3-ethyl-8-methyl-1-oxa-3,8-diazaspiro<4.5>decane-2,4-dione

• 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
• 英文名称: 3-ethyl-8-methyl-1-oxa-3,8-diazaspiro<4.5>decane-2,4-dione
• 英文别名: 3-Ethyl-8-methyl-1-oxa-3,8-diaza-spiro[4.5]decane-2,4-dione; hydrochloride；3-ethyl-8-methyl-1-oxa-3,8-diazaspiro[4.5]decane-2,4-dione
• 化学式: C₁₀H₁₆N₂O₃
• 分子量: 212.249
• InChiKey: JVCUVZJRDGGVJT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  49.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-甲基-4-羟基-哌啶-4-二羧酸甲酯 、 异氰酸乙酯 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以92%的产率得到3-ethyl-8-methyl-1-oxa-3,8-diazaspiro<4.5>decane-2,4-dione
  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

• JPS63208590A
  申请人：——

  公开号：JPS63208590A

  公开（公告）日：1988-08-30
• [EN] AZA SPIRO COMPOUNDS ACTING ON THE CHOLINERGIC SYSTEM WITH MUSCARINIC AGONIST ACTIVITY<br/>[FR] AZA SPIRO-COMPOSES AGISSANT SUR LE SYSTEME CHOLINERGIQUE AVEC UNE ACTIVITE AGONISTE MUSCARINIQUE
  申请人：——

  公开号：WO1995003303A2

  公开（公告）日：1995-02-02

  [EN] The invention relates to spiro compounds having central and peripheral nervous system activity, for example muscarinic agonist activity, having formulae (I, II, III, IV, V, VI, VII, VIII and IX) and their pharmaceutically acceptable salts, quaternary compounds which are structurally derived from said compounds having a tertiary nitrogen atom, enantiomers and racemates, wherein ring A together with the spiro-carbon atom constitutes a bridged or unbridged ring containing one or two ring nitrogen atoms, and the value of each of the other symbols in the formulae is defined.
  [FR] Composés présentant une activité au niveau du système nerveux central ou périphérique, par exemple une activité agoniste muscarinique, et répondant aux formules (I, II, III, IV, V, VI, VII, VIII and IX), et leurs sels pharmaceutiquement acceptables, composés quaternaires dérivés structurellement desdits composés et dotés d'un atome d'azote tertiaire, énantiomères et racémates. Dans lesdites formules, le cycle A constitue, conjointement avec l'atome spiro-carbone, un cycle ponté ou non renfermant un ou deux atomes d'azote de cycle, et la valeur de chacun des autres symboles figurant dans les formules est définie.
• 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.