Structure-activity relationship of biaryl acylsulfonamide analogues on the human EP(3) prostanoid receptor.
Potent and selective ligands for the human EP3 prostanoid receptor are described. Biaryl compounds bearing a tethered ortho substituted acidic moiety were identified as potent EP3 antagonists based on the SAR described herein. The binding affinity of key compounds on all eight human prostanoid receptors is reported.
Merck Frosst Centre for Therapeutic Research, PO Box 1005, Pointe Claire-Dorval, H9R 4P8, Québec, Canada. michel_gallant@merck.com
M
M
Gallant
M C
MC
Carrière
A
A
Chateauneuf
D
D
Denis
Y
Y
Gareau
C
C
Godbout
G
G
Greig
H
H
Juteau
N
N
Lachance
P
P
Lacombe
S
S
Lamontagne
K M
KM
Metters
C
C
Rochette
R
R
Ruel
D
D
Slipetz
N
N
Sawyer
N
N
Tremblay
M
M
Labelle
D006801:Humans; D018078:Receptors, Prostaglandin E / Q000187:drug effects*; D058308:Receptors, Prostaglandin E, EP3 Subtype; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry* / Q000494:pharmacology*
C545647:PTGER3 protein, human; D018078:Receptors, Prostaglandin E; D058308:Receptors, Prostaglandin E, EP3 Subtype; D013449:Sulfonamides