title: Diphenylsulfone muscarinic antagonists: piperidine derivatives with high M2 selectivity and improved potency.
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).
authors.affiliation: Schering-Plough Research Institute, Kenilworth, NJ 07033, USA.
authors.forename: W
authors.initials: W
authors.lastname: Billard
authors.forename: H
authors.initials: H
authors.lastname: Binch
authors.forename: K
authors.initials: K
authors.lastname: Bratzler
authors.forename: L Y
authors.initials: LY
authors.lastname: Chen
authors.forename: G
authors.initials: G
authors.lastname: Crosby
authors.forename: R A
authors.initials: RA
authors.lastname: Duffy
authors.forename: S
authors.initials: S
authors.lastname: Dugar
authors.forename: J
authors.initials: J
authors.lastname: Lachowicz
authors.forename: R
authors.initials: R
authors.lastname: McQuade
authors.forename: P
authors.initials: P
authors.lastname: Pushpavanam
authors.forename: V B
authors.initials: VB
authors.lastname: Ruperto
authors.forename: L A
authors.initials: LA
authors.lastname: Taylor
authors.forename: J W
authors.initials: JW
authors.lastname: Clader
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D015394:Molecular Structure; D018727:Muscarinic Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D018727:Muscarinic Antagonists; D010880:Piperidines; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic; D000109:Acetylcholine