title: Oxazolidinones as novel human CCR8 antagonists.
abstract: High-throughput screening of the corporate compound collection led to the discovery of a novel series of N-substituted-5-aryl-oxazolidinones as potent human CCR8 antagonists. The synthesis, structure-activity relationships, and optimization of the series that led to the identification of SB-649701 (1a), are described.
authors.affiliation: Discovery Medicinal Chemistry, Molecular Discovery Research, GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, PA 19426, USA. jian.jin@gsk.com
authors.forename: Jian
authors.initials: J
authors.lastname: Jin
authors.forename: Yonghui
authors.initials: Y
authors.lastname: Wang
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.forename: Jeffery K
authors.initials: JK
authors.lastname: Kerns
authors.forename: Victoria M
authors.initials: VM
authors.lastname: Vinader
authors.forename: Ashley P
authors.initials: AP
authors.lastname: Hancock
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Lindon
authors.forename: Graeme I
authors.initials: GI
authors.lastname: Stevenson
authors.forename: Dwight M
authors.initials: DM
authors.lastname: Morrow
authors.forename: Parvathi
authors.initials: P
authors.lastname: Rao
authors.forename: Cuc
authors.initials: C
authors.lastname: Nguyen
authors.forename: Victoria J
authors.initials: VJ
authors.lastname: Barrett
authors.forename: Chris
authors.initials: C
authors.lastname: Browning
authors.forename: Guido
authors.initials: G
authors.lastname: Hartmann
authors.forename: David P
authors.initials: DP
authors.lastname: Andrew
authors.forename: Henry M
authors.initials: HM
authors.lastname: Sarau
authors.forename: James J
authors.initials: JJ
authors.lastname: Foley
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Jurewicz
authors.forename: James A
authors.initials: JA
authors.lastname: Fornwald
authors.forename: Andy J
authors.initials: AJ
authors.lastname: Harker
authors.forename: Michael L
authors.initials: ML
authors.lastname: Moore
authors.forename: Ralph A
authors.initials: RA
authors.lastname: Rivero
authors.forename: Kristen E
authors.initials: KE
authors.lastname: Belmonte
authors.forename: Helen E
authors.initials: HE
authors.lastname: Connor
mesh_terms: D000818:Animals; D016466:CHO Cells; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003198:Computer Simulation; D006224:Cricetinae; D003412:Cricetulus; D004353:Drug Evaluation, Preclinical; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors; D006801:Humans; D007202:Indicators and Reagents; D065636:Myotonin-Protein Kinase; D023303:Oxazolidinones / Q000138:chemical synthesis* / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects; D054401:Receptors, CCR8; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D018418:Th2 Cells / Q000187:drug effects
chemical_list: C103330:CCR8 protein, human; C585517:DMPK protein, human; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D007202:Indicators and Reagents; D023303:Oxazolidinones; D054401:Receptors, CCR8; D019707:Receptors, Chemokine; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases