2-[2-(4-benzo[b][1,4]benzothiazepin-6-ylpiperazin-1-yl)ethoxy]ethanol;but-2-enedioate;hydron

• 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: 2-[2-(4-benzo[b][1,4]benzothiazepin-6-ylpiperazin-1-yl)ethoxy]ethanol;but-2-enedioate;hydron
• 化学式: C46H54N6O8S2
• 分子量: 883.1
• InChiKey: ZTHJULTYCAQOIJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.42
• 重原子数：
  62
• 可旋转键数：
  14
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  222
• 氢给体数：
  4
• 氢受体数：
  14

文献信息

• [EN] COMPOSITIONS AND METHODS FOR TREATING CNS DISORDERS<br/>[FR] COMPOSITIONS ET MÉTHODES DE TRAITEMENT DE TROUBLES DU SYSTÈME NERVEUX CENTRAL
  申请人：SAGE THERAPEUTICS INC

  公开号：WO2020264495A1

  公开（公告）日：2020-12-30

  Provided herein is a compound of Formula (1-I): or a pharmaceutically acceptable salt thereof, wherein R2a, R2b, R3, R4a, R4b, R5, R6a, R6b, R11a, R11b, R16a, R16b, R19, R18, X, q, r, s, t, u, and n are defined herein. Also provided herein are pharmaceutical compositions comprising a compound of Formula (1-I) and methods of using the compounds, e.g, in the treatment of CNS -related disorders.

  本文提供的是Formula（1-I）的化合物或其药学上可接受的盐，其中R2a、R2b、R3、R4a、R4b、R5、R6a、R6b、R11a、R11b、R16a、R16b、R19、R18、X、q、r、s、t、u和n在此定义。本文还提供了包含Formula（1-I）化合物的药物组合物及使用这些化合物的方法，例如用于治疗与中枢神经系统相关的疾病。
• [EN] PROCESS FOR PRODUCING 11-[4-[2-(2-HYDROXYETHOXY)ETHYL]-1-PIPERAZINYL]DIBENZO[b,f][1,4]THIAZEPINE AND A PHARMACEUTICALLY ACCEPTABLE SALT THEREOF<br/>[FR] PROCEDE DE PRODUCTION DE 11-[4-[2-(2-HYDROXYETHOXY)ETHYL]-1-PIPERAZINYL]DIBENZO[B,F][1,4]THIAZEPINE ET D'UN SEL ACCEPTABLE SUR LE PLAN PHARMACEUTIQUE ASSOCIE
  申请人：JUBILANT ORGANOSYS LTD

  公开号：WO2006027789A1

  公开（公告）日：2006-03-16

  A process for producing 11-[4-[2-(2-hydroxyethoxy)ethyl]-l-piperazinyl]dibenzo [b,f][1,4]thiazepine [I] and a pharmaceutically suitable acid addition salt is disclosed. Accordingly, thiosalicylic acid [XVI] is reacted with o-halonitrobenzene [XVII] using a phase transfer catalyst to obtain 2-nitro-2'-carboxydiphenylsulphide [XI]. It is hydrogenated in the presence of a noble metal catalyst to obtain 2-amino-2' carboxydiphenyl sulphide [X]. The 2-amino-2'-carboxydiphenylsulphide [X] is reacted with halide or oxyhalide of the phosphorous to obtain in situ iminohalide [VI], which further reacts as such with 1-hydroxyethoxyethylpiperazine or condenses with piperazine to obtain 11-piperazinyldi.benzo[b,f][1,4]thiazepine [XIX] which further reacts with 2- chloroethoxyethanol or reacts with 1-(2-hydroxyethyl)piperazine to give 11-[4-(2-hydroxyethyl)piperazine-1-yl]dibenzo[b,f][ 1,4]thiazepine [XXXI] which further converts to an intermediate 11-[4-(2-substitutedethyl)piperazin-1- yl)dibenzo[b,f][1,4]thiazepine wherein the substituent at the 2-position is selected from mesyloxy or tosyloxy or halo group [XXXII] followed by reaction with ethylene glycol to give quetiapine [1].

  揭示了一种生产11-[4-[2-(2-羟基乙氧基)乙基]-1-哌嗪基]二苯并[b,f][1,4]噻吩[I]及其药用合适的酸盐的方法。因此，巯基水杨酸[XVI]与o-卤代硝基苯[XVII]在相转移催化剂的作用下反应，得到2-硝基-2'-羧基二苯硫醚[XI]。在贵金属催化剂的存在下加氢得到2-氨基-2'-羧基二苯硫醚[X]。2-氨基-2'-羧基二苯硫醚[X]与磷的卤代物或氧卤代物反应，得到原位亚胺卤化物[VI]，后者直接与1-羟乙氧乙基哌嗪反应或与哌嗪缩合，得到11-哌嗪二.苯并[b,f][1,4]噻吩[XIX]，它进一步与2-氯乙氧乙醇反应或与1-(2-羟乙基)哌嗪反应，得到11-[4-(2-羟乙基)哌嗪-1-基]二苯并[b,f][1,4]噻吩[XXXI]，它进一步转化为中间体11-[4-(2-取代乙基哌嗪-1-基)二苯并[b,f][1,4]噻吩，其中2-位置的取代基选择自mesyloxy或tosyloxy或卤素基[XXXII]，然后与乙二醇反应得到喹硫平[1]。
• [EN] PROCESS FOR THE SYNTHESIS OF QUETIAPINE<br/>[FR] PROCÉDÉ POUR LA SYNTHÈSE DE QUÉTIAPINE
  申请人：ITALIANA SINT SPA

  公开号：WO2010085976A1

  公开（公告）日：2010-08-05

  The present invention relates to a process for the synthesis of quetiapine. In particular, a process is provided for the synthesis of quetiapine of formula (A) comprising reacting dibenzo [b, f ] [1, 4] thiazepin- 11 (10H) -one, intermediate (I) with phosphorous oxychloride to give 11- chlorodibenzo [b, f ] [1, 4] thiazepine, intermediate (II) wherein the said reaction of intermediate (I) to intermediate (II) is performed in an organic solvent in the presence of a mixture of an organic base together with an inorganic base.

  本发明涉及一种合成喹硫平的方法。具体地，提供了一种合成式(A)中的喹硫平的方法，包括将二苯并[b, f][1,4]噻二氮杂环戊酮，中间体(I)与氯化亚磷反应，得到11-氯代二苯并[b, f][1,4]噻二氮杂环戊烷，中间体(II)，其中中间体(I)到中间体(II)的反应在有机溶剂中，在有机碱和无机碱的混合物的存在下进行。
• [EN] A PROCESS FOR THE PREPARATION OF QUETIAPINE<br/>[FR] PROCÉDÉ DE PRÉPARATION DE QUÉTIAPINE
  申请人：FERMION OY

  公开号：WO2009095529A1

  公开（公告）日：2009-08-06

  The invention relates to a method for the preparation of 11- (4- [2- (2- hydroxyethoxy) ethyl] -1-piperazinyl] dibenzo [b, f ] -1, 4-thiazepine and pharmaceutically acceptable salts thereof comprising the reaction of 1- [2- (hydroxyethoxy) -ethyl] piperazine with dibenzo [b, f] [1, 4] thiazepin-11-ylamine.

  本发明涉及一种制备11-（4-[2-（2-羟基乙氧基）乙基]-1-哌嗪基]二苯并[b，f] [1,4]噻唑及其药学上可接受的盐的方法，包括将1-[2-（羟基乙氧基）乙基]哌嗪与二苯并[b，f][1,4]噻唑-11-胺反应。
• 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。