Abstract
We describe the synthesis and SAR of a new class of CCR2 antagonists based on 2-mercaptoimidazole scaffold. The initial lead 1a was optimized to the 3,4-disubstituted analogues 1p-(S) and 1q-(S), which have IC(50) values in the MCP-1 induced Ca-flux below 0.01 microM.
MeSH terms
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Calcium Signaling / drug effects
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Cell Line
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Chemokine CCL2 / pharmacology
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Ethylenethiourea* / analogs & derivatives*
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Ethylenethiourea* / chemical synthesis*
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Ethylenethiourea* / pharmacology*
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Humans
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Imidazoles / chemical synthesis
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Imidazoles / pharmacology
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Inhibitory Concentration 50
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Receptors, CCR2
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Receptors, Chemokine / antagonists & inhibitors*
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Structure-Activity Relationship
Substances
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CCL2 protein, human
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CCR2 protein, human
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Chemokine CCL2
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Imidazoles
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Receptors, CCR2
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Receptors, Chemokine
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Ethylenethiourea
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2-mercaptoimidazole