Abstract
A hit-to-lead optimization process was carried out on the high throughput screening hit compound 1 resulting in the identification of several potent and selective CCR1 receptor antagonists. Compound 37 shows the best overall profile with IC(50) values of <100 nM in binding and functional assays.
MeSH terms
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Calcium / metabolism
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Cell Line
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Cell Movement / drug effects
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Chemokine CCL3 / metabolism
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Chemotaxis / drug effects
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Humans
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Molecular Structure
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Monocytes / cytology
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Monocytes / drug effects
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Monocytes / metabolism
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Piperidines / chemical synthesis
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Piperidines / chemistry*
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Piperidines / pharmacology*
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Receptors, CCR1 / antagonists & inhibitors*
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Structure-Activity Relationship
Substances
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CCL3 protein, human
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Chemokine CCL3
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Piperidines
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Receptors, CCR1
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piperidine
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Calcium