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.