Discovery of a novel class of inhaled dual pharmacology muscarinic antagonist and β<sub>2</sub> agonist (MABA) for the treatment of chronic obstructive pulmonary disease (COPD).
Rancati F, Linney ID, Rizzi A, Delcanale M, Knight CK, Schmidt W, Pastore F, Riccardi B, Mileo V, Carnini C, Cesari N, Blackaby WP, Patacchini R, Carzaniga L.
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 β<sub>2</sub> agonist (MABA) 13.