Evaluation of Potent and Selective Small-Molecule Antagonists for the CXCR2 Chemokine Receptor

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...

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Bibliographic Details
Published in:Journal of medicinal chemistry 2004-03, Vol.47 (6), p.1319-1321
Main Authors: Widdowson, Katherine L, Elliott, John D, Veber, Daniel F, Nie, Hong, Rutledge, Melvin C, McCleland, Brent W, Xiang, Jia-Ning, Jurewicz, Anthony J, Hertzberg, Robert P, Foley, James J, Griswold, Don E, Martin, Lenox, Lee, Judithann M, White, John R, Sarau, Henry M
Format: Article
Language:English
Subjects:
Animals
Anti-Inflammatory Agents - chemical synthesis
Anti-Inflammatory Agents - chemistry
Anti-Inflammatory Agents - pharmacology
Binding, Competitive
Biological and medical sciences
Bones, joints and connective tissue. Antiinflammatory agents
Calcium - metabolism
Chemokine CXCL1
Chemokines
Chemotactic Factors
Chemotaxis
CHO Cells
Cricetinae
Humans
Hypersensitivity, Delayed - chemically induced
Hypersensitivity, Delayed - drug therapy
In Vitro Techniques
Intercellular Signaling Peptides and Proteins
Interleukin-8
Medical sciences
Neutropenia - chemically induced
Neutropenia - drug therapy
Neutrophils - drug effects
Neutrophils - metabolism
Neutrophils - physiology
Pharmacology. Drug treatments
Phenylurea Compounds - chemical synthesis
Phenylurea Compounds - chemistry
Phenylurea Compounds - pharmacology
Rabbits
Radioligand Assay
Receptors, Interleukin-8A - antagonists & inhibitors
Receptors, Interleukin-8A - metabolism
Receptors, Interleukin-8B - antagonists & inhibitors
Receptors, Interleukin-8B - metabolism
Structure-Activity Relationship
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Summary: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.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm034248l