Optimization of CCR4 antagonists: side-chain exploration.
The design, synthesis, and activity of novel and selective small molecule antagonists of the CC chemokine receptor-4 (CCR4) are presented. Compound 8c was efficacious in a murine allergic inflammation model (ED(50) 30 mg/kg).
Purandare
Ashok V
AV
Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543, USA. ashok.purandare@bms.com
Wan
Honghe
H
Gao
Aiming
A
Somerville
John
J
Burke
Christine
C
Vaccaro
Wayne
W
Yang
Xiaoxia
X
McIntyre
Kim W
KW
Poss
Michael A
MA
D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods; D018925:Chemokines / Q000378:metabolism; D002633:Chemotaxis; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004804:Eosinophils / Q000378:metabolism; D006967:Hypersensitivity; D007249:Inflammation; D020128:Inhibitory Concentration 50; D007962:Leukocytes / Q000166:cytology; D051379:Mice; D008956:Models, Chemical; D054398:Receptors, CCR4; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors*; D015398:Signal Transduction; D013329:Structure-Activity Relationship
C515355:Ccr4 protein, mouse; D018925:Chemokines; D054398:Receptors, CCR4; D019707:Receptors, Chemokine