Synthesis of phenylisothiourea derivatives as inhibitors of NO production in LPS activated macrophages.

A series of phenylisothioureas were synthesized as inhibitors of NO production in lipopolysaccharide-activated macrophages. We investigated the effect of lipophilic moiety and N- or S-substituents of the phenylisothioureas on the activity. Inhibitory activities of carbazole-linked phenylisothioureas were superior to the corresponding simple phenylisothiourea derivatives. Among these compounds, 12b having N-ethyl and S-isopropyl groups on phenylisothiourea moiety was the most potent in the inhibition of NO production. They inhibited NO production through the suppression of the LPS-induced translocation of p65 subunit of NF-kappaB and the followed suppression of the iNOS protein and mRNA expression.