Bioorganic & medicinal chemistry letters, 2010-01, Vol.20 (2), p.662-664
2010
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Details
- Autor(en) / Beteiligte
- Titel
- Identification of a new class of small molecule C5a receptor antagonists
- Ist Teil von
- Bioorganic & medicinal chemistry letters, 2010-01, Vol.20 (2), p.662-664
- Ort / Verlag
- Amsterdam: Elsevier Ltd
- Erscheinungsjahr
- 2010
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- A new class of potent and selective C5a receptor antagonists was discovered through a hit-to-lead process. C5a is a terminal product of the complement cascade that activates and attracts inflammatory cells including granulocytes, mast cells and macrophages via a specific GPCR, the C5a receptor (C5aR). Inhibition of C5a/C5aR interaction has been shown to be efficacious in several animal models of autoimmune diseases, including RA, SLE and asthma. This account reports the discovery of a new class of C5aR antagonists through high-throughput screening. The lead compounds in this series are selective and block C5a binding, C5a-promoted calcium flux in human neutrophils with nanomolar potency.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0960-894XeISSN: 1464-3405DOI: 10.1016/j.bmcl.2009.11.058Titel-ID: cdi_proquest_miscellaneous_733895274
- Format
- –
- Schlagworte
- Anaphylatoxin, Animals, Anti-inflammation, Autoimmune diseases, Biological and medical sciences, Bones, joints and connective tissue. Antiinflammatory agents, C5a, Cell Line, G-protein coupled receptor, High-Throughput Screening Assays, Humans, Immunomodulators, Medical sciences, Mice, Molecular Conformation, Neutrophils - immunology, Neutrophils - metabolism, Pharmacology. Drug treatments, Protein Binding, Receptor, Anaphylatoxin C5a - antagonists & inhibitors, Receptor, Anaphylatoxin C5a - metabolism, Sulfonamides - chemical synthesis, Sulfonamides - chemistry, Sulfonamides - pharmacology