3'-O-取代的 5-(并三苯-3-基乙炔基)-2'-脱氧尿苷作为蜱传脑炎病毒复制抑制剂。
3'-O-Substituted 5-(perylen-3-ylethynyl)-2'-deoxyuridines as tick-borne encephalitis virus reproduction inhibitors.
机构信息
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, 117997 Moscow, Russia.
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, 117997 Moscow, Russia; Department of Chemistry, Lomonosov Moscow State University, 119991 Moscow, Russia; Institute of Poliomyelitis and Viral Encephalitides, FSBSI Chumakov FSC R&D IBP RAS, 108819 Moscow, Russia.
出版信息
Eur J Med Chem. 2018 Jul 15;155:77-83. doi: 10.1016/j.ejmech.2018.05.040. Epub 2018 May 26.
A series of analogues of potent antiviral perylene nucleoside dUY11 with methylthiomethyl (MTM), azidomethyl (AZM) and HO-C-alkyl-1,2,3-triazol-1,4-diyl groups at 3'-O-position as well as the two products of copper-free alkyne-azide cycloaddition of the AZM derivative were prepared and evaluated against tick-borne encephalitis virus (TBEV). Four compounds (4, 6, 8a, 8b) showed EC ≤ 10 nM, thus appearing the most potent TBEV inhibitors to date. Moreover, these nucleosides have higher lipophilicity (clogP) and increased solubility in aq. DMSO vs. parent compound dUY11.
制备了一系列在 3'-O-位带有甲硫甲基 (MTM)、叠氮甲基 (AZM) 和 HO-C-烷基-1,2,3-三唑-1,4-二基的强效抗病毒并苯核苷 dUY11 类似物，以及该 AZM 衍生物的铜自由炔叠氮环加成的两个产物，并对蜱传脑炎病毒 (TBEV) 进行了评估。四种化合物 (4、6、8a、8b) 表现出 EC≤10nM，因此是迄今为止最有效的 TBEV 抑制剂。此外，与母体化合物 dUY11 相比，这些核苷具有更高的亲脂性 (clogP) 和增加的在 aq. DMSO 中的溶解度。
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