Replacement of the carboxylic acid functionality of select heterocycles converted this cyclooxygenase (CO) inhibitor into blipoxygenase (540). meclofenamic acid with dual inhibitors of CO and The anti-inflammatory agent meclofenamic acid, 1, belongs to the fenamate (N-arylanthranilic acid) class of non-steroidal anti-inflammatory drugs (NSAIDs)l. NSAlDs reduce the pain and swelling associated with arthritis by blocking the metabolism of arachidonic acid by the enzyme cyclooxygenase (CO) and thereby the production of prostaglandins. An undesirable side effect of the chronic use of NSAlDs is the formation of gastric ulcer@. This adverse event may be minimized in the presence of an inhibitor of 5-lipoxygenase @-LO), another enzyme in the arachidonic acid cascade. Several dual inhibitors of CO and 5-LO are currently under investigation for the treatment of arthritiss.We recently reported that replacing the carboxylic acid functionality of meclofenamic acid with a heterocycle incorporated 5-lipoxygenase inhibitory activity into the NSAID pharmacophore. The heterocycles described previously were 1,3,4-oxadiazole-2-thiones or 1,3,4-thiadiazole-2 thionesb. We now report the preparation and in vitro evaluation of meclofenamic acid analogs where a rhodanine derivative is attached to the fenamate core via a double bond.