Unsymmetrical non-adamantyl N,N′-diaryl urea and amide inhibitors of soluble expoxide hydrolase

We explored replacement of an adamantyl R group in the aryl ether scaffold 1 with substituted aryl rings to identify equipotent, and metabolically stable sEH inhibitors. We found that aryl rings, especially those substituted in the para position with a strongly electron withdrawing substituent, afforded comparable enzyme potency.