Details

Autor(en) / Beteiligte

• Proskurin, Gleb V.
• Orlov, Alexey A.
• Brylev, Vladimir A.
• Kozlovskaya, Liubov I.
• Chistov, Alexey A.
• Karganova, Galina G.
• Palyulin, Vladimir A.
• Osolodkin, Dmitry I.
• Korshun, Vladimir A.
• Aralov, Andrey V.

Titel

3′-O-Substituted 5-(perylen-3-ylethynyl)-2′-deoxyuridines as tick-borne encephalitis virus reproduction inhibitors

Ist Teil von

• European journal of medicinal chemistry, 2018-07, Vol.155, p.77-83

Ort / Verlag

France: Elsevier Masson SAS

Erscheinungsjahr

2018

Quelle

Elsevier ScienceDirect Journals

Beschreibungen/Notizen

• A series of analogues of potent antiviral perylene nucleoside dUY11 with methylthiomethyl (MTM), azidomethyl (AZM) and HO-C1–4-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 EC50 ≤ 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. A series of 3′-O-derivatives of antiviral perylene nucleoside dUY11 were prepared using ‘click’ chemistry and showed high activity against tick-borne encephalitis virus (TBEV). [Display omitted] •3′-O-Azidomethyl-5-(perylen-3-ylethynyl)deoxyuridine was prepared and functionalized further using ‘click’ chemistry.•Four 3′-O-derivatives showed enhanced activity against tick-borne encephalitis virus (TBEV).•The anti-TBEV activity of compounds somewhat correlates with their lipophilicity.•The most active compounds showed better solubility in water–DMSO.