Synthesis of new C5-(1-substituted-1,2,3-triazol-4 or 5-yl)-2′-deoxyuridines and their antiviral evaluation

The synthesis and antiviral evaluation of a series of C5-(1,4- and 1,5-disubstituted-1,2,3-triazolo)-nucleoside derivatives is described. The key steps of this synthesis are regioselective Huisgen’s 1,3-dipolar cycloaddition, using either copper-catalyzed azide-alkyne cycloaddition (CuAAC) or ruthenium-catalyzed azide-alkyne cycloaddition (RuAAC) under microwave activation. Some compounds among the 5a–l series possess activity against herpes simplex viruses 1 and 2, varicella-zoster virus, human cytomegalovirus and vaccinia virus. Their cytostatic activities were determined against murine leukemia cells, human T-lymphocyte cells and cervix carcinoma cells. Compounds were also evaluated on a wide panel of RNA viruses, including Vesicular stomatitis virus, influenza viruses type A (H1N1 and H3N2) and B in MDCK cell cultures, parainfluenza-3 virus, reovirus-1, Sindbis virus and Punta Toro virus in Vero cell cultures and Vesicular stomatitis, Coxsackie B4 and respiratory syncytial virus, with no specific antiviral effect.

Graphical abstractNovel nucleosides were designed and synthesized by [3 + 2] cycloaddition, and showed moderate antiviral activities against several different DNA and RNA viruses. Some cytostatic activities against murine leukemia cells, human T-lymphocyte cells and cervix carcinoma cells were found.Figure optionsDownload full-size imageDownload as PowerPoint slideResearch highlights► Synthesis and antiviral evaluation of new of C5-(1,4- and 1,5-disubstituted-1,2,3-triazolo)-nucleoside derivatives. ► Regioselective Huisgen’s 1,3-dipolar cycloaddition, using either copper-catalyzed azide-alkyne cycloaddition (CuAAC) or ruthenium-catalyzed azide-alkyne cycloaddition (RuAAC) under microwave activation. ► In situ generation of phenyl azides to access small librairies. ► Antiviral activity (μM range) of several compounds against herpes simplex viruses 1 and 2, varicella-zoster virus, human cytomegalovirus and vaccinia virus. ► Compounds were also evaluated on a wide panel of other viral strains.