title: M3 muscarinic acetylcholine receptor antagonists: SAR and optimization of bi-aryl amines.
abstract: Exploration of multiple regions of a bi-aryl amine template led to the identification of highly potent M(3) muscarinic acetylcholine receptor antagonists such as 14 (pA(2)=11.0) possessing good sub-type selectivity for M(3) over M(2). The structure-activity relationships (SAR) and optimization of the bi-aryl amine series are described.
authors.affiliation: Centers of Excellence for Drug Discovery, GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, PA 19426, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Budzik
authors.forename: Yonghui
authors.initials: Y
authors.lastname: Wang
authors.forename: Dongchuan
authors.initials: D
authors.lastname: Shi
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.forename: Haibo
authors.initials: H
authors.lastname: Xie
authors.forename: Zehong
authors.initials: Z
authors.lastname: Wan
authors.forename: Chongye
authors.initials: C
authors.lastname: Zhu
authors.forename: James J
authors.initials: JJ
authors.lastname: Foley
authors.forename: Parvathi
authors.initials: P
authors.lastname: Nuthulaganti
authors.forename: Lorena A
authors.initials: LA
authors.lastname: Kallal
authors.forename: Henry M
authors.initials: HM
authors.lastname: Sarau
authors.forename: Dwight M
authors.initials: DM
authors.lastname: Morrow
authors.forename: Michael L
authors.initials: ML
authors.lastname: Moore
authors.forename: Ralph A
authors.initials: RA
authors.lastname: Rivero
authors.forename: Michael
authors.initials: M
authors.lastname: Palovich
authors.forename: Michael
authors.initials: M
authors.lastname: Salmon
authors.forename: Kristen E
authors.initials: KE
authors.lastname: Belmonte
authors.forename: Dramane I
authors.initials: DI
authors.lastname: Laine
authors.forename: Jian
authors.initials: J
authors.lastname: Jin
mesh_terms: D000577:Amides / Q000737:chemistry; D000588:Amines / Q000138:chemical synthesis* / Q000494:pharmacology; D001249:Asthma / Q000188:drug therapy; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D004583:Electrons; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008956:Models, Chemical; D015394:Molecular Structure; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy; D043587:Receptor, Muscarinic M3 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D000588:Amines; D043587:Receptor, Muscarinic M3