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  • Title: Discovery of a novel class of inhaled dual pharmacology muscarinic antagonist and β2 agonist (MABA) for the treatment of chronic obstructive pulmonary disease (COPD).
    Author: 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.
    Journal: Bioorg Med Chem Lett; 2021 Jun 01; 41():127975. PubMed ID: 33753262.
    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.
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