Design and synthesis of piperidinyl piperidine analogues as potent and selective M2 muscarinic receptor antagonists

Y Wang; S Chackalamannil; Z Hu; J W Clader; W Greenlee; W Billard; H Binch; G Crosby; V Ruperto; R A Duffy; R McQuade; J E Lachowicz

doi:10.1016/s0960-894x(00)00457-1

Design and synthesis of piperidinyl piperidine analogues as potent and selective M2 muscarinic receptor antagonists

Bioorg Med Chem Lett. 2000 Oct 16;10(20):2247-50. doi: 10.1016/s0960-894x(00)00457-1.

Authors

Y Wang¹, S Chackalamannil, Z Hu, J W Clader, W Greenlee, W Billard, H Binch, G Crosby, V Ruperto, R A Duffy, R McQuade, J E Lachowicz

Affiliation

¹ Schering-Plough Research Institute, Kenilworth, NJ 07033, USA. [email protected]

PMID: 11055330
DOI: 10.1016/s0960-894x(00)00457-1

Abstract

Identification of a number of highly potent M2 receptor antagonists with >100-fold selectivity against the M1 and M3 receptor subtypes is described. In the rat microdialysis assay, this series of compounds showed pronounced enhancement of brain acetylcholine release after oral administration.

MeSH terms

Acetylcholine / metabolism
Administration, Oral
Animals
Brain / drug effects
Brain / metabolism
Drug Design
Microdialysis
Muscarinic Antagonists / chemical synthesis*
Muscarinic Antagonists / chemistry
Muscarinic Antagonists / pharmacology
Piperidines / chemical synthesis*
Piperidines / chemistry
Piperidines / pharmacology
Rats
Receptor, Muscarinic M1
Receptor, Muscarinic M2
Receptors, Muscarinic / drug effects
Receptors, Muscarinic / physiology*
Structure-Activity Relationship

Substances

Muscarinic Antagonists
Piperidines
Receptor, Muscarinic M1
Receptor, Muscarinic M2
Receptors, Muscarinic
Acetylcholine