Discovery of novel aminothiadiazole amides as selective EP(3) receptor antagonists.
This Letter discloses a series of 2-aminothiadiazole amides as selective EP(3) receptor antagonists. SAR optimization resulted in compounds with excellent functional activity in vitro. In addition, efforts to optimize DMPK properties in the rat are discussed. These efforts have resulted in the identification of potent, selective EP(3) receptor antagonists with excellent DMPK properties suitable for in vivo studies.
Hilfiker
Mark A
MA
Department of Medicinal Chemistry, Metabolic Pathways Center of Excellence for Drug Discovery, GlaxoSmithKline Pharmaceuticals, 709 Swedeland Road, King of Prussia, PA 19406, United States. mark.a.hilfiker@gsk.com
Wang
Ning
N
Hou
Xiaoping
X
Du
Zhimin
Z
Pullen
Mark A
MA
Nord
Melanie
M
Nagilla
Rakesh
R
Fries
Harvey E
HE
Wu
Charlene W
CW
Sulpizio
Anthony C
AC
Jaworski
Jon-Paul
JP
Morrow
Dwight
D
Edwards
Richard M
RM
Jin
Jian
J
D000284:Administration, Oral; D000577:Amides / Q000737:chemistry*; D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004285:Dogs; D015195:Drug Design; D006801:Humans; D008956:Models, Chemical; D015394:Molecular Structure; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D018078:Receptors, Prostaglandin E / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D058308:Receptors, Prostaglandin E, EP3 Subtype; D013329:Structure-Activity Relationship; D013830:Thiadiazoles / Q000737:chemistry*
D000577:Amides; C545647:PTGER3 protein, human; C545649:Ptger3 protein, rat; D018078:Receptors, Prostaglandin E; D058308:Receptors, Prostaglandin E, EP3 Subtype; D013830:Thiadiazoles