Muscarinic acetylcholine receptor antagonists: SAR and optimization of tyrosine ureas.
SAR exploration of multiple regions of a tyrosine urea template led to the identification of very potent muscarinic acetylcholine receptor antagonists such as 10b with good subtype selectivity for M(3) over M(1). The structure-activity relationships (SAR) and optimization of the tyrosine urea series are described.
Jin
Jian
J
Centers of Excellence for Drug Discovery and Molecular Discovery Research, GlaxoSmithKline, 709 Swedeland Road, King of Prussia, PA 19406, USA. jianjin@unc.edu
Wang
Yonghui
Y
Shi
Dongchuan
D
Wang
Feng
F
Fu
Wei
W
Davis
Roderick S
RS
Jin
Qi
Q
Foley
James J
JJ
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
Busch-Petersen
Jakob
J
D001249:Asthma / Q000188:drug therapy; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D015394:Molecular Structure; D018727:Muscarinic Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000737:chemistry*; D012492:Salts / Q000737:chemistry; D013329:Structure-Activity Relationship; D014443:Tyrosine / Q000737:chemistry*; D014508:Urea / Q000737:chemistry*
D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D012492:Salts; D014443:Tyrosine; D014508:Urea