Abstract
The identification and evaluation of aryl-[1,4]diazepane ureas as functional antagonists of the chemokine receptor CXCR3 are described. Specific examples exhibit IC(50) values of approximately 60 nM in a calcium mobilization functional assay, and dose-dependently inhibit CXCR3 functional response to CXCL11 (interferon-inducible T-cell alpha chemoattractant/I-TAC) as measured by T-cell chemotaxis, with a potency of approximately 100 nM.
MeSH terms
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Calcium / metabolism
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Cell Line
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Chemistry, Pharmaceutical / methods
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Chemokine CXCL11
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Chemokines, CXC / chemistry
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Chemotaxis
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Dose-Response Relationship, Drug
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Drug Design
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Drug Evaluation, Preclinical
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Electrons
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Humans
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Inflammation
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Inhibitory Concentration 50
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Models, Chemical
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Receptors, CXCR3
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Receptors, Chemokine / antagonists & inhibitors*
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Receptors, Chemokine / chemistry
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Receptors, G-Protein-Coupled / metabolism
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Recombinant Proteins / chemistry
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Stereoisomerism
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T-Lymphocytes / cytology
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Urea / chemistry*
Substances
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CXCL11 protein, human
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CXCR3 protein, human
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Chemokine CXCL11
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Chemokines, CXC
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Receptors, CXCR3
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Receptors, Chemokine
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Receptors, G-Protein-Coupled
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Recombinant Proteins
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Urea
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Calcium