Abstract
High-affinity, functionally potent, urea-based antagonists of CCR1 have been discovered. Modulation of PXR transactivation has revealed the selective and orally bioavailable CCR1 antagonist BMS-817399 (29), which entered clinical trials for the treatment of rheumatoid arthritis.
MeSH terms
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Animals
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Arthritis, Rheumatoid / drug therapy*
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Biological Availability
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Clinical Trials, Phase II as Topic
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Drug Discovery*
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Hep G2 Cells
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Humans
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Male
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Microsomes, Liver / metabolism
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Models, Molecular
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Piperidines / metabolism
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Piperidines / pharmacokinetics
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Piperidines / pharmacology*
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Piperidines / therapeutic use
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Pregnane X Receptor
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Protein Conformation
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Receptors, CCR1 / antagonists & inhibitors*
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Receptors, CCR1 / chemistry
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Receptors, CCR1 / metabolism
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Receptors, Steroid / metabolism
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Species Specificity
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Urea / analogs & derivatives*
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Urea / metabolism
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Urea / pharmacokinetics
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Urea / pharmacology
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Urea / therapeutic use
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Valine / analogs & derivatives*
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Valine / metabolism
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Valine / pharmacokinetics
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Valine / pharmacology
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Valine / therapeutic use
Substances
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1-(1-(4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl)-3-methyl-1-oxobutan-2-yl)-3-(2-hydroxy-2-methylpropyl)urea
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Piperidines
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Pregnane X Receptor
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Receptors, CCR1
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Receptors, Steroid
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Urea
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Valine