Diphenylsulfone muscarinic antagonists: piperidine derivatives with high M2 selectivity and improved potency

W Billard; H Binch; K Bratzler; L Y Chen; G Crosby Jr; R A Duffy; S Dugar; J Lachowicz; R McQuade; P Pushpavanam; V B Ruperto; L A Taylor; J W Clader

doi:10.1016/s0960-894x(00)00437-6

Diphenylsulfone muscarinic antagonists: piperidine derivatives with high M2 selectivity and improved potency

Bioorg Med Chem Lett. 2000 Oct 2;10(19):2209-12. doi: 10.1016/s0960-894x(00)00437-6.

Authors

W Billard¹, H Binch, K Bratzler, L Y Chen, G Crosby Jr, R A Duffy, S Dugar, J Lachowicz, R McQuade, P Pushpavanam, V B Ruperto, L A Taylor, J W Clader

Affiliation

¹ Schering-Plough Research Institute, Kenilworth, NJ 07033, USA.

PMID: 11012031
DOI: 10.1016/s0960-894x(00)00437-6

Abstract

Piperidine analogues of our previously described piperazine muscarinic antagonists are described. Piperidine analogues show a distinct structure-activity relationship (SAR) that differs from comparable piperazines. Compounds with high selectivity and improved potency for the M2 receptor have been identified. The lead compound, 12b, increases acetylcholine release in vivo. Compounds of this class may be useful for the treatment of cognitive disorders such as Alzheimer's disease (AD).

MeSH terms

Acetylcholine / metabolism
Animals
Corpus Striatum / drug effects
Corpus Striatum / metabolism
Molecular Structure
Muscarinic Antagonists / chemical synthesis*
Muscarinic Antagonists / chemistry
Muscarinic Antagonists / pharmacology*
Piperidines / chemical synthesis*
Piperidines / chemistry
Piperidines / pharmacology*
Rats
Receptor, Muscarinic M2
Receptors, Muscarinic / metabolism*
Structure-Activity Relationship

Substances

Muscarinic Antagonists
Piperidines
Receptor, Muscarinic M2
Receptors, Muscarinic
Acetylcholine