Abstract
N,N'-Diarylureas were prepared, and the structure-activity relationship relative to the CXCR2 receptor was examined. This led to the identification of a potent and highly selective CXCR2 antagonist, which in addition was shown to be functionally active both in vitro against human neutrophils and in vivo in rabbit models of ear edema and neutropenia.
MeSH terms
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Animals
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Anti-Inflammatory Agents / chemical synthesis*
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Anti-Inflammatory Agents / chemistry
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Anti-Inflammatory Agents / pharmacology
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Binding, Competitive
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CHO Cells
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Calcium / metabolism
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Chemokine CXCL1
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Chemokines
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Chemotactic Factors
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Chemotaxis
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Cricetinae
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Humans
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Hypersensitivity, Delayed / chemically induced
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Hypersensitivity, Delayed / drug therapy
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In Vitro Techniques
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Intercellular Signaling Peptides and Proteins
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Interleukin-8
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Neutropenia / chemically induced
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Neutropenia / drug therapy
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Neutrophils / drug effects
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Neutrophils / metabolism
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Neutrophils / physiology
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Phenylurea Compounds / chemical synthesis*
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Phenylurea Compounds / chemistry
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Phenylurea Compounds / pharmacology
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Rabbits
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Radioligand Assay
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Receptors, Interleukin-8A / antagonists & inhibitors
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Receptors, Interleukin-8A / metabolism
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Receptors, Interleukin-8B / antagonists & inhibitors*
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Receptors, Interleukin-8B / metabolism
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Structure-Activity Relationship
Substances
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Anti-Inflammatory Agents
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CXCL1 protein, Bos taurus
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Chemokine CXCL1
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Chemokines
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Chemotactic Factors
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Intercellular Signaling Peptides and Proteins
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Interleukin-8
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N-(3-bromo-4-cyano-2-hydroxyphenyl)-N'-(2-bromophenyl)urea
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Phenylurea Compounds
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Receptors, Interleukin-8A
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Receptors, Interleukin-8B
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Calcium