8-(1,2-benzisothiazol-3-yl)-8-aza-5-azoniaspiro[4.5]decane bromide | 87691-94-9

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 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: 8-(1,2-benzisothiazol-3-yl)-8-aza-5-azoniaspiro[4.5]decane bromide
• 英文别名: 3-(8-aza-5-azoniaspiro[4.5]decan-8-yl)-1,2-benzothiazole;bromide
• CAS: 87691-94-9
• 化学式: Br*C₁₅H₂₀N₃S
• 分子量: 354.314
• InChiKey: DEODAGRVBBQKJJ-UHFFFAOYSA-M

物化性质

• 熔点：
  258-259 °C

计算性质

• 辛醇/水分配系数(LogP)：
  -0.27
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  44.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3,3-四亚甲基戊二酰亚胺 、 8-(1,2-benzisothiazol-3-yl)-8-aza-5-azoniaspiro[4.5]decane bromide 在 18-冠醚-6 、 potassium carbonate 作用下， 以 甲苯 为溶剂， 反应 22.0h， 以88%的产率得到替螺酮
  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-chlorosulfenylbenzoyl chloride 在 ammonium hydroxide 、 18-冠醚-6 、 potassium carbonate 、 三氯氧磷 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 52.5h， 生成 8-(1,2-benzisothiazol-3-yl)-8-aza-5-azoniaspiro[4.5]decane bromide
  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

• Cyclic Benzamides as Mixed Dopamine D2/Serotonin 5-HT2 Receptor Antagonists: Potential Atypical Antipsychotic Agents
  作者：Mark H. Norman、Greg C. Rigdon、Frank Navas、Barrett R. Cooper

  DOI：10.1021/jm00042a008

  日期：1994.8

  A series of novel 4-(4-(1,2-benzisothiazol-3-yl)-1-piperazinyl)butyl) cyclic amides was prepared and evaluated as potential antipsychotic agents. The target compounds were examined in vitro for their binding affinities to the dopamine D2, serotonin 5-HT2, and serotonin 5-HT1a receptors and in vivo for their ability to antagonize the apomorphine-induced climbing response in mice. Derivatives that exhibited

  制备了一系列新颖的4-（4-（1,2-苯并噻唑-3-基）-1-哌嗪基）丁基）环酰胺，并将其评估为潜在的抗精神病药。在体外检查靶标化合物与多巴胺D2、5-羟色胺5-HT2和5-羟色胺5-HT1a受体的结合亲和力，并在体内拮抗阿朴吗啡诱导的小鼠爬升反应的能力。选择在体外表现出良好的D2 / 5-HT2选择性和在体内具有良好效能的衍生物，以在旨在评估其潜在锥体外系副作用的测试中进行进一步评估。本文讨论的结构修饰着眼于双环酰胺亚基，导致制备各种杂环系统（即邻苯二甲酰亚胺，异吲哚啉酮，异喹啉酮，苯并ze庚酮，吲唑酮，酞嗪酮，4-甲基酞嗪酮，1,1-二甲基苯并异噻唑酮，苯并三嗪酮，高邻苯二甲酰亚胺，苯并异噻唑酮，邻苯二嗪二酮，喹唑啉和饱和邻苯二氮酮。发现该系列中的效力和选择性取决于环的大小，共价连接单元的性质，官能团的相对位置，不饱和度和相对立体化学。通常，在这项研究中检查的环状苯甲酰胺表现出受体结合
• 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.

  本文披露了二取代N，N-哌嗪基衍生物，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]十二酮，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物。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]十二烷-7,9-二酮是具有选择性抗精神病活性的典型实施例。
• Analogues of the potential antipsychotic agent 1192U90: amide modifications
  作者：Frank Navas III、Flora L.M. Tang、Lee T. Schaller、Mark H. Norman

  DOI：10.1016/s0968-0896(98)00041-8

  日期：1998.6

  Analogues of 2-amino-N-(4-(4-(1, 2-benzisothiazol-3 -yl)-1-piperazinyl)-butyl)benzamide hydrochloride (1192U90) were prepared and evaluated in receptor binding assays for the dopamine D-2, serotonin 5-HT1a, and serotonin 5-HT2 receptors. Eight compounds have been synthesized in which the amide group of 1192U90 has been replaced with a variety of functional groups (i.e, ester, ketone, thioamide, butyramide, butyranilide, sulfonamide, alkoxyamide and hydrazide). These compounds exhibited moderate to potent affinities (0.55-200 nM) for all three receptors. Several analogues exhibited improved selectivity for the 5-HT2 receptor with D-2/5-HT2 binding ratios greater than 1192U90. (C) 1998 Elsevier Science Ltd. All rights reserved.
• J. Med. Chem. 1986, 29, 359-369
  作者：

  DOI：——

  日期：——
• YEVICH, J. P.;NEW, J. S.;SMITH, D. W.;LOBECK, W. G.;CATT, J. D.;MINIELLI,+, J. MED. CHEM., 1986, 29, N 3, 359-369
  作者：YEVICH, J. P.、NEW, J. S.、SMITH, D. W.、LOBECK, W. G.、CATT, J. D.、MINIELLI,+

  DOI：——

  日期：——