8-<4-<4-(1,2-benzisothiazol-3-yl)-1-piperazinyl>butyl>-6-<<<(4-nitrobenzyl)oxy>carbonyl>oxy>-8-azaspiro<4.5>decane-7,9-dione S,S-dioxide | 136546-59-3

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: 8-<4-<4-(1,2-benzisothiazol-3-yl)-1-piperazinyl>butyl>-6-<<<(4-nitrobenzyl)oxy>carbonyl>oxy>-8-azaspiro<4.5>decane-7,9-dione S,S-dioxide
• 英文别名: 8-{4-[4-(1,2-benzisothiazol-3-yl)-1-piperazinyl]butyl}-6-({[(4-nitrobenzyl)oxy]carbonyl}oxy)-8-azaspiro[4.5]decane-7,9-dione S,S-dioxide；[8-[4-[4-(1,1-dioxo-1,2-benzothiazol-3-yl)piperazin-1-yl]butyl]-7,9-dioxo-8-azaspiro[4.5]decan-10-yl] (4-nitrophenyl)methyl carbonate
• CAS: 136546-59-3
• 化学式: C₃₂H₃₇N₅O₉S
• 分子量: 667.74
• InChiKey: FMSSCLZQFPMTED-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.48
• 重原子数：
  47.0
• 可旋转键数：
  9.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  169.03
• 氢给体数：
  0.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  8-<4-<4-(1,2-benzisothiazol-3-yl)-1-piperazinyl>butyl>-6-<<<(4-nitrobenzyl)oxy>carbonyl>oxy>-8-azaspiro<4.5>decane-7,9-dione S,S-dioxide 在 palladium on activated charcoal 氢气 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 2.5h， 以66%的产率得到8-<4-<4-(1,2-benzisothiazol-3-yl)-1-piperazinyl>butyl>-6-hydroxy-8-azaspiro<4.5>decane-7,9-dione S,S-dioxide
  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
• 作为产物：
  描述：

  8-{4-[4-(1,2-苯并噻唑-3-基)-1-哌嗪基]丁基}-8-氮杂螺[4.5]癸烷-7,9-二酮 在 Oxone 、 lithium hexamethyldisilazane 作用下， 以 甲醇 为溶剂， 反应 6.5h， 生成 8-<4-<4-(1,2-benzisothiazol-3-yl)-1-piperazinyl>butyl>-6-<<<(4-nitrobenzyl)oxy>carbonyl>oxy>-8-azaspiro<4.5>decane-7,9-dione S,S-dioxide
  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