四唑和三唑作为羧酸的生物等排体：二酮四唑和二酮三唑作为抗 HCV 药物的发现。
Tetrazole and triazole as bioisosteres of carboxylic acid: discovery of diketo tetrazoles and diketo triazoles as anti-HCV agents.
机构信息
Key Laboratory of Medical Molecular Virology, Shanghai Medical College, Fudan University, 138 Yi-Xue-Yuan Road, Shanghai 200032, PR China.
出版信息
Bioorg Med Chem Lett. 2013 Aug 15;23(16):4528-31. doi: 10.1016/j.bmcl.2013.06.045. Epub 2013 Jun 26.
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.
一系列的二酮四唑和二酮三唑被设计并合成出来，作为 HCV（丙型肝炎病毒）聚合酶 NS5B 的活性位点抑制剂 α,γ-二酮酸的生物等排体。在所合成的化合物中，4-(4-氟苄氧基)苯基二酮三唑（30）表现出抗 HCV 活性，EC50 值为 3.9 μM，SI 值大于 128。病毒蛋白和 mRNA 水平的降低也得到了验证，支持化合物 30 的抗 HCV 活性。这些结果提供了令人信服的证据，证明二酮四唑和二酮三唑可以作为 α,γ-二酮酸的生物等排体来开发，以表现出对 HCV 的强大抑制活性。
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