A new series of M3 muscarinic antagonists based on the 4-amino-piperidine scaffold

A series of 4-amino-piperidine containing molecules have been synthesized and structure–affinity relationship toward the M3-muscarinic receptor has been investigated. Chemical modulations provided molecules with Ki for the human M3-R up to 1 nM with variable selectivity (3- to 40-fold) over the human M2-R. Compounds 2 (pA2=8.3, 8.6) demonstrates in vitro on guinea pig bladder and ileal strips potent anticholinergic properties and tissue selectivity.