Potent hFPRL1 (ALXR) agonists as potential anti-inflammatory agents

• Published in: Bioorganic & medicinal chemistry letters Vol. 16; no. 14; pp. 3713 - 3718
• Main Authors: Bürli, Roland W., Xu, Han, Zou, Xiaoming, Muller, Kristine, Golden, Jennifer, Frohn, Mike, Adlam, Matthew, Plant, Matthew H., Wong, Min, McElvain, Michele, Regal, Kelly, Viswanadhan, Vellarkad N., Tagari, Philip, Hungate, Randall
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 15.07.2006; Elsevier
• Subjects: Administration, Oral; ALXR; Animals; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Disease Models, Animal; Dose-Response Relationship, Drug; G-protein-coupled receptor; hFPRL1; Humans; Inflammation; Inflammation - drug therapy; Medical sciences; Mice; Molecular Structure; Pharmacology. Drug treatments; Pyrazolones; Receptors, Formyl Peptide - agonists; Receptors, Lipoxin - agonists; Inflammation; ALXR; hFPRL1; Pyrazolones; G-protein-coupled receptor; Human; Agonist; Rodentia; Antiinflammatory agent; Benzene derivatives; Oral administration; fMLP receptor; In vitro; In vivo; Vertebrata; Chemotherapy; Mammalia; Treatment; Structure activity relation; Mouse; Animal; Affinity; Ureas; Chemical synthesis
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2006.04.068

The discovery of potent agonists for the human formyl-peptide-like 1 receptor (hFPRL1) is reported. Recent studies have indicated that agonizing this receptor may promote resolution of inflammation. Following oral administration, a representative compound showed efficacy in a mouse ear inflammation model. We report the discovery of potent agonists for the human formyl-peptide-like 1 receptor (hFPRL1). These compounds did not act at a closely related receptor denoted human formyl peptide receptor (hFPR) up to 10 μM concentration. Recent studies have indicated that agonizing this receptor may promote resolution of inflammation. In an exploratory study, a novel hFPRL1 agonist showed efficacy in a mouse ear inflammation model following oral administration.