Synthesis and antiallergic activities of 1,3-oxazolo[4,5-h]quinolines
| Autor: | John H. Musser, S. Sciortino, Mitchell J. Leibowitz, P. Sonnino-Goldman, Kevin Bailey, Atul Khandwala, Howard Jones, Stephen M. Coutts, Edward S. Neiss, P. S. Wolf |
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| Rok vydání: | 1985 |
| Předmět: |
Chemical Phenomena
Stereochemistry Pharmacology Immunoglobulin E Histamine Release Structure-Activity Relationship chemistry.chemical_compound Cromolyn Sodium Drug Discovery Animals Structure–activity relationship Mast Cells Oxazoles IC50 ED50 biology Passive Cutaneous Anaphylaxis Biological activity In vitro Rats Chemistry chemistry Quinolines biology.protein Molecular Medicine Histamine |
| Zdroj: | Journal of Medicinal Chemistry. 28:1255-1259 |
| ISSN: | 1520-4804 0022-2623 |
| Popis: | A series of new 1,3-oxazolo[4,5-h]quinolines has been prepared. These compounds were tested as inhibitors of antigen-induced release of histamine (AIR) in vitro from rat peritoneal mast cells (RMC) and as inhibitors of IgE-mediated passive cutaneous anaphylaxis in the rat (PCA). After several modifications of the original lead, the most potent compound of the series was determined to be 5-chloro-1,3-oxazolo[4,5-h]quinoline-2-carboxylic acid methyl ester (4a). It has an IC50 of 0.3 microM in the RMC assay and an ED50 (intraperitoneal) of 0.1 mg/kg in the PCA test, which is 10 times and 60 times more potent than disodium cromoglycate (DSCG), respectively. Of greater importance, it is orally active (ED50 = 0.5 mg/kg) as an inhibitor of the PCA test. |
| Databáze: | OpenAIRE |
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