4-<4-(1,2-benzisoxazol-3-yl)-1-piperazinyl>-1-(4-fluorophenyl)-1-butanone hydrochloride | 87692-13-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-<4-(1,2-benzisoxazol-3-yl)-1-piperazinyl>-1-(4-fluorophenyl)-1-butanone hydrochloride
• 英文别名: 4-[4-(1,2-benzisoxazol-3-yl)-1-piperazinyl]-1-(4-fluorophenyl)-1-butanone hydrochloride；4-[4-(1,2-benzoxazol-3-yl)piperazin-1-yl]-1-(4-fluorophenyl)butan-1-one;hydrochloride
• CAS: 87692-13-5
• 化学式: C₂₁H₂₂FN₃O₂*ClH
• 分子量: 403.884
• InChiKey: ADRGKMPOFKETQE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.17
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  49.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-<4-(1,2-benzisoxazol-3-yl)-1-piperazinyl>-1-(4-fluorophenyl)-1-butanone hydrochloride 在 sodium borohydrid 作用下， 以 乙醇 为溶剂， 生成 α-<3-<4-(1,2-benzisoxazol-3-yl)-1-piperazinyl>propyl>-4-fluorobenzenemethanol
  参考文献：
  名称：

  Benzisothiazole and benzisoxazole piperazine derivatives

  摘要：

  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。

  公开号：

  US04411901A1
• 作为产物：
  描述：

  水杨基羟肟酸 在 盐酸 、 potassium carbonate 、 三乙胺 、 N,N'-羰基二咪唑 、 potassium iodide 、 三氯氧磷 作用下， 以 四氢呋喃 、 乙醇 、 乙腈 为溶剂， 反应 60.25h， 生成 4-<4-(1,2-benzisoxazol-3-yl)-1-piperazinyl>-1-(4-fluorophenyl)-1-butanone hydrochloride
  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

• US4411901A
  申请人：——

  公开号：US4411901A

  公开（公告）日：1983-10-25
• US4452799A
  申请人：——

  公开号：US4452799A

  公开（公告）日：1984-06-05
• Synthesis and biological evaluation of 1-(1,2-benzisothiazol-3-yl)- and (1,2-benzisoxazol-3-yl)piperazine derivatives as potential antipsychotic agents
  作者：Joseph P. Yevich、James S. New、David W. Smith、Walter G. Lobeck、John D. Catt、Joseph L. Minielli、Michael S. Eison、Duncan P. Taylor、Leslie A. Riblet、Davis L. Temple

  DOI：10.1021/jm00153a010

  日期：1986.3

  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.
• 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。