Wang Mengmeng, Srivastava Puneet, Liu Chao, Snoeck Robert, Andrei Graciela, De Jonghe Steven, Herdewijn Piet
Medicinal Chemistry, Rega Institute for Medical Research, KU Leuven, Herestraat 49, 3000, Leuven, Belgium.
Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, KU Leuven, Herestraat 49, 3000, Leuven, Belgium.
Eur J Med Chem. 2018 Apr 25;150:616-625. doi: 10.1016/j.ejmech.2018.03.008. Epub 2018 Mar 10.
The synthesis of both 2'-hydroxy-3'-deoxy and 2'-deoxy-3'-hydroxy cyclopentyl nucleoside phosphonates with the natural nucleobases adenine, thymine, cytosine and guanine from a single precursor has been performed. The guanine containing analogues showed antiviral activity. Especially the 3'-deoxy congener 23 was active, displaying an EC of 5.35 μM against TK VZV strain and an EC of 8.83 μM against TK VZV strain, besides lacking cytotoxicity. However, the application of phosphonodiamidate prodrug strategy did not lead to a boost in antiviral activity.
已经从单一前体合成了具有天然核碱基腺嘌呤、胸腺嘧啶、胞嘧啶和鸟嘌呤的2'-羟基-3'-脱氧和2'-脱氧-3'-羟基环戊基核苷膦酸酯。含鸟嘌呤的类似物显示出抗病毒活性。特别是3'-脱氧同系物23具有活性，对TK VZV菌株的EC50为5.35μM，对TK VZV菌株的EC50为8.83μM，此外还没有细胞毒性。然而，膦二酰胺前药策略的应用并没有导致抗病毒活性的提高。
