5-Methoxy-3-piperazin-1-yl-benzo[d]isothiazole; hydrochloride | 136546-56-0

• 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: 5-Methoxy-3-piperazin-1-yl-benzo[d]isothiazole; hydrochloride
• CAS: 136546-56-0
• 化学式: C₁₂H₁₅N₃OS*ClH
• 分子量: 285.798
• InChiKey: XVGZHZKTOBFJDX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.14
• 重原子数：
  18.0
• 可旋转键数：
  2.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  37.39
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为产物：
  描述：

  2-溴-5-甲氧基苯甲酸 在 盐酸 、 sodium hydroxide 、 正丁基锂 、 五氯化磷 、 氯甲酸三氯甲酯 作用下， 以 二氯甲烷 为溶剂， 反应 2.25h， 生成 5-Methoxy-3-piperazin-1-yl-benzo[d]isothiazole; hydrochloride
  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

• 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.