8-甲基-1-氧杂-3,8-二氮杂螺[4.5]癸烷-2,4-二酮 | 168818-35-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂螺癸烷衍生物
• 中文名称: 8-甲基-1-氧杂-3,8-二氮杂螺[4.5]癸烷-2,4-二酮
• 英文名称: 8-methyl-1-oxa-3,8-diazaspiro<4.5>decane-2,4-dione
• 英文别名: 8-Methyl-1-oxa-3,8-diazaspiro[4.5]decane-2,4-dione
• CAS: 168818-35-7
• 化学式: C₈H₁₂N₂O₃
• 分子量: 184.195
• InChiKey: IODIRNHGMQEBBK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  8-甲基-1-氧杂-3,8-二氮杂螺[4.5]癸烷-2,4-二酮 在 ammonium hydroxide 、 sodium hydride 作用下， 以 甲醇 为溶剂， 反应 99.25h， 生成 2,4-dioxo-8-methyl-1-oxa-3,8-diazaspiro<4.5>decan-3-ylacetamide
  参考文献：
  名称：

  Synthesis and structure-activity studies of a series of spirooxazolidine-2,4-diones: 4-oxa-analogs of the muscarinic agonist 2-ethyl-8-methyl-2,8-diazaspiro[4.5]decane-1,3-dione

  摘要：

  A series of spirooxazolidine-2,4-dione derivatives related to the putative M, agonist 2-ethyl-8-methyl-2,8-diazaspiro[4.5]decane-1,3-dione (RS86; 1) were synthesized. The compounds were evaluated as cholinergic agents in in vitro binding assays and in in vivo pharmacological tests including antiamnesic effects using scopolamine-treated mice, hypothermia, and salivation in mice. Four compounds (5a,c,f and 17a) exhibited affinity for cortical M1 receptors and reversed scopolamine-induced impairment of mouse passive avoidance tasks, as did 1. Among these compounds, only 5a exhibited M1-receptor stimulating activity in pithed rats. Structural requirements for muscarinic activity in this series of spirooxazolidine-2,4-dione derivatives were as strict as those reported for spirosuccinimide derivatives including 1. The antiamnesic dose of 3-ethyl-8-methyl-1-oxa-3,8-diazaspiro[4.5]decane-2,4-dione (5a) was 2 orders of magnitude lower than the doses inducing hypothermia and salivation, in contrast to 1 for which the former dose was only 5-10-fold lower than the latter. These results suggest that the 8-azaspiro[4.5]decane skeleton represents a useful template for designing new muscarinic agonists as antidementia drugs.

  DOI：

  10.1021/jm00068a005
• 作为产物：
  描述：

  1-甲基-4-羟基-哌啶-4-二羧酸甲酯 、 尿素 在 sodium ethanolate 作用下， 以 乙醇 为溶剂， 反应 10.0h， 生成 8-甲基-1-氧杂-3,8-二氮杂螺[4.5]癸烷-2,4-二酮
  参考文献：
  名称：

  Synthesis and structure-activity studies of a series of spirooxazolidine-2,4-diones: 4-oxa-analogs of the muscarinic agonist 2-ethyl-8-methyl-2,8-diazaspiro[4.5]decane-1,3-dione

  摘要：

  A series of spirooxazolidine-2,4-dione derivatives related to the putative M, agonist 2-ethyl-8-methyl-2,8-diazaspiro[4.5]decane-1,3-dione (RS86; 1) were synthesized. The compounds were evaluated as cholinergic agents in in vitro binding assays and in in vivo pharmacological tests including antiamnesic effects using scopolamine-treated mice, hypothermia, and salivation in mice. Four compounds (5a,c,f and 17a) exhibited affinity for cortical M1 receptors and reversed scopolamine-induced impairment of mouse passive avoidance tasks, as did 1. Among these compounds, only 5a exhibited M1-receptor stimulating activity in pithed rats. Structural requirements for muscarinic activity in this series of spirooxazolidine-2,4-dione derivatives were as strict as those reported for spirosuccinimide derivatives including 1. The antiamnesic dose of 3-ethyl-8-methyl-1-oxa-3,8-diazaspiro[4.5]decane-2,4-dione (5a) was 2 orders of magnitude lower than the doses inducing hypothermia and salivation, in contrast to 1 for which the former dose was only 5-10-fold lower than the latter. These results suggest that the 8-azaspiro[4.5]decane skeleton represents a useful template for designing new muscarinic agonists as antidementia drugs.

  DOI：

  10.1021/jm00068a005

文献信息

• Synthesis and structure-activity studies of a series of spirooxazolidine-2,4-diones: 4-oxa-analogs of the muscarinic agonist 2-ethyl-8-methyl-2,8-diazaspiro[4.5]decane-1,3-dione
  作者：Shinichi Tsukamoto、Masato Ichihara、Fumikazu Wanibuchi、Shinji Usuda、Kazuyuki Hidaka、Masatomi Harada、Toshinari Tamura

  DOI：10.1021/jm00068a005

  日期：1993.8

  A series of spirooxazolidine-2,4-dione derivatives related to the putative M, agonist 2-ethyl-8-methyl-2,8-diazaspiro[4.5]decane-1,3-dione (RS86; 1) were synthesized. The compounds were evaluated as cholinergic agents in in vitro binding assays and in in vivo pharmacological tests including antiamnesic effects using scopolamine-treated mice, hypothermia, and salivation in mice. Four compounds (5a,c,f and 17a) exhibited affinity for cortical M1 receptors and reversed scopolamine-induced impairment of mouse passive avoidance tasks, as did 1. Among these compounds, only 5a exhibited M1-receptor stimulating activity in pithed rats. Structural requirements for muscarinic activity in this series of spirooxazolidine-2,4-dione derivatives were as strict as those reported for spirosuccinimide derivatives including 1. The antiamnesic dose of 3-ethyl-8-methyl-1-oxa-3,8-diazaspiro[4.5]decane-2,4-dione (5a) was 2 orders of magnitude lower than the doses inducing hypothermia and salivation, in contrast to 1 for which the former dose was only 5-10-fold lower than the latter. These results suggest that the 8-azaspiro[4.5]decane skeleton represents a useful template for designing new muscarinic agonists as antidementia drugs.