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

• Published in: Molecules (Basel, Switzerland) Vol. 26; no. 5; p. 1493
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 09.03.2021; MDPI
• Subjects: Alkenes - chemistry; Animals; Antiviral Agents - chemical synthesis; Antiviral Agents - pharmacology; antiviral properties; Azo Compounds - chemistry; Binding sites; Cell Line, Tumor; Chemical compounds; Chlorocebus aethiops; Chromatography; copper-catalyzed azide-alkyne cycloaddition (CuAAC); Cytomegalovirus; Cytotoxicity; Drugs; HBV; Hepatitis; Hepatitis B virus - drug effects; HIV; HIV-1 - drug effects; Human health and pathology; Human immunodeficiency virus; Humans; Infectious diseases; Life Sciences; Magnetic Resonance Spectroscopy; Medication; Metathesis; Methylation; Nucleosides; Nucleosides - chemistry; olefin cross metathesis; Organophosphonates - chemistry; Pharmaceutical sciences; Phosphonates; Prodrugs; Prodrugs - chemical synthesis; Prodrugs - pharmacology; SARS-CoV-2 - drug effects; Severe acute respiratory syndrome coronavirus 2; Structure-Activity Relationship; Triazoles - chemistry; ultrasound; Vero Cells; Viruses; SARS-CoV-2; nucleosides; antiviral properties; HIV; olefin cross metathesis; HBV; copper-catalyzed azide-alkyne cycloaddition (CuAAC); ultrasound; copper-catalyzed azide-alkyne cycloaddition (CuAAC
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules26051493

A series of hitherto unknown (1,4-disubstituted-1,2,3-triazol)-( )-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 , a hexadecyloxypropyl (HDP)/( -oxymethyl)-ester (POC) prodrug, showed activity against HBV in Huh7 cell cultures with 62% inhibition at 10 μM, without significant cytotoxicity (IC = 66.4 μM in HepG2 cells, IC = 43.1 μM in HepG2 cells) at 10 μM.