Studies on antiinflammatory agents. III. Synthesis and pharmacological properties of metabolites of 4'-acetyl-2'-(2,4-difluorophenoxy)methanesulfonanilide (FK3311).

We synthesized putative metabolites of 4'-acetyl-2'-(2,4-difluorophenoxy)methanesulfonanilide (FK3311, 1), a novel antiinflammatory agent, in order to confirm their structures and also to investigate their pharmacological properties. The structures of the metabolites 2-5 were confirmed by direct comparison with the synthesized authentic compounds. We employed the following tests to assess pharmacological activities: zymosan-induced prostaglandin E2 production for in vitro activity, adjuvant-induced arthritis for antiinflammatory activity, and acetic acid-induced writhing for analgesic activity. Metabolite 2 is nearly equipotent to 1 in the in vivo tests and metabolite 3 is an active metabolite with in vitro activity comparable to that of 1.