title: Discovery of novel quaternary ammonium derivatives of (3R)-quinuclidinyl amides as potent and long acting muscarinic antagonists.
abstract: Novel quaternary ammonium derivatives of (3R)-quinuclidinyl amides have been identified as potent M3 muscarinic antagonists with a long duration of action in an in vivo model of bronchoconstriction. The synthesis, structure-activity relationships and biological evaluation of this series of compounds are reported.
authors: Almirall, R&D Centre, Laureà Miró 408-410, Sant Feliu de Llobregat, 08980 Barcelona, Spain. Electronic address: maria.prat@almirall.com.
authors: Maria
authors: M
authors: Prat
authors: Almirall, R&D Centre, Laureà Miró 408-410, Sant Feliu de Llobregat, 08980 Barcelona, Spain.
authors: María Antonia
authors: MA
authors: Buil
authors: Thomson Reuters, Provenza 398, 08025 Barcelona, Spain.
authors: Maria Dolors
authors: MD
authors: Fernández
authors: Almirall, R&D Centre, Laureà Miró 408-410, Sant Feliu de Llobregat, 08980 Barcelona, Spain.
authors: Laia
authors: L
authors: Tort
authors: Almirall, R&D Centre, Laureà Miró 408-410, Sant Feliu de Llobregat, 08980 Barcelona, Spain.
authors: Juan Manuel
authors: JM
authors: Monleón
authors: Almirall, R&D Centre, Laureà Miró 408-410, Sant Feliu de Llobregat, 08980 Barcelona, Spain.
authors: Gaspar
authors: G
authors: Casals
authors: Almirall, R&D Centre, Laureà Miró 408-410, Sant Feliu de Llobregat, 08980 Barcelona, Spain.
authors: Manuel
authors: M
authors: Ferrer
authors: Almirall, R&D Centre, Laureà Miró 408-410, Sant Feliu de Llobregat, 08980 Barcelona, Spain.
authors: Jordi
authors: J
authors: Castro
authors: Almirall, R&D Centre, Laureà Miró 408-410, Sant Feliu de Llobregat, 08980 Barcelona, Spain.
authors: Amadeu
authors: A
authors: Gavaldà
authors: Almirall, R&D Centre, Laureà Miró 408-410, Sant Feliu de Llobregat, 08980 Barcelona, Spain.
authors: Montserrat
authors: M
authors: Miralpeix
authors: Almirall, R&D Centre, Laureà Miró 408-410, Sant Feliu de Llobregat, 08980 Barcelona, Spain.
authors: Israel
authors: I
authors: Ramos
authors: Almirall, R&D Centre, Laureà Miró 408-410, Sant Feliu de Llobregat, 08980 Barcelona, Spain.
authors: Dolors
authors: D
authors: Vilella
authors: Almirall, R&D Centre, Laureà Miró 408-410, Sant Feliu de Llobregat, 08980 Barcelona, Spain.
authors: Josep Maria
authors: JM
authors: Huerta
authors: Almirall, R&D Centre, Laureà Miró 408-410, Sant Feliu de Llobregat, 08980 Barcelona, Spain.
authors: Sònia
authors: S
authors: Espinosa
authors: Almirall, R&D Centre, Laureà Miró 408-410, Sant Feliu de Llobregat, 08980 Barcelona, Spain.
authors: Begoña
authors: B
authors: Hernández
authors: Almirall, R&D Centre, Laureà Miró 408-410, Sant Feliu de Llobregat, 08980 Barcelona, Spain.
authors: Victor
authors: V
authors: Segarra
authors: Almirall, R&D Centre, Laureà Miró 408-410, Sant Feliu de Llobregat, 08980 Barcelona, Spain.
authors: Mònica
authors: M
authors: Córdoba
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D000818:Animals; D001665:Binding Sites; D016085:Bronchoconstrictor Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D004353:Drug Evaluation, Preclinical; D006207:Half-Life; D006801:Humans; D006860:Hydrogen Bonding; D062105:Molecular Docking Simulation; D018727:Muscarinic Antagonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D000644:Quaternary Ammonium Compounds / Q000737:chemistry*; D011812:Quinuclidines / Q000737:chemistry*; D051381:Rats; D043587:Receptor, Muscarinic M3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D016085:Bronchoconstrictor Agents; D018727:Muscarinic Antagonists; D000644:Quaternary Ammonium Compounds; D011812:Quinuclidines; D043587:Receptor, Muscarinic M3
keywords: (3R)-Quinuclidinyl amides; COPD; Long acting bronchodilators; Low systemic exposure; M(3) muscarinic antagonists