1,5-Biaryl pyrrole derivatives as EP1 receptor antagonists: Structure–activity relationships of 4- and 5-substituted benzoic acid derivatives
| Autor: | Gerard Martin Paul Giblin, Anton D. Michel, Adrian Hall, Riccardo Novelli, Matthew R. Johnson, Alan Naylor, Susan H. Brown, David J. Spalding, Nicholas Maughan Clayton, Mark Patrick Healy, Anita Chowdhury, Jennifer Sweeting, Iain P. Chessell, Tanya Coleman, Beverley Hammond, Ann Metcalf |
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| Rok vydání: | 2007 |
| Předmět: |
Stereochemistry
Clinical Biochemistry Pain Pharmaceutical Science CHO Cells Benzoates Biochemistry Chemical synthesis Structure-Activity Relationship chemistry.chemical_compound Cricetulus In vivo Oral administration Cricetinae mental disorders Drug Discovery Animals Receptors Prostaglandin E Structure–activity relationship Pyrroles Receptor Molecular Biology Benzoic acid Pyrrole Inflammation Organic Chemistry Antagonist Receptors Prostaglandin E EP1 Subtype Rats chemistry Molecular Medicine |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 17:732-735 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2006.10.078 |
| Popis: | This paper details the SAR of 1,5-biaryl pyrrole derivatives with substituents in the 2-, 4-, and 5-positions of the benzoic acid group as EP1 receptor antagonists. Substitution at the 2-position was poorly tolerated, whereas only fluorine was tolerated at the 4-position. In contrast, a range of substituents at the 5-position were discovered which enhanced the in vitro affinity and led to compounds with promising oral exposure. Three derivatives showed efficacy in a preclinical model of inflammatory pain when dosed orally to rats. |
| Databáze: | OpenAIRE |
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