3-[4-(4-Benzo[d]isoxazol-3-yl-[1,4]diazepan-1-yl)-butyl]-1-thia-3-aza-spiro[4.4]nonane-2,4-dione | 99748-53-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并异恶唑
• 英文名称: 3-[4-(4-Benzo[d]isoxazol-3-yl-[1,4]diazepan-1-yl)-butyl]-1-thia-3-aza-spiro[4.4]nonane-2,4-dione
• 英文别名: 3-[4-[4-(1,2-benzoxazol-3-yl)-1,4-diazepan-1-yl]butyl]-1-thia-3-azaspiro[4.4]nonane-2,4-dione
• CAS: 99748-53-5
• 化学式: C₂₃H₃₀N₄O₃S
• 分子量: 442.582
• InChiKey: FOWNWEAIIITWBW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  95.2
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  水杨基羟肟酸 在 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 、 乙腈 为溶剂， 反应 60.0h， 生成 3-[4-(4-Benzo[d]isoxazol-3-yl-[1,4]diazepan-1-yl)-butyl]-1-thia-3-aza-spiro[4.4]nonane-2,4-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

文献信息

• 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：——
• 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.