3-(4-Ethoxy-[1,2,5]thiadiazol-3-yloxy)-1-aza-bicyclo[2.2.2]octane

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 奎宁环
• 英文名称: 3-(4-Ethoxy-[1,2,5]thiadiazol-3-yloxy)-1-aza-bicyclo[2.2.2]octane
• 英文别名: 3-(1-azabicyclo[2.2.2]octan-3-yloxy)-4-ethoxy-1,2,5-thiadiazole
• 化学式: C₁₁H₁₇N₃O₂S
• 分子量: 255.341
• InChiKey: ZDIGSPWEOMQNHN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  75.7
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3-chloro-4-ethoxy-[1,2,5]thiadiazole 、 奎宁环-3-醇 在 potassium tert-butylate 作用下， 生成 3-(4-Ethoxy-[1,2,5]thiadiazol-3-yloxy)-1-aza-bicyclo[2.2.2]octane
  参考文献：
  名称：

  1,2,5-Thiadiazole Analogues of Aceclidine as Potent m₁ Muscarinic Agonists

  摘要：

  The acetyl group of the muscarinic agonist aceclidine 4 was replaced by various 1,2,5-thiadiazoles to provide a new series of potent m(1) muscarinic agonists 17 and 18. Optimal mi muscarinic agonist potency was achieved when the 1,2,g-thiadiazole substituent was either a butyloxy, 17d, or butylthio, 18d, group. Although 1,2,5-oxadiazole 37 and pyrazine 39 are iso-pi-electronic with 1,2,5-thiadiazole 17d, both analogues were substantially less active than 17d. Compounds with high muscarinic affinity and/or m(1) muscarinic agonist efficacy were also obtained when the 3-oxyquinuclidine moiety of 17d or 18c was replaced by ethanolamines, hydroxypyrrolidines, hydroxyazetidine, hydroxyisotropanes, or hydroxyazanorbornanes. The structure-activity data support the participation of the oxygen or sulfur atom in the substituent on the 1,2,5-thiadiazole in the activation of the m(1) receptor. Several of these new 1,2,5-thiadiazoles have m(1) agonist efficacy, potency, and selectivity comparable to those of xanomeline 2 in the muscarinic tests investigated.

  DOI：

  10.1021/jm970125n

文献信息

• 1,2,5-Thiadiazole Analogues of Aceclidine as Potent m₁ Muscarinic Agonists
  作者：John S. Ward、Leander Merritt、David O. Calligaro、Franklin P. Bymaster、Harlan E. Shannon、Charles H. Mitch、Celia Whitesitt、David Brunsting、Malcolm J. Sheardown、Preben H. Olesen、Michael D. B. Swedberg、Lone Jeppesen、Per Sauerberg

  DOI：10.1021/jm970125n

  日期：1998.1.1

  The acetyl group of the muscarinic agonist aceclidine 4 was replaced by various 1,2,5-thiadiazoles to provide a new series of potent m(1) muscarinic agonists 17 and 18. Optimal mi muscarinic agonist potency was achieved when the 1,2,g-thiadiazole substituent was either a butyloxy, 17d, or butylthio, 18d, group. Although 1,2,5-oxadiazole 37 and pyrazine 39 are iso-pi-electronic with 1,2,5-thiadiazole 17d, both analogues were substantially less active than 17d. Compounds with high muscarinic affinity and/or m(1) muscarinic agonist efficacy were also obtained when the 3-oxyquinuclidine moiety of 17d or 18c was replaced by ethanolamines, hydroxypyrrolidines, hydroxyazetidine, hydroxyisotropanes, or hydroxyazanorbornanes. The structure-activity data support the participation of the oxygen or sulfur atom in the substituent on the 1,2,5-thiadiazole in the activation of the m(1) receptor. Several of these new 1,2,5-thiadiazoles have m(1) agonist efficacy, potency, and selectivity comparable to those of xanomeline 2 in the muscarinic tests investigated.