First discovery of novel 3-hydroxy-quinazoline-2,4(1H,3H)-diones as specific anti-vaccinia and adenovirus agents via 'privileged scaffold' refining approach.
First discovery of novel 3-hydroxy-quinazoline-2,4(1H,3H)-diones as specific anti-vaccinia and adenovirus agents via 'privileged scaffold' refining approach.
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DOI：
10.1016/j.bmcl.2016.09.071
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发表时间：
2016-11-01
影响因子：
2.7
通讯作者：
Liu X
中科院分区：
文献类型：
--
作者：
Kang D;Zhang H;Zhou Z;Huang B;Naesens L;Zhan P;Liu X
首次发现新型3-羟基-喹唑啉-2，4（1H，3 H）-二酮作为特异性抗牛痘和腺病毒剂。 24 b11对牛痘病毒的抑制活性最强，EC 50值为1.7 μM。 24 b13是针对腺病毒-2最有效的化合物，EC 50值为6.2 μM。这些新的类似物的初步SAR进行了详细说明。利用Cu（I）催化的叠氮-炔1，3-偶极环加成反应（CuAAC）合成了一系列1，2，3-三唑基-3-羟基喹唑啉-2，4（1H，3 H）-二酮化合物。新合成的喹唑啉类的生物学意义通过体外评价它们的抗病毒活性来突出，其中几种化合物表现出特异性抗牛痘和腺病毒的优异活性。特别是，24 b11对牛痘表现出最强的抑制活性，EC 50值为1.7 μM，是参比药物西多福韦（EC 50 = 25 μM）的15倍。24 b13是抗腺病毒-2的最有效化合物，其EC 50值为6.2 μM，证明低于所有参比药物。初步的构效关系进行了讨论。据我们所知，文献中没有关于3-羟基-喹唑啉-2，4（1H，3 H）-二酮抗DNA病毒的抗病毒活性的数据。因此，这些发现保证了对这类新型抗病毒剂的进一步研究（文库扩增和化合物精制）。
First discovery of novel 3-hydroxy-quinazoline-2,4(1H,3H)-diones as specific anti-vaccinia and adenovirus agents. 24b11 displayed the most potent inhibitory activity against vaccinia with an EC50 value of 1.7 μM. 24b13 was the most potent compound against adenovirus-2 with an EC50 value of 6.2 μM. Preliminary SARs of these novel analogues were detailed. 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 1.7 μM, which was 15 fold than that of the reference drug Cidofovir (EC50 = 25 μM). 24b13 was the most potent compound against adenovirus-2 with an EC50 value of 6.2 μM, 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.
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影响因子：
4
作者：
Desimmie, Belete A.;Demeulemeester, Jonas;Christ, Frauke
通讯作者：
Christ, Frauke
影响因子：
11.8
作者：
Bray, M;Buller, M
通讯作者：
Buller, M
DOI：
10.1164/ajrccm.157.2.9608057
发表时间：
1998-02-01
影响因子：
24.7
作者：
Klinger, JR;Sanchez, MP;Matyas, B
通讯作者：
Matyas, B
影响因子：
2.7
作者：
ADRIAN, T;WADELL, G;WIGAND, R
通讯作者：
WIGAND, R
影响因子：
2.7
作者：
Suchaud, Virginie;Bailly, Fabrice;Cotelle, Philippe
通讯作者：
Cotelle, Philippe