Synthesis and Antiviral Evaluation of (1,4-Disubstituted-1,2,3-Triazol)-(E)-2-Methyl-but-2-Enyl Nucleoside Phosphonate Prodrugs

A series of hitherto unknown (1,4-disubstituted-1,2,3-triazol)-(E)-2-methyl-but-2-enyl nucleosides phosphonate prodrugs bearing 4-substituted-1,2,3-triazoles were prepared in a straight approach through an olefin acyclic cross metathesis as the key synthetic step. All novel compounds were evaluated...

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Detalles Bibliográficos
Autores principales: Abuduaini, Tuniyazi, Roy, Vincent, Marlet, Julien, Gaudy-Graffin, Catherine, Brand, Denys, Baronti, Cécile, Touret, Franck, Coutard, Bruno, McBrayer, Tamara R., Schinazi, Raymond F., Agrofoglio, Luigi A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967160/
https://www.ncbi.nlm.nih.gov/pubmed/33803417
http://dx.doi.org/10.3390/molecules26051493
Descripción
Sumario:A series of hitherto unknown (1,4-disubstituted-1,2,3-triazol)-(E)-2-methyl-but-2-enyl nucleosides phosphonate prodrugs bearing 4-substituted-1,2,3-triazoles were prepared in a straight approach through an olefin acyclic cross metathesis as the key synthetic step. All novel compounds were evaluated for their antiviral activities against HBV, HIV and SARS-CoV-2. Among these molecules, only compound 15j, a hexadecyloxypropyl (HDP)/(isopropyloxycarbonyl-oxymethyl)-ester (POC) prodrug, showed activity against HBV in Huh7 cell cultures with 62% inhibition at 10 μM, without significant cytotoxicity (IC(50) = 66.4 μM in HepG2 cells, IC(50) = 43.1 μM in HepG2 cells) at 10 μM.

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