Synthesis and Anti-HCV Activity of 4‑Hydroxyamino α‑Pyranone Carboxamide Analogues

High genetic variability in hepatitis C virus (HCV), emergence of drug resistant viruses and side effects demand the requirement for development of new scaffolds to show an alternate mechanism. Herein, we report discovery of new scaffold I based on 4-hydroxyamino α-pyranone carboxamide as promising anti-HCV agents. A comprehensive structure–activity relationship (SAR) was explored with several newly synthesized compounds. In all promising compounds (17–19, 21–22, 24–25, and 49) with EC50 ranging 0.15 to 0.40 μM, the aryl group at C-6 position of α-pyranone were unsubstituted. In particular, 25 demonstrated potential anti-HCV activity with EC50 of 0.18 μM in cell based HCV replicon system with lower cytotoxicity (CC50 > 20 μM) and provided a new scaffold for anti-HCV drug development. Further investigations, including biochemical characterization, are yet to be performed to elucidate its possible mode of action.