ONE-POT CASCADE SYNTHESIS OF PYRAZOLE BASED ISOSTERES OF VALDECOXIB BY A [3+2] CYCLOADDITION SEQUENCE AND EVALUATION OF THEIR COX INHIBITORY ACTIVITY

A series of 5-methyl-3,4-diaryl-substituted 1H-pyrazoles, N-isosteres of valdecoxib, was synthesized by a [3+2] cycloaddition/[1,5] sigmatropic rearrangement sequence starting from tosylhydrazine, aryl methyl ketones and terminal aryl alkynes bearing various substituents (H, Me, OMe, F, SO2Me, SO2NH2). New pyrazoles were prepared regioselectively in a one-pot process with moderate-good yields. All compounds were used in in vitro cyclooxygenase (COX) assays to determine inhibitory potency and selectivity to COX-1 and COX-2. In general, these new pyrazoles are characterized by selective COX-2 inhibition activity in a micromolar range.