A series of 1,2,3-triazolyl 3-hydroxy-quinazoline-2,4(1H,3H)-diones was constructed utilizing Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC) method. The biological significance of the novel synthesized quinazolines was highlighted by evaluating them in vitro for antiviral activity, wherein several compounds exhibited excellent activity specifically against vaccinia and adenovirus. Especially, 24b11 displayed the most potent inhibitory activity against vaccinia with an EC₅₀ value of 1.7μM, which was 15 fold than that of the reference drug Cidofovir (EC₅₀ =25μM). 24b13 was the most potent compound against adenovirus-2 with an EC₅₀ value of 6.2μM, which proved lower than all the reference drugs. Preliminary structure–activity relationships were also discussed. To the best of our knowledge, no data are present in the literature on antiviral activity of 3-hydroxy-quinazoline-2,4(1H,3H)-diones against DNA-viruses. Thus, these findings warrant further investigations (library expansion and compound refinement) on this novel class of antiviral agents.

中文翻译：

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通过“特权支架”提炼方法首次发现新颖的3-羟基喹唑啉-2,4（1H，3H）-二酮类药物作为特异性抗痘苗病毒和腺病毒药物

一系列的1,2,3-三唑基3-羟基喹唑啉-2,4（1H，3H）-二酮是利用Cu（I）催化的叠氮化物-炔烃1,3-偶极环加成（CuAAC）方法构建的。通过在体外评估新型合成的喹唑啉类药物的抗病毒活性，可以突出其生物学意义，其中几种化合物表现出优异的抗牛痘和腺病毒活性。特别是24b11对牛痘的抑制作用最强，EC ₅₀值为1.7μM，是参考药物西多福韦（EC ₅₀ =25μM）的15倍。24b13是具有EC ₅₀的最有效的抗腺病毒2的化合物值6.2μM，证明低于所有参考药物。初步的构效关系也进行了讨论。据我们所知，文献中没有有关3-羟基喹唑啉-2,4（1H，3H）-二酮对DNA病毒的抗病毒活性的数据。因此，这些发现值得对这种新型抗病毒药物进行进一步的研究（文库扩展和化合物改良）。