Synthesis of azabicyclic pyrazine derivatives as muscarinic agonists and the preparation of a chloropyrazine analogue with functional selectivity at sub-types of the muscarinic receptor

Abstract

The synthesis of quinuclidine and azanorbornyl pyrazine derivatives has yielded highly potent and efficacious muscarinic agonists; chloro-substitution in the pyrazine ring of the quinuclidine analogue resulted in the formation of a derivative with both enantiomers displaying partial agonist character but, more importantly, functional selectivity at the M₁, M₂ and M₃ sub-types of the muscarinic receptor.