Potent anti-muscarinic activity in a novel series of quinuclidine derivatives.
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.
Starck
Jean-Philippe
JP
UCB Pharma, Chemin du Foriest, 1420 Braine l'Alleud, Belgium.
Talaga
Patrice
P
Quéré
Luc
L
Collart
Philippe
P
Christophe
Bernard
B
Lo Brutto
Patrick
P
Jadot
Sophie
S
Chimmanamada
Dinesh
D
Zanda
Matteo
M
Wagner
Alain
A
Mioskowski
Charles
C
Massingham
Roy
R
Guyaux
Michel
M
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
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