Stable ester and amide conjugates of some NSAIDs as analgesic and antiinflammatory compounds with improved biological activity

摘要

A set of ester and amide derivatives of some acidic NSAIDs,including ibuprofen, ketoprofen, and mefenamic acid (1-3), weresynthesized and evaluated for their in vivo analgesic andantiinflammatory activity using the p-benzoquinone-induced writhingtest and the carrageenan-induced paw edema model, respectively. Amongthe synthesized compounds, ester derivatives of ketoprofen showedespecially potent analgesic and antiinflammatory activity as comparedto the parent drug. In vitro chemical stability studies revealed thatester and amide derivatives were chemically stable in simulatedgastric (pH 1.2) and intestinal fluids (pH 6.8). In 80% humanplasma, the ester derivatives were found to be relatively stableagainst plasma esterases over periods of 24 h, indicating that theobserved activity was not due to the parent NSAIDs. Most of thecompounds were found to be nonulcerogenic under the tested conditions.