PSI-6206 (RO2433) is the unphosphorylated parent compound of triphosphate analog PSI-7409, which is a potent inhibitor of the HCV NS5B RNA dependent RNA polymerase. The monophosphate form of PSI-6206 was shown to be metabolized in primary human hepatocytes to its triphosphate analog PSI-7409. Furthermore, the phosphoramidate prodrug of PSI-6206 monophosphate, PSI-7851, was developed. Alternatively, PSI-6130, an aminated analog of PSI-6206 monophosphate, was also developed. (1,2,3)

PSI-7409, the triphosphate of PSI-6206 inhibits wild-type and S282T HCV RdRp with Ki values of 0.42 and 22 uM, respectively. PSI-7851, the phosphoramidate of PSI-6206 monophosphate, showed an EC50 value of 1.62 uM for inhibiting HCV RNA replication. (2)