Urotensin-II receptor antagonists: synthesis and SAR of N-cyclic azaalkyl benzamides.
SAR exploration of the central diamine, benzyl, and terminal aminoalkoxy regions of the N-cyclic azaalkyl benzamide series led to the identification of very potent human urotensin-II receptor antagonists such as 1a with a K(i) of 4 nM. The synthesis and structure-activity relationships (SAR) of N-cyclic azaalkyl benzamides are described.
Centers of Excellence for Drug Discovery, GlaxoSmithKline, 709 Swedeland Road, King of Prussia, PA 19406, USA. jian.jin@gsk.com
Jian
J
Jin
Ming
M
An
Anthony
A
Sapienza
Nambi
N
Aiyar
Diane
D
Naselsky
Henry M
HM
Sarau
James J
JJ
Foley
Kevin L
KL
Salyers
Steven D
SD
Knight
Richard M
RM
Keenan
Ralph A
RA
Rivero
Dashyant
D
Dhanak
Stephen A
SA
Douglas
D001549:Benzamides / Q000737:chemistry*; D001665:Binding Sites; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003959:Diamines / Q000737:chemistry; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008956:Models, Chemical; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D001549:Benzamides; D003959:Diamines; D043562:Receptors, G-Protein-Coupled; C121697:UTS2R protein, human