1-methyl-3-(3-butyl-1,2,4-oxadiazol-5-yl)-1,2,5,6-tetrahydropyridine | 114904-63-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 1-methyl-3-(3-butyl-1,2,4-oxadiazol-5-yl)-1,2,5,6-tetrahydropyridine
• 英文别名: 3-butyl-5-(1-methyl-3,6-dihydro-2H-pyridin-5-yl)-1,2,4-oxadiazole
• CAS: 114904-63-1
• 化学式: C₁₂H₁₉N₃O
• 分子量: 221.302
• InChiKey: KMIVBEKWYNAAHN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 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：

  N'-羟基戊脒 、 氢溴酸槟榔碱 在 4 A molecular sieve 、 sodium 作用下， 生成 1-methyl-3-(3-butyl-1,2,4-oxadiazol-5-yl)-1,2,5,6-tetrahydropyridine
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1021/jm00106a033

文献信息

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

  公开号：EP0259621B1

  公开（公告）日：1992-11-25
• US4837241A
  申请人：——

  公开号：US4837241A

  公开（公告）日：1989-06-06