| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1372284 | Bioorganic & Medicinal Chemistry Letters | 2013 | 4 Pages |
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.
Graphical abstractA 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 full-size imageDownload as PowerPoint slide
