Core exploration in optimization of chemokine receptor CCR4 antagonists.
The design, synthesis, and SAR studies of 'core' variations led to identification of novel, selective, and potent small molecule antagonist (22) of the CC chemokine receptor-4 (CCR4) with improved in vitro activity and liability profile. Compound 22 was efficacious in a murine allergic inflammation model (ED50 approximately 10 mg/kg).
Purandare
Ashok V
AV
Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543, USA. ashok.purandare@bms.com
Wan
Honghe
H
Somerville
John E
JE
Burke
Christine
C
Vaccaro
Wayne
W
Yang
XiaoXia
X
McIntyre
Kim W
KW
Poss
Michael A
MA
D000818:Animals; D001593:Benzyl Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D002460:Cell Line; D002633:Chemotaxis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007202:Indicators and Reagents; D051379:Mice; D010047:Ovalbumin; D011014:Pneumonia / Q000139:chemically induced / Q000188:drug therapy; D011804:Quinolines / Q000138:chemical synthesis / Q000494:pharmacology; D054398:Receptors, CCR4; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors*; D012130:Respiratory Hypersensitivity / Q000188:drug therapy / Q000473:pathology; D013329:Structure-Activity Relationship
D001593:Benzyl Compounds; C515355:Ccr4 protein, mouse; D007202:Indicators and Reagents; D011804:Quinolines; D054398:Receptors, CCR4; D019707:Receptors, Chemokine; D010047:Ovalbumin