Chromatographic resolution, chiroptical characterization and preliminary pharmacological evaluation of the enantiomers of butibufen: a comparison with ibuprofen.

Enantiomeric resolution of butibufen has been achieved on a cellulose tris(3,5-dimethylphenylcarbamate) chiral stationary phase with hexane-isopropanol-trifluoroacetic acid, 100:1.2:0.02 (v/v/v) as mobile phase at a flow rate of 1.0 mL min(-1). Semi-preparative isolation of the enantiomers then chiroptical characterization indicated that the order of elution was (-)-R- before (+)-S-butibufen. When tested for their effects on the cyclooxygenase and 5-lipoxygenase pathways of eicosanoid metabolism in calcium ionophore-activated rat peritoneal leukocytes it was found that (+)-S-butibufen inhibited generation of thromboxane B2 (TXB2) and prostaglandin E2 (PGE2) (cyclooxygenase pathway), with an IC50 of 1.5 microM (approx.), whereas the (-)-R enantiomer was essentially inactive. Neither enantiomer inhibited the 5-lipoxygenase pathway. In this regard, (+)-S-butibufen was approximately five times less potent as a cyclooxygenase inhibitor than (+)-S-ibuprofen. These results show the enantiomeric specificity and pathway selectivity of this novel non-steroidal anti-inflammatory drug.