A new series of M3 muscarinic antagonists based on the 4-amino-piperidine scaffold

• Published in: Bioorganic & medicinal chemistry letters 2002-09, Vol.12 (18), p.2535-2539
• Main Authors: Diouf, O, Gadeau, S, Chellé, F, Gelbcke, M, Talaga, P, Christophe, B, Gillard, M, Massingham, R, Guyaux, M
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cholinergic system; Guinea Pigs; Ileum - drug effects; Ileum - physiology; In Vitro Techniques; Medical sciences; Muscarinic Antagonists - pharmacology; Muscle Contraction - drug effects; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Pharmacology. Drug treatments; Piperidines - pharmacology; Receptor, Muscarinic M3; Receptors, Muscarinic - drug effects; Urinary Bladder - drug effects; Urinary Bladder - physiology
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(02)00487-0

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 (p A 2=8.3, 8.6) demonstrates in vitro on guinea pig bladder and ileal strips potent anticholinergic properties and tissue selectivity. 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 (p A 2=8.3, 8.6) demonstrates in vitro on guinea pig bladder and ileal strips potent anticholinergic properties and tissue selectivity.