title: Discovery of novel quaternary ammonium derivatives of (3R)-quinuclidinyl carbamates as potent and long acting muscarinic antagonists.
abstract: Novel quaternary ammonium derivatives of N,N-disubstituted (3R)-quinuclidinyl carbamates have been identified as potent M(3) muscarinic antagonists with long duration of action in an in vivo model of bronchoconstriction. These compounds have also presented a high level of metabolic transformation (human liver microsomes). The synthesis, structure-activity relationships and biological evaluation of these compounds are reported.
authors.affiliation: Almirall, R&D Centre, Laureà Miró 408-410, Sant Feliu de Llobregat, 08980 Barcelona, Spain. maria.prat@almirall.com
authors.forename: Maria
authors.initials: M
authors.lastname: Prat
authors.forename: María Antonia
authors.initials: MA
authors.lastname: Buil
authors.forename: Maria Dolors
authors.initials: MD
authors.lastname: Fernández
authors.forename: Jordi
authors.initials: J
authors.lastname: Castro
authors.forename: Juan Manuel
authors.initials: JM
authors.lastname: Monleón
authors.forename: Laia
authors.initials: L
authors.lastname: Tort
authors.forename: Gaspar
authors.initials: G
authors.lastname: Casals
authors.forename: Manuel
authors.initials: M
authors.lastname: Ferrer
authors.forename: Josep Maria
authors.initials: JM
authors.lastname: Huerta
authors.forename: Sònia
authors.initials: S
authors.lastname: Espinosa
authors.forename: Manuel
authors.initials: M
authors.lastname: López
authors.forename: Victor
authors.initials: V
authors.lastname: Segarra
authors.forename: Amadeu
authors.initials: A
authors.lastname: Gavaldà
authors.forename: Montserrat
authors.initials: M
authors.lastname: Miralpeix
authors.forename: Israel
authors.initials: I
authors.lastname: Ramos
authors.forename: Dolors
authors.initials: D
authors.lastname: Vilella
authors.forename: Marisa
authors.initials: M
authors.lastname: González
authors.forename: Mònica
authors.initials: M
authors.lastname: Córdoba
authors.forename: Alvaro
authors.initials: A
authors.lastname: Cárdenas
authors.forename: Francisca
authors.initials: F
authors.lastname: Antón
authors.forename: Jorge
authors.initials: J
authors.lastname: Beleta
authors.forename: Hamish
authors.initials: H
authors.lastname: Ryder
mesh_terms: D002219:Carbamates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D055808:Drug Discovery; D006801:Humans; D020128:Inhibitory Concentration 50; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D015394:Molecular Structure; D018727:Muscarinic Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000644:Quaternary Ammonium Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011812:Quinuclidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013997:Time Factors
chemical_list: D002219:Carbamates; D018727:Muscarinic Antagonists; D000644:Quaternary Ammonium Compounds; D011812:Quinuclidines