Oxazolidinones as novel human CCR8 antagonists.
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.
Jin
Jian
J
Discovery Medicinal Chemistry, Molecular Discovery Research, GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, PA 19426, USA. jian.jin@gsk.com
Wang
Yonghui
Y
Wang
Feng
F
Kerns
Jeffery K
JK
Vinader
Victoria M
VM
Hancock
Ashley P
AP
Lindon
Matthew J
MJ
Stevenson
Graeme I
GI
Morrow
Dwight M
DM
Rao
Parvathi
P
Nguyen
Cuc
C
Barrett
Victoria J
VJ
Browning
Chris
C
Hartmann
Guido
G
Andrew
David P
DP
Sarau
Henry M
HM
Foley
James J
JJ
Jurewicz
Anthony J
AJ
Fornwald
James A
JA
Harker
Andy J
AJ
Moore
Michael L
ML
Rivero
Ralph A
RA
Belmonte
Kristen E
KE
Connor
Helen E
HE
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
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