3-哌嗪-1-基-1,2-苯并噻唑1-氧化物 | 128396-56-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 3-哌嗪-1-基-1,2-苯并噻唑1-氧化物
• 英文名称: 3-(1-piperazinyl)-1,2-benzisothiazole 1-oxide
• 英文别名: BMY 40729；Benzisothiazole sulphoxide；3-piperazin-1-yl-1,2-benzothiazole 1-oxide
• CAS: 128396-56-5
• 化学式: C₁₁H₁₃N₃OS
• 分子量: 235.31
• InChiKey: MOBIZCKXBZKGFC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  16
• 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：
  63.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-氟-2-硝基苯乙酸 、 3-哌嗪-1-基-1,2-苯并噻唑1-氧化物 在 双(2-氧代-3-恶唑烷基)次磷酰氯 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以50%的产率得到2-(5-Fluoro-2-nitro-phenyl)-1-[4-(1-oxo-1H-1λ4-benzo[d]isothiazol-3-yl)-piperazin-1-yl]-ethanone
  参考文献：
  名称：

  8-Substituted 3,4-dihydroquinolinones as a novel scaffold for atypical antipsychotic activity

  摘要：

  Several new, potent dopamine subtype 2 (DA D-2) active compounds with serotonin subtype 2A (5-HT2A) pharmacology are presented. 8-Substituted 3,4-dihydroquinolinones, tetrahydroquinolines, and N-acyl tetrahydroquinolines were evaluated in primary assays. Subtle changes on this novel scaffold translated to large changes in potency and selectivity in vitro. These compounds show promise as novel atypical antipsychotics for the treatment of schizophrenia. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.06.097
• 作为产物：
  描述：

  3-(1-哌嗪基)-1,2-苯并异噻唑 在 硫酸 、 硝酸 作用下， 以50%的产率得到3-哌嗪-1-基-1,2-苯并噻唑1-氧化物
  参考文献：
  名称：

  Synthesis and biological activity of the putative metabolites of the atypical antipsychotic agent tiospirone

  摘要：

  Putative oxidative metabolites of the lead antipsychotic agent tiospirone (1) were synthesized to assist in the identification of the authentic metabolic products found in human urine samples. Thus far, six authentic metabolites have been correlated to the synthetic species. 4a The putative metabolites were further examined in vitro to assess their central nervous system therapeutic potential. SAR analysis of these derivatives indicates that hydroxyl substitution, particularly in the azaspirodecanedione region of the molecule, diminishes the dopamine D-2 affinity of the species without significantly altering the serotonin type-1A and type-2 interactions. In addition, an increase in alpha-1-adrenergic affinity appears to be linked to the attenuation of effects at the dopamine receptors. The biological profile of the 6-hydroxytiospirone metabolite 42 was exemplary in these respects and the in vivo actions of this compound suggest potent antipsychotic potential with a minimal liability for extrapyramidal side effects (EPS). While compound 42 has been unambiguously characterized as an actual human metabolite of tiospirone, the role of 42 in the observed antipsychotic activity of the parent drug, if any, has not yet been determined.

  DOI：

  10.1021/jm00115a024

文献信息

• [EN] PIPERAZINE AND PIPERIDINE DERIVATIVES, AND THEIR USE AS ANTIPSYCHOTICS
  申请人：THE WELLCOME FOUNDATION LIMITED

  公开号：WO1993016073A1

  公开（公告）日：1993-08-19

  (EN) The present invention relates to a group of piperazine and piperidine derivatives, to processes for their preparation, to pharmaceutical compositions containing them and to their use in therapy, in particular in the treatment of psychotic disorders.(FR) La présente invention concerne un groupe de dérivés de pipérazine et de pipéridine, leurs procédés de préparation, des compositions pharmaceutiques les contenant et leur utilisation thérapeutique, notamment dans le traitement des maladies psychotiques.
• 8-Substituted 3,4-dihydroquinolinones as a novel scaffold for atypical antipsychotic activity
  作者：Jamie M. Singer、Bridget M. Barr、Linda L. Coughenour、Tracy F. Gregory、Michael A. Walters

  DOI：10.1016/j.bmcl.2005.06.097

  日期：2005.10

  Several new, potent dopamine subtype 2 (DA D-2) active compounds with serotonin subtype 2A (5-HT2A) pharmacology are presented. 8-Substituted 3,4-dihydroquinolinones, tetrahydroquinolines, and N-acyl tetrahydroquinolines were evaluated in primary assays. Subtle changes on this novel scaffold translated to large changes in potency and selectivity in vitro. These compounds show promise as novel atypical antipsychotics for the treatment of schizophrenia. (c) 2005 Elsevier Ltd. All rights reserved.
• Synthesis and biological activity of the putative metabolites of the atypical antipsychotic agent tiospirone
  作者：Joseph A. Cipollina、Edward H. Ruediger、James S. New、Mary E. Wire、Timothy A. Shepherd、David W. Smith、Joseph P. Yevich

  DOI：10.1021/jm00115a024

  日期：1991.11

  Putative oxidative metabolites of the lead antipsychotic agent tiospirone (1) were synthesized to assist in the identification of the authentic metabolic products found in human urine samples. Thus far, six authentic metabolites have been correlated to the synthetic species. 4a The putative metabolites were further examined in vitro to assess their central nervous system therapeutic potential. SAR analysis of these derivatives indicates that hydroxyl substitution, particularly in the azaspirodecanedione region of the molecule, diminishes the dopamine D-2 affinity of the species without significantly altering the serotonin type-1A and type-2 interactions. In addition, an increase in alpha-1-adrenergic affinity appears to be linked to the attenuation of effects at the dopamine receptors. The biological profile of the 6-hydroxytiospirone metabolite 42 was exemplary in these respects and the in vivo actions of this compound suggest potent antipsychotic potential with a minimal liability for extrapyramidal side effects (EPS). While compound 42 has been unambiguously characterized as an actual human metabolite of tiospirone, the role of 42 in the observed antipsychotic activity of the parent drug, if any, has not yet been determined.