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

• Published in: Bioorganic & medicinal chemistry letters Vol. 41; p. 127975
• Main Authors: Rancati, Fabio, Linney, Ian D., Rizzi, Andrea, Delcanale, Maurizio, Knight, Chris K., Schmidt, Wolfgang, Pastore, Fiorella, Riccardi, Benedetta, Mileo, Valentina, Carnini, Chiara, Cesari, Nicola, Blackaby, Wesley P., Patacchini, Riccardo, Carzaniga, Laura
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.06.2021
• Subjects: Chronic obstructive pulmonary disease (COPD); Dual pharmacology; Inhaled administration; Muscarinic antagonist; β2 agonist; Chronic obstructive pulmonary disease (COPD); Muscarinic antagonist; Dual pharmacology; β2 agonist; Inhaled administration
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2021.127975

[Display omitted] 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.