Design and synthesis of urea and thiourea derivatives and their inhibitory activities on lipopolysaccharide-induced NO production.

Series of ureas and thioureas were designed and synthesized, and their inhibitory activities of NO production in lipopolysaccharide-activated macrophages were evaluated. We found several essential moieties in the structure of the prepared compounds for the activity. Thiourea derivatives revealed higher inhibitory activity than the corresponding urea derivatives. Among these compounds, 7e having carboxymethyl group at N3 position of thiourea was the most potent in the inhibition of NO production. They inhibited NO production through the suppression of iNOS protein and mRNA expression.