Synthesis and muscarinic activities of quinuclidin-3-yltriazole and -tetrazole derivatives

J Med Chem. 1992 Apr 3;35(7):1280-90. 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.

MeSH terms

  • Animals
  • Binding, Competitive
  • Cerebral Cortex / metabolism
  • Electrochemistry
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Oxotremorine / metabolism
  • Parasympathomimetics / chemical synthesis*
  • Parasympathomimetics / chemistry
  • Parasympathomimetics / metabolism
  • Quinuclidinyl Benzilate / metabolism
  • Rats
  • Receptors, Muscarinic / metabolism*
  • Structure-Activity Relationship
  • Tetrazoles / chemical synthesis*
  • Tetrazoles / chemistry
  • Tetrazoles / metabolism
  • Triazoles / chemical synthesis*
  • Triazoles / chemistry
  • Triazoles / metabolism


  • Parasympathomimetics
  • Receptors, Muscarinic
  • Tetrazoles
  • Triazoles
  • Oxotremorine
  • Quinuclidinyl Benzilate