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.
Diouf
O
O
Laboratoire de Chimie Pharmaceutique Organique, Université Libre de Bruxelles, Institut de Pharmacie, Campus Plaine CP205/5, Boulevard du Triomphe, B-1050, Bruxelles, Belgium.
Gadeau
S
S
Chellé
F
F
Gelbcke
M
M
Talaga
P
P
Christophe
B
B
Gillard
M
M
Massingham
R
R
Guyaux
M
M
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