Tetrazole and triazole as bioisosteres of carboxylic acid: Discovery of diketo tetrazoles and diketo triazoles as anti-HCV agents

A series of diketo tetrazoles and diketo triazoles were designed and synthesized as bioisosteres of α,γ-diketo acid, the active site inhibitor of HCV (Hepatitis C virus) polymerase NS5B. Among the synthesized compounds, 4-(4-fluorobenzyloxy)phenyl diketo triazole (30) exhibited anti-HCV activity with an EC50 value of 3.9 μM and an SI value more than 128. The reduction of viral protein and mRNA levels were also validated, supporting the anti-HCV activity of compound 30. These results provide convincing evidence that the diketo tetrazoles and diketo triazoles can be developed as bioisosteres of α,γ-diketo acid to exhibit potent inhibitory activity against HCV.

A series of diketo tetrazoles and diketo triazoles were designed and synthesized as bioisosteres of α,γ-diketo acid. Among them, compound 30 exhibited potent anti-HCV activity with an EC50 value of 3.9 μM and an SI value more than 128. The reduction of viral protein and mRNA levels were also validated.Figure optionsDownload as PowerPoint slide