Abstract
DPC168, a benzylpiperidine-substituted aryl urea CCR3 antagonist evaluated in clinical trials, was a relatively potent inhibitor of the 2D6 isoform of cytochrome P-450 (CYP2D6). Replacement of the cyclohexyl central ring with saturated heterocycles provided potent CCR3 antagonists with improved selectivity against CYP2D6. The favorable preclinical profile of DPC168 was maintained in an acetylpiperidine derivative, BMS-570520.
MeSH terms
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Animals
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Benzyl Compounds / chemical synthesis
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Benzyl Compounds / chemistry*
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Benzyl Compounds / pharmacology*
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Biological Assay
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Cells, Cultured
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Cytochrome P-450 CYP2D6 Inhibitors*
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Humans
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Mice
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Pan troglodytes
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Phenylurea Compounds / chemistry*
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Phenylurea Compounds / pharmacology
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Piperidines / chemical synthesis
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Piperidines / chemistry*
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Piperidines / pharmacology*
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Receptors, CCR3
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Receptors, Chemokine / antagonists & inhibitors*
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Structure-Activity Relationship
Substances
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1-(2-((3-(4-fluorobenzyl)piperidin-1-yl)methyl)cyclohexyl)-3-(3-acetylphenyl)urea
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BMS-570520
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Benzyl Compounds
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CCR3 protein, human
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Ccr3 protein, mouse
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Cytochrome P-450 CYP2D6 Inhibitors
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Phenylurea Compounds
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Piperidines
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Receptors, CCR3
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Receptors, Chemokine