11-(4-[2-(2-hydroxyethoxy)ethyl]-1-piperazinyl)dibenzo[b,f]-1,4-thiazepine hydrochloride | 930086-71-8

• 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: 11-(4-[2-(2-hydroxyethoxy)ethyl]-1-piperazinyl)dibenzo[b,f]-1,4-thiazepine hydrochloride
• 英文别名: quetiapine hydrochloride；2-[2-(4-benzo[b][1,4]benzothiazepin-6-ylpiperazin-1-yl)ethoxy]ethanol;hydrochloride
• CAS: 930086-71-8
• 化学式: C₂₁H₂₅N₃O₂S*ClH
• 分子量: 419.975
• InChiKey: ABVUAVNQKKGGEU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.28
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  73.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  11-(4-[2-(2-hydroxyethoxy)ethyl]-1-piperazinyl)dibenzo[b,f]-1,4-thiazepine hydrochloride 在 sodium periodate 作用下， 反应 22.0h， 以1.98 g的产率得到喹硫平亚砜
  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：

  富马酸喹硫平 在 氨 、 盐酸 作用下， 以 水 、 乙酸乙酯 、 异丙醇 为溶剂， 反应 1.0h， 生成 11-(4-[2-(2-hydroxyethoxy)ethyl]-1-piperazinyl)dibenzo[b,f]-1,4-thiazepine hydrochloride
  参考文献：
  名称：

  POLYMORPHIC FORMS OF QUETIAPINE

  摘要：

  本发明涉及制备喹硫平盐的多形态过程。更具体地，涉及制备喹硫平盐的多形态，包括A、B和C形态的制备。本发明还涉及包含A、B和C形态的制剂，以及将该制剂用于治疗精神分裂症、与双相I型障碍相关的急性躁狂发作的用途。本发明还涉及制备喹硫平草酸盐和马来酸盐。

  公开号：

  US20070072840A1

文献信息

• PROCESS FOR PREPARING QUETIAPINE AND QUETIAPINE FUMARATE
  申请人：Bosch I Llado Jordi

  公开号：US20090076262A1

  公开（公告）日：2009-03-19

  The invention comprises a process for preparing quetiapine and/or its salts, including, quetiapine fumarate. The process generally comprises reacting dibenzothiazepinone (dibenzo[bf][1,4]thiazepin-11(10H)-one) with phosphorous oxychloride in the presence of triethylamine in an aromatic organic solvent such as toluene or, preferably, xylene at reflux temperature to obtain an aromatic hydrocarbon solution of 11-chloro-dibenzo[bf][1,4]thiazepine. Thereafter, the 11-chloro-dibenzo[bf][1,4]thiazepine is reacted with 2-(2-piperazin-1-ylethoxy)-ethanol to yield, following several processing steps, quetiapine. Compound I can then be further reacted with fumaric acid at elevated temperature to yield quetiapine fumarate. The resulting quetiapine fumarate obtained is suitable for use in pharmaceutical preparations.

  该发明涉及一种制备喹硫平及/或其盐的过程，包括喹硫平富马酸盐。该过程通常包括在芳香有机溶剂（如甲苯或更好的二甲苯）中，在回流温度下，将二苯并噻吩酮（二苯并[bf][1,4]噻吩-11(10H)-酮）与三乙胺的存在下与氯化亚磷酸酯反应，以获得11-氯二苯并[bf][1,4]噻吩的芳香烃溶液。随后，将11-氯二苯并[bf][1,4]噻吩与2-(2-哌嗪-1-基乙氧基)-乙醇反应，经过几个处理步骤，得到喹硫平。化合物I随后可以在高温下与富马酸反应，生成喹硫平富马酸盐。获得的喹硫平富马酸盐适用于制药制剂中的使用。
• QUETIAPINE SALTS AND THEIR POLYMORPHS
  申请人：Dixit Girish

  公开号：US20100278878A1

  公开（公告）日：2010-11-04

  The present invention relates to novel and stable salt forms of quetiapine, processes for preparation, pharmaceutical compositions, and method of treating thereof. More particularly, the present invention provides novel acid addition salts of quetiapine wherein the acid counter ion is provided by an acid selected from the group consisting of benzene sulfonic acid, dibenzoyl-L-(+)-tartaric acid and di-p-toluoyl-L-(+)-tartaric acid. The present invention also provides novel polymorphic forms of quetiapine salts selected from the group consisting of quetiapine hydrobromide, quetiapine sulfate, quetiapine nitrate and quetiapine citrate.

  本发明涉及quetiapine的新型和稳定盐形式、制备方法、制药组合物以及其治疗方法。更具体地，本发明提供了quetiapine的新型酸加成盐，其中酸对离子由苯磺酸、二苯乙酰-L-(+)-酒石酸和二-p-甲苯酰-L-(+)-酒石酸中的一种提供。本发明还提供了quetiapine盐的新型多形式，所述多形式选自quetiapine羟溴酸盐、quetiapine硫酸盐、quetiapine硝酸盐和quetiapine柠檬酸盐。
• 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。
• Quetiapine hemifumarate purification by crystallization
  申请人：Fermion Oy

  公开号：US08044039B2

  公开（公告）日：2011-10-25

  The present invention relates to a process for preparing and purifying crystalline quetiapine hemifumarate, which comprises preparing crystalline quetiapine hemifumarate via a crystalline salt, which is not a salt of fumaric acid.

  本发明涉及一种制备和纯化晶体盐酸喹硫平半富马酸盐的方法，包括通过一种非富马酸盐的晶体盐制备晶体盐酸喹硫平半富马酸盐。
• Quetiapine Hemifumarate Purification by Crystallization
  申请人：Grumann Arme

  公开号：US20090156802A1

  公开（公告）日：2009-06-18

  The present invention relates to a process for preparing and purifying crystalline quetiapine hemifumarate, which comprises preparing crystalline quetiapine hemifumarate via a crystalline salt, which is not a salt of fumaric acid.

  本发明涉及一种制备和纯化晶体盐酸喹硫平的方法，包括通过一种非富马酸盐的晶体盐制备晶体盐酸喹硫平。