Structure-activity relationships and pharmacokinetic parameters of quinoline acylsulfonamides as potent and selective antagonists of the EP(4) receptor.
A new series of EP(4) antagonists based on a quinoline acylsulfonamide scaffold have been identified as part of our on-going efforts to develop treatments for chronic inflammation. These compounds show subnanomolar intrinsic binding potency towards the EP(4) receptor, and excellent selectivity towards other prostanoid receptors. Acceptable pharmacokinetic profiles have also been demonstrated across a series of preclinical species.
Burch
Jason D
JD
Merck Frosst Centre for Therapeutic Research, 16711 Trans-Canada Highway, Kirkland, Que., Canada H9H 3L1. jason_burch@merck.com
Belley
Michel
M
Fortin
Réjean
R
Deschênes
Denis
D
Girard
Mario
M
Colucci
John
J
Farand
Julie
J
Therien
Alex G
AG
Mathieu
Marie-Claude
MC
Denis
Danielle
D
Vigneault
Erika
E
Lévesque
Jean-François
JF
Gagné
Sébastien
S
Wrona
Mark
M
Xu
Daigen
D
Clark
Patsy
P
Rowland
Steve
S
Han
Yongxin
Y
D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D004285:Dogs; D006168:Guinea Pigs; D006801:Humans; D008253:Macaca mulatta; D015394:Molecular Structure; D011804:Quinolines / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D018078:Receptors, Prostaglandin E / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D058309:Receptors, Prostaglandin E, EP4 Subtype; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*
C545650:PTGER4 protein, human; D011804:Quinolines; D018078:Receptors, Prostaglandin E; D058309:Receptors, Prostaglandin E, EP4 Subtype; D013449:Sulfonamides