Discovery of a novel class of inhaled dual pharmacology muscarinic antagonist and β2 agonist (MABA) for the treatment of chronic obstructive pulmonary disease (COPD). (1st June 2021)

• Record Type: Journal Article
• 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
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 41(2021)
• Publication Date: 2021-06-01
• Subjects: Muscarinic antagonist -- β2 agonist -- Chronic obstructive pulmonary disease (COPD) -- Inhaled administration -- Dual pharmacology; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2021.127975
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: 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 .