Abstract
Interleukin-8 modulation is implicated in many inflammatory and cancer diseases. Starting from a mass-screening hit, the synthesis and structure-activity relationship of 2-amino-3-heteroarylquinoxalines as non-peptide, small molecule interleukine-8 receptor antagonists have been developed. The optimized derivatives, PD 0210293 (13y) and PD 0220245 (13r), show inhibition of both IL-8 receptor binding and IL-8-mediated neutrophil chemotaxis.
MeSH terms
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Anti-Inflammatory Agents / chemistry
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Antineoplastic Agents / chemistry
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Calcium / metabolism
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Chemotaxis / drug effects
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Diamines / chemical synthesis
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Diamines / chemistry
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Diamines / pharmacology
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Humans
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Quinoxalines* / chemical synthesis
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Quinoxalines* / chemistry
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Quinoxalines* / pharmacology
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Receptors, Interleukin-8A / antagonists & inhibitors*
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Receptors, Interleukin-8A / metabolism
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Structure-Activity Relationship
Substances
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Anti-Inflammatory Agents
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Antineoplastic Agents
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Diamines
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Quinoxalines
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Receptors, Interleukin-8A
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Calcium