Kuznetsov Nikolai Yu, Tikhov Rabdan M, Godovikov Ivan A, Medvedev Michael G, Lyssenko Konstantin A, Burtseva Elena I, Kirillova Elena S, Bubnov Yuri N
A.N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Vavilov 28, 119991, Moscow, Russian Federation.
N.F. Gamaleya Institute of Epidemiology and Microbiology, Russian Academy of Medicinal Sciences, Gamaleya 18, 123098, Moscow, Russian Federation.
Org Biomol Chem. 2017 Apr 11;15(15):3152-3157. doi: 10.1039/c7ob00331e.
A series of (R)- and (S)-isomers of new adamantane-substituted heterocycles (1,3-oxazinan-2-one, piperidine-2,4-dione, piperidine-2-one and piperidine) with potent activity against rimantadine-resistant strains of influenza A virus were synthesized through the transformation of adamantyl-substituted N-Boc-homoallylamines 8 into piperidine-2,4-diones 11 through the cyclic bromourethanes 9 and key intermediate enol esters 10. Biological assays of the prepared compounds were performed on the rimantadine-resistant S31N mutated strains of influenza A - A/California/7/2009(H1N1)pdm09 and modern pandemic strain A/IIV-Orenburg/29-L/2016(H1N1)pdm09. The most potent compounds were both enantiomers of the enol ester 10 displaying IC = 7.7 μM with the 2016 Orenburg strain.
通过将金刚烷基取代的N - Boc - 高烯丙基胺8经环溴代脲烷9和关键中间体烯醇酯10转化为哌啶 - 2,4 - 二酮11，合成了一系列对甲型流感病毒金刚烷胺耐药株具有强效活性的新型金刚烷取代杂环化合物（1,3 - 恶嗪烷 - 2 - 酮、哌啶 - 2,4 - 二酮、哌啶 - 2 - 酮和哌啶）的（R） - 和（S） - 异构体。对制备的化合物进行了生物学测定，测试对象为甲型流感病毒的金刚烷胺耐药S31N突变株——A/California/7/2009(H1N1)pdm09以及现代大流行株A/IIV - Orenburg/29 - L/2016(H1N1)pdm09。最具活性的化合物是烯醇酯10的两种对映体，对2016年奥伦堡毒株的IC₅₀ = 7.7 μM。
