M3 muscarinic acetylcholine receptor antagonists: SAR and optimization of bi-aryl amines.
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.
Budzik
Brian
B
Centers of Excellence for Drug Discovery, GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, PA 19426, USA.
Wang
Yonghui
Y
Shi
Dongchuan
D
Wang
Feng
F
Xie
Haibo
H
Wan
Zehong
Z
Zhu
Chongye
C
Foley
James J
JJ
Nuthulaganti
Parvathi
P
Kallal
Lorena A
LA
Sarau
Henry M
HM
Morrow
Dwight M
DM
Moore
Michael L
ML
Rivero
Ralph A
RA
Palovich
Michael
M
Salmon
Michael
M
Belmonte
Kristen E
KE
Laine
Dramane I
DI
Jin
Jian
J
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
D000577:Amides; D000588:Amines; D043587:Receptor, Muscarinic M3