Abstract
A series of leflunomide (1a) analogues were examined for antiinflammatory activity using the carrageenan-induced paw edema assay. Some of the compounds were significantly more potent than leflunomide, particularly those with electron-donating or negative inductive groups situated in the phenyl rings. In contrast, all the nonsubstituted compounds or with further chain-extension in the 4-position of the rings led to a decrease in activity. The LD(50) values of the most active compounds (1d, g-j) in male ICR mice were significantly greater than those of either 1a or its active metabolite 2 and therefore merit further study.
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