Tetrazole and triazole as bioisosteres of carboxylic acid: discovery of diketo tetrazoles and diketo triazoles as anti-HCV agents
- PMID: 23856047
- DOI: 10.1016/j.bmcl.2013.06.045
Tetrazole and triazole as bioisosteres of carboxylic acid: discovery of diketo tetrazoles and diketo triazoles as anti-HCV agents
Abstract
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.
Keywords: Anti-HCV activity; Bioisosteres; Diketo tetrazoles; Diketo triazoles.
Copyright © 2013 Elsevier Ltd. All rights reserved.
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