Discovery and SAR of trisubstituted thiazolidinones as CCR4 antagonists.
Substituted thiazolidinones were identified as CCR4 antagonists from high throughput screening. Subsequent lead optimization efforts resulted in defined structure-activity relationships and the identification of potent antagonists (compounds 90 and 91) that inhibited the chemotaxis of Th2 T-cells in vitro.
Allen
Shelley
S
Array BioPharma, 3200 Walnut Street, Boulder, CO 80301, USA.
Newhouse
Bradley
B
Anderson
Aaron S
AS
Fauber
Benjamin
B
Allen
Andrew
A
Chantry
David
D
Eberhardt
Christine
C
Odingo
Joshua
J
Burgess
Laurence E
LE
D000818:Animals; D051379:Mice; D011485:Protein Binding / Q000502:physiology; D054398:Receptors, CCR4; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D045162:Thiazolidinediones / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology
C515355:Ccr4 protein, mouse; D054398:Receptors, CCR4; D019707:Receptors, Chemokine; D045162:Thiazolidinediones