3-(3-butyl-1,2,4-oxadiazol-5-yl)quinuclidine | 123685-86-9

• 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-(3-butyl-1,2,4-oxadiazol-5-yl)quinuclidine
• 英文别名: 5-(1-Azabicyclo[2.2.2]octan-3-yl)-3-butyl-1,2,4-oxadiazole
• CAS: 123685-86-9
• 化学式: C₁₃H₂₁N₃O
• 分子量: 235.329
• InChiKey: ISNGKKMSOUVHQA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  42.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-氮杂双环[2.2.2]辛烷-3-羧酸甲酯 、 N'-羟基戊脒 生成 3-(3-butyl-1,2,4-oxadiazol-5-yl)quinuclidine
  参考文献：
  名称：

  SAUERBERG, PER;KINDTLER, JENS W.;NIELSEN, LONE;SHEARDOWN, MALCOLM J.;HONO+, J. MED. CHEM., 34,(1991) N, C. 687-692

  摘要：

  DOI：

文献信息

• Azacyclic compounds and their preparation and use
  申请人：NOVO NORDISK A/S

  公开号：EP0316718A2

  公开（公告）日：1989-05-24

  Novel azacyclic compounds selected from the group consisting of wherein R¹ is H or C₁₋₆-alkyl wherein R′ is C₃₋₈-alkyl, cyclopropyl, C₄₋₈-cycloalkyl, benzyl which may be substituted, or C₁₋₄-alkoxy-C₁₋₄-alkyl, and R˝ is H or C₁₋₈-alkyl or C₁₋₆-alkoxy or C₁₋₄-alkoxy-C₁₋₄-­alkyl or aryl, and R‴ is H or C₁₋₆-alkyl or C₄₋₈-cycloalkyl; and R⁴ is H, C₁₋₈-alkyl or Cl; and provided that R³ is not wherein R′ is C₃₋₈-alkyl, cyclopropyl or C₁₋₃-alkoxymethyl, and provided that R³ is not -CH=N-OR‴, wherein R‴ is H or C₁₋₆-alkyl, when the compounds of formula I is and a salt thereof with a pharmaceutically-acceptable acid. The new compounds are useful in improving the cognitive functions of the forebrain and hippocampus of mammals, and are useful in the treatment of Alzheimer's disease.

  选自以下组别的新型氮杂环化合物 其中 R¹ 是 H 或 C₁₋₆ 烷基 其中 R′是 C₃₋₈-烷基、环丙基、C₄₋₈-环烷基、可能被取代的苄基或 C₁₋₄-alkoxy-C₁₋₄- 烷基，以及 R˝ 是 H 或 C₁₋₈- 烷基或 C₁₋₆- 烷氧基或 C₁₋₄- 烷氧基-C₁₋₄-烷基或芳基，以及 R‴ 是 H 或 C₁₋₆-烷基或 C₄₋₈-环烷基；和 R⁴ 是 H、C₁₋₈-烷基或 Cl；以及 只要 R³ 不是 其中 R′是 C₃₋₈-烷基、环丙基或 C₁₋₃-烷氧基甲基，并且只要 R³ 不是 -CH=N-OR‴，其中 R‴ 是 H 或 C₁₋₆- 烷基，则式 I 的化合物是 及其与药学上可接受的酸的盐。 新化合物有助于改善哺乳动物前脑和海马的认知功能，并可用于治疗阿尔茨海默氏症。
• Muscarinic cholinergic agonists and antagonists of the 3-(3-alkyl-1,2,4-oxadiazol-5-yl)-1,2,5,6-tetrahydropyridine type. Synthesis and structure-activity relationships
  作者：Per Sauerberg、Jens W. Kindtler、Lone Nielsen、Malcolm J. Sheardown、Tage Honore

  DOI：10.1021/jm00106a033

  日期：1991.2

  A series of 3-(3-alkyl-1,2,4-oxadiazol-5-yl)-1,2,5,6-tetrahydro-1-methylpyridines (2a-q) were synthesized and tested for central muscarinic cholinergic receptor binding affinity by using [H-3]oxotremorine-M and [H-3]QNB as ligands and in a functional assay using guinea pig ileum. The analogues with unbranched C1-8-alkyl substituents (2a-g) were agonist, whereas the compounds with branched or cyclic substituents (2h-m) were antagonists. The alkyl ether analogues (2o-q) were also agonists but had lower receptor binding affinity than the corresponding alkyl analogues. The 3-(5-alkyl-1,2,4-oxadiazol-3-yl)-1,2,5,6-tetrahydro-1-methylpyridine analogues had only very low affinity for the central muscarinic receptors and were weak antagonists in the ileum assay. A few 3-(3-butyl-1,2,4-oxadiazol-5-yl)-1,2,5,6-tetrahydro-1-methylpyridines substituted with methyl or hydrogen in the 1-, 5-, or 6-position were synthesized and tested. N-Desmethyl analogue 7 was a potent muscarinic agonist, whereas N-desmethyl-5-methyl analogue 11 and N-methyl-6-methyl analogue 13 both were antagonists with lower muscarinic receptor affinity. The 3-(3-butyl-1,2,4-oxadiazol-5-yl)quinuclidine (17) and tropane (15) analogues were both very potent antagonists with high affinity for central muscarinic receptors. The ratio [IC50(QNB)/IC50(Oxo-M)] x 0.162 proved to be a good indicator of the efficacy of the compounds in the guinea pig ileum assay.
• SAUERBERG, PER;KINDTLER, JENS W.;NIELSEN, LONE;SHEARDOWN, MALCOLM J.;HONO+, J. MED. CHEM., 34,(1991) N, C. 687-692
  作者：SAUERBERG, PER、KINDTLER, JENS W.、NIELSEN, LONE、SHEARDOWN, MALCOLM J.、HONO+

  DOI：——

  日期：——