title: Core exploration in optimization of chemokine receptor CCR4 antagonists.
abstract: 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).
authors.affiliation: Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543, USA. ashok.purandare@bms.com
authors.forename: Ashok V
authors.initials: AV
authors.lastname: Purandare
authors.forename: Honghe
authors.initials: H
authors.lastname: Wan
authors.forename: John E
authors.initials: JE
authors.lastname: Somerville
authors.forename: Christine
authors.initials: C
authors.lastname: Burke
authors.forename: Wayne
authors.initials: W
authors.lastname: Vaccaro
authors.forename: XiaoXia
authors.initials: X
authors.lastname: Yang
authors.forename: Kim W
authors.initials: KW
authors.lastname: McIntyre
authors.forename: Michael A
authors.initials: MA
authors.lastname: Poss
mesh_terms: 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
chemical_list: D001593:Benzyl Compounds; C515355:Ccr4 protein, mouse; D007202:Indicators and Reagents; D011804:Quinolines; D054398:Receptors, CCR4; D019707:Receptors, Chemokine; D010047:Ovalbumin