These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: 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.
    Author: Sauerberg P, Kindtler JW, Nielsen L, Sheardown MJ, Honoré T.
    Journal: J Med Chem; 1991 Feb; 34(2):687-92. PubMed ID: 1995893.
    Abstract:
    A series of 3-(3-alkyl-1,2,4-oxadiazol-5-yl)-1,2,5,6-tetrahydro-1-methylpyr idines (2a-q) were synthesized and tested for central muscarinic cholinergic receptor binding affinity by using [3H]oxotremorine-M and [3H]QNB as ligands and in a functional assay using guinea pig ileum. The analogues with unbranched C1-8-alkyl substituents (2a-g) were agonists, 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-methylpyridi ne analogues had only ver 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-methylpyr idines 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.
    [Abstract] [Full Text] [Related] [New Search]