Synthesis of sulfamoylbenzamide derivatives as HBV capsid assembly effector.
Synthesis of sulfamoylbenzamide derivatives as HBV capsid assembly effector.
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DOI：
10.1016/j.ejmech.2017.06.062
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发表时间：
2017-09-29
影响因子：
6.7
通讯作者：
Schinazi RF
中科院分区：
文献类型：
--
作者：
Sari O;Boucle S;Cox BD;Ozturk T;Russell OO;Bassit L;Amblard F;Schinazi RF
报道了作为 HBV 衣壳组装效应物的新型氨磺酰苯甲酰胺系列的合成。该结构分为五个部分，作为我们先导化合物优化的一部分，这些部分被独立修改。所有合成的化合物均在人肝细胞、淋巴细胞和其他细胞中评估其抗乙肝病毒活性和毒性。此外，我们还在基于 HBeAg 报告细胞的测定中评估了它们对 HBV cccDNA 形成的影响。在报道的 27 种化合物中，几种类似物表现出亚微摩尔活性并显着减少 HBeAg 分泌。在负染色电子显微镜下研究了所选化合物破坏 HBV 衣壳形成的能力。将结构建模为最近在 HBV 衣壳蛋白中发现的类似分子的结合位点，以合理化该化合物家族的结构-活性关系。
The synthesis of novel series of sulfamoylbenzamides as HBV capsid assembly effector is reported. The structure was divided into five parts which were independently modified as part of our lead optimization. All synthesized compounds were evaluated for their anti-HBV activity and toxicity in human hepatocytes, lymphocytes and other cells. Additionally, we assessed their effect on HBV cccDNA formation in an HBeAg reporter cell-based assay. Among the 27 compounds reported, several analogs exhibited submicromolar activities and significant reduction of HBeAg secretion. Selected compounds were studied under negative-stain electron microscopy for their ability to disrupt the HBV capsid formation. Structures were modeled into a binding site recently identified in the HBV capsid protein for similar molecules to rationalize the structure-activity relationships for this family of compounds.
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DOI：
10.3390/ijerph120810039
发表时间：
2015-08-21
影响因子：
--
作者：
Wei W;Wu Q;Zhou J;Kong Y;You H
通讯作者：
You H
影响因子：
4.6
作者：
Zhou Z;Hu T;Zhou X;Wildum S;Garcia-Alcalde F;Xu Z;Wu D;Mao Y;Tian X;Zhou Y;Shen F;Zhang Z;Tang G;Najera I;Yang G;Shen HC;Young JA;Qin N
通讯作者：
Qin N
影响因子：
5.1
作者：
Boucle S;Bassit L;Ehteshami M;Schinazi RF
通讯作者：
Schinazi RF
影响因子：
4
作者：
Katen, Sarah P.;Chirapu, Srinivas Reddy;Finn, M. G.;Zlotnick, Adam
通讯作者：
Zlotnick, Adam
影响因子：
4.9
作者：
Cai, Dawei;Mills, Courtney;Guo, Haitao
通讯作者：
Guo, Haitao