A novel influenza virus neuraminidase inhibitor AV5027
A novel influenza virus neuraminidase inhibitor AV5027
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DOI：
10.1016/j.antiviral.2013.10.008
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发表时间：
2013-12-01
影响因子：
7.6
通讯作者：
Borisova, Olga V.
中科院分区：
文献类型：
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作者：
Ivachtchenko, Alexandre V.;Ivanenkov, Yan A.;Borisova, Olga V.
采用组合方法成功合成了一个中等规模的具有抗病毒活性的新型奥司他韦结构类似物库。然后在基于神经氨酸酶和细胞的测定中对合成的化合物进行彻底评估。结果表明，（3R，4 R，5S）-4-（2，2-二氟乙酰氨基）-5-氨基-3-（1-乙基-丙氧基）-环己-1-烯羧酸（AV 5027）被鉴定为具有皮摩尔效价的新型HIT-化合物。基于获得的生物学数据进行QSAR分析。使用3D分子对接方法和经典回归分析进行计算建模。所开发的积分模型证明了足够的预测准确性和耐受性，以基于化合物至少在支架内对神经氨酸酶（NA）的潜在活性来评价化合物。该系列中的几种化合物可以被合理地视为有前途的抗流感候选药物。由爱思唯尔公司出版
A medium-sized focused library of novel Oseltamivir structural analogues with promising antiviral activity was successfully synthesized using a combinatorial approach. The synthesized compounds were then thoroughly evaluated in neuraminidase- and cell-based assays. As a result, (3R,4R,5S)-4-(2,2-difluoroacetylamino)-5-amino-3-(1-ethyl-propoxy)-cyclohex-1-enecarboxylic acid (AV5027) was identified as novel Hit-compound with picomolar potency. QSAR analysis was carried out based on the obtained biological data. Computational modeling was performed using a 3D-molecular docking approach and classical regression analysis. The developed integral model demonstrated a sufficient prediction accuracy and tolerance to evaluate compounds based on their potential activity against neuraminidase (NA) at least within the scaffold. Several compounds from the series can be reasonably regarded as promising anti-influenza drug-candidates. Published by Elsevier B.V.