title: Design and synthesis of piperidinyl piperidine analogues as potent and selective M2 muscarinic receptor antagonists.
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.
authors.affiliation: Schering-Plough Research Institute, Kenilworth, NJ 07033, USA. yuguang.wang@spcorp.com
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: S
authors.initials: S
authors.lastname: Chackalamannil
authors.forename: Z
authors.initials: Z
authors.lastname: Hu
authors.forename: J W
authors.initials: JW
authors.lastname: Clader
authors.forename: W
authors.initials: W
authors.lastname: Greenlee
authors.forename: W
authors.initials: W
authors.lastname: Billard
authors.forename: H
authors.initials: H
authors.lastname: Binch
authors.forename: G
authors.initials: G
authors.lastname: Crosby
authors.forename: V
authors.initials: V
authors.lastname: Ruperto
authors.forename: R A
authors.initials: RA
authors.lastname: Duffy
authors.forename: R
authors.initials: R
authors.lastname: McQuade
authors.forename: J E
authors.initials: JE
authors.lastname: Lachowicz
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D015195:Drug Design; D017551:Microdialysis; D018727:Muscarinic Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D043643:Receptor, Muscarinic M1; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D013329:Structure-Activity Relationship
chemical_list: D018727:Muscarinic Antagonists; D010880:Piperidines; D043643:Receptor, Muscarinic M1; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic; D000109:Acetylcholine