Synthesis and SAR of pyridothiazole substituted pyrimidine derived HCV replication inhibitors.

Abstract Introduction of a nitrogen atom into the benzene ring of a previously identified HCV replication (replicase) benzothiazole inhibitor 1 , resulted in the discovery of the more potent pyridothiazole analogues 3 . The potency and PK properties of the compounds were attenuated by the introductions of various functionalities at the R 1 , R 2 or R 3 positions of the molecule (compound 3 ). Inhibitors 38 and 44 displayed excellent potency, selectivity (GAPDH/MTS CC 50 ), PK parameters in all species studied, and cross genotype activity.