prodrugs of quetiapine that can be synthesized by chemically conjugating fatty acids to quetiapine. Pharmaceutical compositions and methods of synthesizing conjugates of the present technology are also provided. Methods of treating patients with the compositions of the present technology are also provided.

  目前所描述的技术提供了一种新型的奎硫平前药类，可以通过将脂肪酸与奎硫平进行化学共轭来合成。同时，还提供了制备本技术共轭物的药物组合物和方法。还提供了使用本技术组合物治疗患者的方法。
• Fatty Acid Conjugates of Quetiapine, Process for Making and Using the Same
  申请人：Mickle Travis

  公开号：US20110223207A1

  公开（公告）日：2011-09-15

  The presently described technology provides a novel class of prodrugs of quetiapine that can be synthesized by chemically conjugating fatty acids to quetiapine. Pharmaceutical compositions and methods of synthesizing conjugates of the present technology are also provided. Methods of treating patients with the compositions of the present technology are also provided.
• US8900604B2
  申请人：——

  公开号：US8900604B2

  公开（公告）日：2014-12-02
• US9511149B2
  申请人：——

  公开号：US9511149B2

  公开（公告）日：2016-12-06
• US9889198B2
  申请人：——

  公开号：US9889198B2

  公开（公告）日：2018-02-13