Substituted 5-benzyl-2-phenyl-5H-imidazo[4,5-c]pyridines represent a novel class of compounds with activity against pestiviruses and the hepatitis C virus (HCV). Several series of analogues with modifications of the substituents in positions 2 and 5 were prepared. These efforts resulted in the discovery of several compounds with potent antiviral activity of which 2-(2,3-difluorophenyl)-5-[4-(trifluoromethyl)benzyl]-5H-imidazo[4,5-c]pyridine (46) was most potent against HCV (EC(50) of 0.10 microM and a selectivity index of 1080).