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.
MeSH terms
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Animals
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CHO Cells
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Chemotaxis, Leukocyte / drug effects
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Computer Simulation
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Cricetinae
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Cricetulus
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Drug Evaluation, Preclinical
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ERG1 Potassium Channel
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Ether-A-Go-Go Potassium Channels / antagonists & inhibitors
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Humans
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Indicators and Reagents
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Myotonin-Protein Kinase
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Oxazolidinones / chemical synthesis*
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Oxazolidinones / pharmacology*
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Protein Serine-Threonine Kinases / drug effects
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Receptors, CCR8
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Receptors, Chemokine / antagonists & inhibitors*
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Structure-Activity Relationship
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Th2 Cells / drug effects
Substances
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CCR8 protein, human
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DMPK protein, human
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ERG1 Potassium Channel
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Ether-A-Go-Go Potassium Channels
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Indicators and Reagents
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Oxazolidinones
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Receptors, CCR8
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Receptors, Chemokine
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Myotonin-Protein Kinase
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Protein Serine-Threonine Kinases