Discovery of small molecule human C5a receptor antagonists
| Autor: | Simon Barber, John Unitt, David Laughton, Fraser Hunt, Sarah King, Bob Thong, Andrew Baxter, Denise Grice, Alastair J. H. Brown, Garry Pairaudeau, Hitesh J. Sanganee, Richard J. Weaver |
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| Rok vydání: | 2009 |
| Předmět: |
Benzimidazole
Clinical Biochemistry Pharmaceutical Science Biochemistry Formyl peptide receptor 1 Rats Sprague-Dawley Mice Structure-Activity Relationship chemistry.chemical_compound Dogs Drug Discovery Benzene Derivatives Animals Combinatorial Chemistry Techniques Humans Inverse agonist Furans Receptor Receptor Anaphylatoxin C5a Molecular Biology G protein-coupled receptor Molecular Structure Organic Chemistry Stereoisomerism Hit to lead Amides Small molecule In vitro Rats Receptors Complement chemistry Microsomes Liver Molecular Medicine |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 19:1143-1147 |
| ISSN: | 0960-894X |
| Popis: | A novel series of small molecule C5a antagonists is reported. In particular, in vitro metabolic studies and solution based combinatorial synthesis are demonstrated as useful tools for the rapid identification of antagonists with low in vitro clearance. Members of this series specifically inhibited the binding of (125)I-labeled C5a to human recombinant C5a receptor (C5aR). In functional cell assays these compounds displayed surmountable antagonism against C5a and did not demonstrate any detectable agonist activity. |
| Databáze: | OpenAIRE |
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