775344-76-8Relevant academic research and scientific papers
Novel synthesis of 3,4-diarylisoxazole analogues of valdecoxib: Reversal cyclooxygenase-2 selectivity by sulfonamide group removal
Di Nunno, Leonardo,Vitale, Paola,Scilimati, Antonio,Tacconelli, Stefania,Patrignani, Paola
, p. 4881 - 4890 (2004)
3,4-Diarylisoxazole analogues of valdecoxib [4-(5-methyl-3-phenylisoxazol- 4-yl)-benzensulfonamide], a selective cyclooxygenase-2 (COX-2) inhibitor, were synthesized by 1,3-dipolar cycloaddition of arylnitrile oxides to the enolate ion of phenylacetone regioselectively prepared in situ with lithium diisopropylamide at 0 °C. The corresponding 3-aryl-5-methyl-4-phenyl- isoxazoles were easily generated by a dehydration/aromatization reaction under basic conditions of 3-aryl-5-hydroxy-5-methyl-4-phenyl-2-isoxazolines and further transformed into their benzenesulfonamide derivatives. The biochemical COX-1/COX-2 selectivity was evaluated in vitro by using the human whole blood assays of COX isozyme activity. Three compounds not bearing the sulfonamide group present in valdecoxib were selective COX-1 inhibitors.
ISOXAZOLE DERIVATIVES AND THEIR USE AS CYCLOOXYGENASE INHIBITORS
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Page/Page column 10; 13, (2010/02/13)
The present invention refers to isoxazole derivatives, in particular 3,4-diaryl isoxazole derivatives, to their pharmaceutical compositions, the process for preparing them and their use as inhibitors of cycloosygenase, in particular of cycloosygenase 1 and 2 (COX-1) (COX-2). The present invention also refers to a process for determining the potential toxicity of compounds that inhibit cycloosygenase (COX), in particular cycloosygenase-2 (COX-2) isoform, and to the use of compounds that inhibit cycloosygenase (COX), in particular cycloosygenase-2 (COX-2) and their pharmaceutical compositions, in subjects for whom the potential cardiovascular toxicity of said compounds is reduced.
