2-Aminomethyl piperidines as novel urotensin-II receptor antagonists.
A series of 2-aminomethyl piperidines has been discovered as novel urotensin-II receptor antagonists. The synthesis, initial structure-activity relationships, and optimization of the initial hit that resulted in the identification of potent, cross-species active, and functional urotensin-II receptor antagonists such as 1a and 11a are described.
Jin
Jian
J
Cardiovascular and Urogenital Center of Excellence for Drug Discovery, GlaxoSmithKline, 709 Swedeland Road, King of Prussia, PA 19406, USA. jian.jin@gsk.com
Wang
Yonghui
Y
Wang
Feng
F
Shi
Dongchuan
D
Erhard
Karl F
KF
Wu
Zining
Z
Guida
Brian F
BF
Lawrence
Sarah K
SK
Behm
David J
DJ
Disa
Jyoti
J
Vaidya
Kalindi S
KS
Evans
Christopher
C
McMillan
Lynette J
LJ
Rivero
Ralph A
RA
Neeb
Michael J
MJ
Douglas
Stephen A
SA
D001665:Binding Sites; D006801:Humans; D008744:Methylamines / Q000138:chemical synthesis / Q000494:pharmacology*; D008956:Models, Chemical; D010880:Piperidines / Q000138:chemical synthesis / Q000494:pharmacology*; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014662:Vasoconstrictor Agents / Q000138:chemical synthesis / Q000494:pharmacology*
D008744:Methylamines; D010880:Piperidines; D043562:Receptors, G-Protein-Coupled; C121697:UTS2R protein, human; D014662:Vasoconstrictor Agents