3-(1-piperazinyl)-2,1-benzisothiazole | 87757-03-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 3-(1-piperazinyl)-2,1-benzisothiazole
• 英文别名: 1-(1,2-benzoisothiazol-3-yl)-piperazine；3-piperazin-1-yl-2,1-benzothiazole
• CAS: 87757-03-7
• 化学式: C₁₁H₁₃N₃S
• 分子量: 219.31
• InChiKey: MPXJNSAEPJKLBY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  56.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  8-(4-氯丁基)-8-氮杂螺[4.5]癸烷-7,9-二酮 、 3-(1-piperazinyl)-2,1-benzisothiazole 在 potassium carbonate 、 potassium iodide 作用下， 以 乙腈 为溶剂， 反应 20.0h， 生成 8-[4-[4-(2,1-Benzisothiazol-3-yl)-1-piperazinyl]butyl]-8-azaspiro[4.5]decane-7,9-dione
  参考文献：
  名称：

  Synthesis and biological evaluation of 1-(1,2-benzisothiazol-3-yl)- and (1,2-benzisoxazol-3-yl)piperazine derivatives as potential antipsychotic agents

  摘要：

  Members of the series of title compounds were tested for potential antipsychotic activity in relevant receptor binding assays and behavioral screens. Structure-activity relationships within the series are discussed. Compound 24 (BMY 13859-1), a (1,2-benzisothiazol-3-yl)piperazine derivative, was selected for further study because of its potent and selective profile in primary CNS tests. It was active in the Sidman avoidance paradigm and blocked amphetamine-induced stereotyped behavior in dogs for up to 7 h. The compound's lack of typical neuroleptic-like effects in the rat catalepsy test and its failure to produce dopamine receptor supersensitivity following chronic administration indicate that it should not cause the movement disorders commonly associated with antipsychotic therapy. Although 24 has potent affinity for dopaminergic binding sites, its even greater affinity for serotonin receptors suggests that a serotonergic component may be relevant to its atypical profile. Compound 24 is currently undergoing clinical evaluation in schizophrenic patients.

  DOI：

  10.1021/jm00153a010
• 作为产物：
  描述：

  2,1-Benzisothiazolin-3-on 在 吡啶 、 三氯氧磷 作用下， 反应 24.0h， 生成 3-(1-piperazinyl)-2,1-benzisothiazole
  参考文献：
  名称：

  Synthesis and biological evaluation of 1-(1,2-benzisothiazol-3-yl)- and (1,2-benzisoxazol-3-yl)piperazine derivatives as potential antipsychotic agents

  摘要：

  Members of the series of title compounds were tested for potential antipsychotic activity in relevant receptor binding assays and behavioral screens. Structure-activity relationships within the series are discussed. Compound 24 (BMY 13859-1), a (1,2-benzisothiazol-3-yl)piperazine derivative, was selected for further study because of its potent and selective profile in primary CNS tests. It was active in the Sidman avoidance paradigm and blocked amphetamine-induced stereotyped behavior in dogs for up to 7 h. The compound's lack of typical neuroleptic-like effects in the rat catalepsy test and its failure to produce dopamine receptor supersensitivity following chronic administration indicate that it should not cause the movement disorders commonly associated with antipsychotic therapy. Although 24 has potent affinity for dopaminergic binding sites, its even greater affinity for serotonin receptors suggests that a serotonergic component may be relevant to its atypical profile. Compound 24 is currently undergoing clinical evaluation in schizophrenic patients.

  DOI：

  10.1021/jm00153a010

文献信息

• [EN] AN IMPROVED PROCESS FOR THE PREPARATION OF LURASIDONE HYDROCHLORIDE<br/>[FR] PROCÉDÉ AMÉLIORÉ DE PRÉPARATION DE CHLORHYDRATE DE LURASIDONE
  申请人：JUBILANT GENERICS LTD FORMERLY JUBILANT LIFE SCIENCES DIVISION

  公开号：WO2016059649A1

  公开（公告）日：2016-04-21

  Disclosed herein is an improved process for the preparation of Lurasidone and its pharmaceutically acceptable salts via novel intermediate and use thereof for the preparation of an antipsychotic agent useful for the treatment of schizophrenia and bipolar disorder. Further, present invention provides a cost effective and eco-friendly process for producing Lurasidone hydrochloride of formula (I) substantially free of residual solvent(s) at industrial scale.

  本文披露了一种改进的工艺，通过新颖的中间体及其用途，用于制备Lurasidone及其药用可接受盐，用于制备一种抗精神分裂症和双相情感障碍治疗有用的抗精神病药物。此外，本发明提供了一种成本效益和环保的工艺，用于在工业规模上生产几乎不含残留溶剂的盐酸Lurasidone（化学式（I））。
• [EN] NOVEL POLYMORPH OF LURASIDONE HYDROCHLORIDE<br/>[FR] NOUVEAU POLYMORPHE DE CHLORHYDRATE DE LURASIDONE
  申请人：HETERO RESEARCH FOUNDATION

  公开号：WO2013132511A1

  公开（公告）日：2013-09-12

  The present invention provides a novel amorphous Form of lurasidone hydrochloride, process for its preparation and pharmaceutical compositions comprising it. In one aspect, the present invention provides an amorphous form of lurasidone hydrochloride. In another aspect, the present invention provides a process for the preparation of lurasidone hydrochloride amorphous Form, which comprises: a) dissolving lurasidone hydrochloride in a mixture of alcoholic solvent and water; and b) subjecting the resulting solution to lyophilization to obtain lurasidone hydrochloride amorphous form.

  本发明提供了一种新型的盐酸卢拉西酮无定形形式，以及其制备方法和包括它的药物组合物。在一个方面，本发明提供了盐酸卢拉西酮的无定形形式。在另一个方面，本发明提供了一种制备盐酸卢拉西酮无定形形式的方法，包括：a)将盐酸卢拉西酮溶解在醇溶剂和水的混合物中；b)将所得溶液经过冻干处理，以获得盐酸卢拉西酮无定形形式。
• [EN] PROCESS FOR PURIFICATION OF ZIPRASIDONE<br/>[FR] PROCÉDÉ POUR LA PURIFICATION DE ZIPRASIDONE
  申请人：HETERO RESEARCH FOUNDATION

  公开号：WO2011080749A1

  公开（公告）日：2011-07-07

  The present invention relates to a process for the preparation of pure ziprasidone. Thus, for example, ziprasidone tosylate was added to water and aqueous ammonia at room temperature, the contents were heated to 65 °C and maintained for 30 minutes, filtered, washed with water to obtain a wet solid, tetrahydrofuran was added to wet solid and maintained at reflux for 30 minutes. The separated solid was filtered and dried at 65 °C to obtain pure ziprasidone.

  本发明涉及一种制备纯Ziprasidone的方法。例如，将Ziprasidone Tosylate加入水和水合氨，在室温下加热到65℃并保持30分钟，过滤，用水洗涤以得到湿固体，将四氢呋喃加入湿固体并在回流下保持30分钟。分离得到的固体经过滤和在65℃下干燥，得到纯Ziprasidone。
• Benzisothiazole and benzisoxazole piperazine derivatives
  申请人：Mead Johnson & Company

  公开号：US04411901A1

  公开（公告）日：1983-10-25

  Disubstituted N,N-piperazinyl derivatives are disclosed wherein one substituent is benzisothiazol-3-yl or benzisoxazol-3-yl and the other is alkylene attached to heterocycles such as azaspiro[4.5]decanedione, dialkylglutarimide, thiazolidinedione and spirocyclopentylthiazolidinedione or butyrophenone-like groups. The compounds have psychotropic properties and 8-[4-[4-(1,2-benzisothiazol-3-yl)-1-piperazinyl]butyl]-8-azaspior[4.5]deca ne-7,9-dione is a typical embodiment having selective antipsychotic activity.

  本发明公开了二取代的N，N-哌嗪衍生物，其中一个取代基是苯并异噻唑-3-基或苯并异恶唑-3-基，另一个取代基是连接到杂环上的烷基，例如氮杂螺[4.5]癸二酮，二烷基谷氨酰胺，噻唑烷二酮和螺环戊基噻唑烷二酮或丁酰苯酮类似的基团。这些化合物具有精神药理学性质，8-[4-[4-(1,2-苯并异噻唑-3-基)-1-哌嗪基]丁基]-8-氮杂螺[4.5]癸-7,9-二酮是一种具有选择性抗精神病活性的典型实施例。
• [EN] AN IMPROVED PROCESS FOR THE PREPARATION OF LURASIDONE AND ITS INTERMEDIATE<br/>[FR] PROCÉDÉ AMÉLIORÉ DE PRÉPARATION DE LURASIDONE ET DE SES INTERMÉDIAIRES
  申请人：PIRAMAL ENTPR LTD

  公开号：WO2016110798A1

  公开（公告）日：2016-07-14

  The present invention provides an improved process for preparation of the substantially pure (3a R,7a R)-4'-(benzo[d]isothiazol-3-yl)octahydrospiro[isoindole-2,1'-piperazin]-1'-ium methanesulfonate (referred to as compound-II), which is useful as a key intermediate for the synthesis of lurasidone ((3a R,4S,7R,7a S)-2-(1R,2R)-2-[4-(1,2-benzisothiazol-3- yl)piperazin-1ylmethyl] cyclohexylmethyl}hexahydro-4,7-methano-2H-isoindole-1,3-dione). The process comprises reaction of the compound-III (as described herein) with the compound-IV (as described herein) in the presence of a solvent mixture selected from an alcohol and water; and a base The improved process for the preparation of compound II provides the product with total amount of unreacted compound-IV as impurity in less than 0.06 % and the product with HPLC purity as ≥ 99.8%. The process further refers purification of Lurasidone hydrochloride, wherein the product contains the residual acetone < 5000 ppm.

  本发明提供了一种改进的制备过程，用于制备几乎纯的(3aR,7aR)-4'-(苯并[d]异噻唑-3-基)八氢螺[异吲哚-2,1'-哌嗪]-1'-甲磺酸盐（称为化合物II），该化合物是合成卢拉西酮的关键中间体（（3aR，4S，7R，7aS）-2-（1R，2R）-2-[4-(1,2-苯并异噻唑-3-基)哌嗪-1-基甲基]环己基甲基}六氢-4,7-甲基-2H-异吲哚-1,3-二酮）。该过程包括将化合物III（如本文所述）与化合物IV（如本文所述）在醇和水的溶剂混合物和碱的存在下反应；改进的制备化合物II的过程可在不到0.06％的未反应化合物IV总量的情况下提供产品，并且产品的HPLC纯度为≥99.8％。该过程还涉及卢拉西酮盐酸盐的纯化，其中产品中残留的丙酮<5000 ppm。