Discovery of a novel class of inhaled dual pharmacology muscarinic antagonist and β2 agonist (MABA) for the treatment of chronic obstructive pulmonary disease (COPD)

Abstract

The targeting of both the muscarinic and β-adrenergic pathways is a well validated therapeutic approach for the treatment of chronic obstructive pulmonary disease (COPD). In this communication we report our effort to incorporate two pharmacologies into a single chemical entity, whose characteristic must be suitable for a once daily inhaled administration. Contextually, we aimed at a locally acting therapy with limited systemic absorption to minimize side effects. Our lung-tailored design of bifunctional compounds that combine the muscarinic and β-adrenergic pharmacologies by the elaboration of the muscarinic inhibitor 7, successfully led to the potent, pharmacologically balanced muscarinic antagonist and β₂ agonist (MABA) 13.

Keywords: Chronic obstructive pulmonary disease (COPD); Dual pharmacology; Inhaled administration; Muscarinic antagonist; β(2) agonist.