四唑和三唑作为羧酸生物等电体：四唑二酮和三唑二酮作为抗HCV药物的发现
etrazole and triazole as bioisosteres of carboxylic acid: discovery of diketo tetrazoles and diketo triazoles as anti-HCV agents
本课题设计了一系列二酮四唑和二酮三唑类化合物，作为丙型肝炎病毒（HCV）聚合酶NS5B的活性位点抑制剂的α,γ-二酮酸的生物电子等排体。在合成的化合物中，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水平的降低也得到验证，可作为化合物30具有抗HCV活性的有力证据。这些结果表明，二酮四唑和二酮三唑可以作为α,γ-二酮酸的生物电子等排体显示出对HCV的有效抑制活性。
In this paper, 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, supportingthe 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.
叶徳泳、袁正宏、刘明明、宋武慧、钟东威、周璐
药学基础医学生物化学
药物化学抗HCV活性二酮四唑二酮三唑生物电子等排
anti-HCV activitydiketo tetrazolesdiketo triazolesbioisosteres
叶徳泳,袁正宏,刘明明,宋武慧,钟东威,周璐.四唑和三唑作为羧酸生物等电体：四唑二酮和三唑二酮作为抗HCV药物的发现[EB/OL].(2017-05-05)[2025-08-10].http://www.paper.edu.cn/releasepaper/content/201705-449.点此复制
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