Discovery of (3-endo)-3-(2-cyano-2,2-diphenylethyl)-8,8-dimethyl-8-azoniabicyclo[3.2.1 ]octane bromide as an efficacious inhaled muscarinic acetylcholine receptor antagonist for the treatment of COPD

Abstract Design and syntheses of a novel series of muscarinic antagonists are reported. These efforts have culminated in the discovery of (3- endo )-3-(2-cyano-2,2-diphenylethyl)-8,8-dimethyl-8-azoniabicyclo[3.2.1]octane bromide ( 4a ) as a potent and pan-active muscarinic antagonist as well as a functionally active compound in a murine model of bronchoconstriction. The compound has also displayed pharmacokinetic characteristics suitable for inhaled delivery.