title: Potent anti-muscarinic activity in a novel series of quinuclidine derivatives.
abstract: The synthesis and biological evaluation of a novel family of M(3) muscarinic antagonists are described. A systematic modification of the substituents to a novel alkyne-quinuclidine scaffold yielded original compounds displaying potent in vitro anticholinergic properties.
authors.affiliation: UCB Pharma, Chemin du Foriest, 1420 Braine l'Alleud, Belgium.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Starck
authors.forename: Patrice
authors.initials: P
authors.lastname: Talaga
authors.forename: Luc
authors.initials: L
authors.lastname: Quéré
authors.forename: Philippe
authors.initials: P
authors.lastname: Collart
authors.forename: Bernard
authors.initials: B
authors.lastname: Christophe
authors.forename: Patrick
authors.initials: P
authors.lastname: Lo Brutto
authors.forename: Sophie
authors.initials: S
authors.lastname: Jadot
authors.forename: Dinesh
authors.initials: D
authors.lastname: Chimmanamada
authors.forename: Matteo
authors.initials: M
authors.lastname: Zanda
authors.forename: Alain
authors.initials: A
authors.lastname: Wagner
authors.forename: Charles
authors.initials: C
authors.lastname: Mioskowski
authors.forename: Roy
authors.initials: R
authors.lastname: Massingham
authors.forename: Michel
authors.initials: M
authors.lastname: Guyaux
mesh_terms: D000818:Animals; D001665:Binding Sites; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D004353:Drug Evaluation, Preclinical; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D015394:Molecular Structure; D018727:Muscarinic Antagonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011812:Quinuclidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D065690:Cytochrome P-450 CYP2D6 Inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D018727:Muscarinic Antagonists; D011812:Quinuclidines; D011976:Receptors, Muscarinic; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A