Synthesis and Muscarinic Activities of Quinuclidin-3-yltriazole and -tetrazole Derivatives

Article abstract of DOI:10.1021/jm00085a016

The synthesis of 15 methyl or unsubstituted 1,2,3-triazoles, 1,2,4-triazoles, and tetrazoles additionally substituted with a 1-azabicyclo<2.2.2>octan-3-yl group is described.The potency and efficacy of these compounds as muscarinic ligands were determined in radioligand binding assays using <3H>oxotremorine and <3H>quinuclidinyl benzilate.Potency and efficacy were found in compounds in which the azole moiety was attached to the azabicyclic ring either through a carbon atom or a nitrogen atom.Electrostatic potential maps of both the C-linked and the novel N-linked series of compounds were calculated.A relationship between position and depth of the electrostatic minima relative to the azabicyclic ring and the potency and efficacy of the compounds was determined.