A new series of M3 muscarinic antagonists based on the 4-amino-piperidine scaffold.
A series of 4-amino-piperidine containing molecules have been synthesized and structure-affinity relationship toward the M3-muscarinic receptor has been investigated. Chemical modulations provided molecules with K(i) for the human M3-R up to 1 nM with variable selectivity (3- to 40-fold) over the human M2-R. Compounds 2 (pA(2)=8.3, 8.6) demonstrates in vitro on guinea pig bladder and ileal strips potent anticholinergic properties and tissue selectivity.
Laboratoire de Chimie Pharmaceutique Organique, Université Libre de Bruxelles, Institut de Pharmacie, Campus Plaine CP205/5, Boulevard du Triomphe, B-1050, Bruxelles, Belgium.
O
O
Diouf
S
S
Gadeau
F
F
Chellé
M
M
Gelbcke
P
P
Talaga
B
B
Christophe
M
M
Gillard
R
R
Massingham
M
M
Guyaux
D000818:Animals; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology*; D043587:Receptor, Muscarinic M3; D011976:Receptors, Muscarinic / Q000187:drug effects*; D001743:Urinary Bladder / Q000187:drug effects / Q000502:physiology
D018727:Muscarinic Antagonists; D010880:Piperidines; D043587:Receptor, Muscarinic M3; D011976:Receptors, Muscarinic