3′-O-Substituted 5-(perylen-3-ylethynyl)-2′-deoxyuridines as tick-borne encephalitis virus reproduction inhibitors
Proskurin G. V., Orlov A. A., Brylev V. A., Kozlovskaya L. I., Chistov A. A., Karganova G. G., Palyulin V. A., Osolodkin D. I., Korshun V. A., Aralov A. V.
European Journal of Medicinal Chemistry
Vol.155, P. 77-83
Опубликовано: 2018
Тип ресурса: Статья
DOI:10.1016/j.ejmech.2018.05.040
Аннотация:
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. © 2018 Elsevier Masson SAS
Ключевые слова:
Antiviral activity; Cycloaddition; Lipophilicity; Nucleoside; Tick-borne encephalitis virus
3' o azidomethyl 5 (perylen 3 ylethynyl) 2' deoxyuridine; 3' o methylthiomethyl 5 (perylen 3 ylethynyl) 2' deoxyuridine; 3' o [4 (2 hydroxyethyl) 1,2,3 triazol 1 ylmethyl] 5 (perylen 3 ylethynyl) 2' deoxyuridine; 3' o [4 (3 hydroxypropyl) 1,2,3 triazol 1 ylmethyl] 5 (perylen 3 ylethynyl) 2' deoxyuridine; 3' o [4 (4 hydroxybutyl) 1,2,3 triazol 1 ylmethyl] 5 (perylen 3 ylethynyl) 2' deoxyuridine; 3' o [4 hydroxymethyl 1,2,3 triazol 1 ylmethyl] 5 (perylen 3 ylethynyl) 2' deoxyuridine; 5 (perylen 3 ylethynyl) 3' deoxyuridine; 5' o (triisopropylsilyl) 3' o azidomethyl 5 (perylen 3 ylethynyl) 2' deoxyuridine; 5' o (triisopropylsilyl) 3' o methylthiomethyl 5 (perylen 3 ylethynyl) 2' deoxyuridine; 5' o (triisopropylsilyl) 5 (perylen 3 ylethynyl) 2' deoxyuridine; alkyne; azide; azidomethyl; carbohydrate derivative; deoxyuridine derivative; dimethyl sulfoxide; duy 11; methylthiomethyl; perylene; reagent; unclassified drug; virus fusion inhibitor; antivirus agent; deoxyuridine; antiviral activity
Язык текста: Английский
ISSN: 1768-3254
Proskurin G. V.
Orlov A. A. Anton Anatolyevich 1991-
Brylev V. A.
Kozlovskaya L. I. Lyubov` Igorevna 1984-
Chistov A. A.
Karganova G. G. Galina Grigoryevna 1956-
Palyulin V. A.
Osolodkin D. I. Dmitrij Ivanovich 1985-
Korshun V. A.
Aralov A. V.
Проскурин Г. В.
Орлов А. А. Антон Анатольевич 1991-
Брyлев В. А.
Козловская Л. И. Любовь Игоревна 1984-
Чистов А. А.
Карганова Г. Г. Галина Григорьевна 1956-
Палюлин В. А.
Осолодкин Д. И. Дмитрий Иванович 1985-
Коршун В. А.
Аралов А. В.
3′-O-Substituted 5-(perylen-3-ylethynyl)-2′-deoxyuridines as tick-borne encephalitis virus reproduction inhibitors
Текст визуальный непосредственный
European Journal of Medicinal Chemistry
Elsevier Science Publisher B.V.
Vol.155 P. 77-83
2018
Статья
Antiviral activity Cycloaddition Lipophilicity Nucleoside Tick-borne encephalitis virus
3' o azidomethyl 5 (perylen 3 ylethynyl) 2' deoxyuridine 3' o methylthiomethyl 5 (perylen 3 ylethynyl) 2' deoxyuridine 3' o [4 (2 hydroxyethyl) 1,2,3 triazol 1 ylmethyl] 5 (perylen 3 ylethynyl) 2' deoxyuridine 3' o [4 (3 hydroxypropyl) 1,2,3 triazol 1 ylmethyl] 5 (perylen 3 ylethynyl) 2' deoxyuridine 3' o [4 (4 hydroxybutyl) 1,2,3 triazol 1 ylmethyl] 5 (perylen 3 ylethynyl) 2' deoxyuridine 3' o [4 hydroxymethyl 1,2,3 triazol 1 ylmethyl] 5 (perylen 3 ylethynyl) 2' deoxyuridine 5 (perylen 3 ylethynyl) 3' deoxyuridine 5' o (triisopropylsilyl) 3' o azidomethyl 5 (perylen 3 ylethynyl) 2' deoxyuridine 5' o (triisopropylsilyl) 3' o methylthiomethyl 5 (perylen 3 ylethynyl) 2' deoxyuridine 5' o (triisopropylsilyl) 5 (perylen 3 ylethynyl) 2' deoxyuridine alkyne azide azidomethyl carbohydrate derivative deoxyuridine derivative dimethyl sulfoxide duy 11 methylthiomethyl perylene reagent unclassified drug virus fusion inhibitor antivirus agent deoxyuridine antiviral activity
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. © 2018 Elsevier Masson SAS