（1,4-二取代-1,2,3-三唑基）-()-2-甲基-2-丁烯基核苷膦酸酯前药的合成与抗病毒活性评价。
Synthesis and Antiviral Evaluation of (1,4-Disubstituted-1,2,3-Triazol)-()-2-Methyl-but-2-Enyl Nucleoside Phosphonate Prodrugs.
机构信息
Institute of Organic and Analytical Chemistry, CNRS UMR 7311, Universite d'Orléans, F-45067 Orléans, France.
Inserm U1259, Université de Tours, 37032 Tours, France.
出版信息
Molecules. 2021 Mar 9;26(5):1493. doi: 10.3390/molecules26051493.
A series of hitherto unknown (1,4-disubstituted-1,2,3-triazol)-()-2-methyl-but-2-enyl nucleosides phosphonate prodrugs bearing 4-substituted-1,2,3-triazoles were prepared in a straight approach through an olefin acyclic cross metathesis as the key synthetic step. All novel compounds were evaluated for their antiviral activities against HBV, HIV and SARS-CoV-2. Among these molecules, only compound , a hexadecyloxypropyl (HDP)/(-oxymethyl)-ester (POC) prodrug, showed activity against HBV in Huh7 cell cultures with 62% inhibition at 10 μM, without significant cytotoxicity (IC = 66.4 μM in HepG2 cells, IC = 43.1 μM in HepG2 cells) at 10 μM.
一系列 hitherto unknown (1,4-disubstituted-1,2,3-triazol)-()-2-methyl-but-2-enyl nucleosides phosphonate prodrugs 带有 4-substituted-1,2,3-triazoles，通过非环烯烃交叉复分解反应作为关键合成步骤，直接制备。所有新化合物都针对 HBV、HIV 和 SARS-CoV-2 的抗病毒活性进行了评估。在这些分子中，只有化合物 ，一种十六烷氧基丙基（HDP）/（-甲氧基）-酯（POC）前药，在 Huh7 细胞培养物中对 HBV 表现出活性，在 10 μM 时抑制率为 62%，而在 10 μM 时对 HepG2 细胞（IC = 66.4 μM）和 HepG2 细胞（IC = 43.1 μM）的细胞毒性没有显著影响。
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