Discovery Of A Novel Class Of Inhaled Dual Pharmacology Muscarinic Antagonist And Beta 2 Agonist (Maba) For The Treatment Of Chronic Obstructive Pulmonary Disease (Copd)
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS(2021)
摘要
The targeting of both the muscarinic and ?-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 ?-adrenergic pharmacologies by the elaboration of the muscarinic inhibitor 7, successfully led to the potent, pharmacologically balanced muscarinic antagonist and ?2 agonist (MABA) 13.
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关键词
Muscarinic antagonist, ?2 agonist, Chronic obstructive pulmonary disease (COPD), Inhaled administration, Dual pharmacology
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