4-<4-(1,2-benzisoxazol-3-yl)-1-piperazinyl>-1-(4-fluorophenyl)-1-butanone | 87692-12-4

• 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
• 英文别名: 4-(4-Benzo[d]isoxazol-3-yl-piperazin-1-yl)-1-(4-fluoro-phenyl)-butan-1-one；4-[4-(1,2-benzoxazol-3-yl)piperazin-1-yl]-1-(4-fluorophenyl)butan-1-one
• CAS: 87692-12-4
• 化学式: C₂₁H₂₂FN₃O₂
• 分子量: 367.423
• InChiKey: DRWPDXAVBOPONN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  27
• 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：
  0
• 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 在 sodium tetrahydroborate 作用下， 以 乙醇 为溶剂， 反应 20.0h， 以35%的产率得到α-<3-<4-(1,2-benzisoxazol-3-yl)-1-piperazinyl>propyl>-4-fluorobenzenemethanol
  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：

  3-哌嗪-1,2-苯异唑 、 4-(3-Chloropropyl)-4-(4-fluorophenyl)-1,3-dioxolane 、 potassium carbonate 以25%的产率得到
  参考文献：
  名称：

  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

  摘要：

  DOI：

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.
• 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：——