Synthesis and SAR of a new series of COX-2-selective inhibitors: pyrazolo[1,5-a]pyrimidines
| Autor: | Manuel Merlos, Julian Garcia-Rafanell, F. L. Cavalcanti, J. Forn, de Arriba Af, C. Almansa, L. A. Gomez, Agusti Miralles |
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| Rok vydání: | 2001 |
| Předmět: |
Male
Pyrimidine Stereochemistry Carrageenan Chemical synthesis Pyrazolopyrimidine Sulfone Cell Line Rats Sprague-Dawley chemistry.chemical_compound Structure-Activity Relationship In vivo Drug Discovery Animals Edema Humans Enzyme Inhibitors Bicyclic molecule biology Anti-Inflammatory Agents Non-Steroidal Stomach Membrane Proteins Biological activity Exudates and Transudates Combinatorial chemistry Rats Isoenzymes Pyrimidines chemistry Enzyme inhibitor Cyclooxygenase 2 Prostaglandin-Endoperoxide Synthases Rats Inbred Lew biology.protein Cyclooxygenase 1 Molecular Medicine Pyrazoles |
| Zdroj: | Journal of medicinal chemistry. 44(3) |
| ISSN: | 0022-2623 |
| Popis: | The synthesis and pharmacological activity of a series of bicyclic pyrazolo[1,5-a]pyrimidines as potent and selective cyclooxygenase-2 (COX-2) inhibitors are described. The new compounds were evaluated both in vitro (COX-1 and COX-2 inhibition in human whole blood) and in vivo (carrageenan-induced paw edema and air-pouch model). Modification of the pyrimidine substituents showed that 6,7-disubstitution provided the best activity and led to the identification of 3-(4-fluorophenyl)-6,7-dimethyl-2-(4-methylsulfonylphenyl)pyrazolo[1,5-a]pyrimidine (10f) as one of the most potent and selective COX-2 inhibitor in this series. |
| Databáze: | OpenAIRE |
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