title: Improving the oral efficacy of CNS drug candidates: discovery of highly orally efficacious piperidinyl piperidine M2 muscarinic receptor antagonists.
abstract: In search of a backup M(2) muscarinic receptor antagonist to the previously reported compound 1, we discovered compound (+)-14, which showed superior oral efficacy in animal models. The improvement of oral efficacy was achieved by modulating both the molecular weight and lipophilicity of the lead compounds.
authors.affiliation: Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, USA. yuguang.wang@spcorp.com
authors.forename: Yuguang
authors.initials: Y
authors.lastname: Wang
authors.forename: Samuel
authors.initials: S
authors.lastname: Chackalamannil
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Hu
authors.forename: William J
authors.initials: WJ
authors.lastname: Greenlee
authors.forename: John
authors.initials: J
authors.lastname: Clader
authors.forename: Craig D
authors.initials: CD
authors.lastname: Boyle
authors.forename: James J
authors.initials: JJ
authors.lastname: Kaminski
authors.forename: William
authors.initials: W
authors.lastname: Billard
authors.forename: Herbert
authors.initials: H
authors.lastname: Binch
authors.forename: Gordon
authors.initials: G
authors.lastname: Crosby
authors.forename: Vilma
authors.initials: V
authors.lastname: Ruperto
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Duffy
authors.forename: Mary
authors.initials: M
authors.lastname: Cohen-Williams
authors.forename: Vicki L
authors.initials: VL
authors.lastname: Coffin
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Cox
authors.forename: Diane E
authors.initials: DE
authors.lastname: Grotz
authors.forename: Jean E
authors.initials: JE
authors.lastname: Lachowicz
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D017660:Autoreceptors / Q000037:antagonists & inhibitors*; D001362:Avoidance Learning / Q000187:drug effects; D002491:Central Nervous System Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D017551:Microdialysis; D008968:Molecular Conformation; 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 / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D017660:Autoreceptors; D002491:Central Nervous System Agents; D018727:Muscarinic Antagonists; D010880:Piperidines; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic; D000109:Acetylcholine