Fused heterocyclic amido compounds as anti-hepatitis C virus agents

We identified a fused heteroaromatic amido structure based on the phenanthridine skeleton as a superior scaffold for candidate drugs with potent anti-HCV activity. Among the compounds synthesized, a phenanthridine analogue with a 1,3-dioxolyl group (24) possessed the most potent anti-HCV activity (EC50 value: 50 nM), with acceptable cytotoxicity. The structural development and structure–activity relationships of these compounds are described.

A series of phenanthridine analogues were synthesized and evaluated for their anti-hepatitis C virus (HCV) activity. Among the compounds alkoxylated analogues 18 and 24 showed significant inhibition against HCV RNA replication with an EC50 values of 180, 50 nM, respectively. In addition, they had acceptable cytotoxicities resulting in high SI values, 42 and 128, respectively.Figure optionsDownload as PowerPoint slide