Anti-inflammatory activity of isoxicam in combination with aspirin orD-propoxyphene

Abstract

Unlike several arylacetic acid derivatives (indomethacin, fenoprofen, ibuprofen, flurbiprofen and naproxen), the anti-arthritic activity of isoxicam is not reduced in the adjuvant-induced polyarthritis assay by the concomitant administration of aspirin or D-propoxyphene.

The Methylation Effect in Medicinal Chemistry

“…Several other anti-inflammatory agents contain isoxazole units, e.g., the oxicam me-too drug isoxicam ( 170 ), which was launched in 1983 by Warner-Lambert laboratories under the name of Pacyl, and the PGHS-2 selective inhibitor valdecoxib ( 153 ) and its prodrug parecoxib ( 171 ) (Dynastat). All of these drugs contain a metabolically soft methyl group at C-5 to improve the stability of the five-membered heteroaromatic ring (Figure ).…”

“…The methylation dramatically affects the metabolic profile 276 by offering an additional labile group for CYP oxidation and avoiding the formation of a hepatotoxic species (165) (Figure 34). Several other anti-inflammatory agents contain isoxazole units, e.g., the oxicam me-too drug isoxicam 283 (170), which was launched in 1983 by Warner-Lambert laboratories under the name of Pacyl, and the PGHS-2 selective inhibitor valdecoxib 284 (153) and its prodrug parecoxib 285 (171) (Dynastat). All of these drugs contain a metabolically soft methyl group at C-5 to improve the stability of the five-membered heteroaromatic ring (Figure 35).…”