Synthesis and Antiviral Evaluation of (1,4-Disubstituted-1,2,3-Triazol)-(<i>E</i>)-2-Methyl-but-2-Enyl Nucleoside Phosphonate Prodrugs
oleh: Tuniyazi Abuduaini, Vincent Roy, Julien Marlet, Catherine Gaudy-Graffin, Denys Brand, Cécile Baronti, Franck Touret, Bruno Coutard, Tamara R. McBrayer, Raymond F. Schinazi, Luigi A. Agrofoglio
| Format: | Article |
|---|---|
| Diterbitkan: | MDPI AG 2021-03-01 |
Deskripsi
A series of hitherto unknown (1,4-disubstituted-1,2,3-triazol)-(<i>E</i>)-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 <b>15j</b>, a hexadecyloxypropyl (HDP)/(<i>isopropyloxycarbonyl</i>-oxymethyl)-ester (POC) prodrug, showed activity against HBV in Huh7 cell cultures with 62% inhibition at 10 μM, without significant cytotoxicity (IC<sub>50</sub> = 66.4 μM in HepG2 cells, IC<sub>50</sub> = 43.1 μM in HepG2 cells) at 10 μM.