Literature DB >> 33803417

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

Tuniyazi Abuduaini1, Vincent Roy1, Julien Marlet2, Catherine Gaudy-Graffin2, Denys Brand2, Cécile Baronti3, Franck Touret3, Bruno Coutard3, Tamara R McBrayer4, Raymond F Schinazi4, Luigi A Agrofoglio1.   

Abstract

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 (IC50 = 66.4 μM in HepG2 cells, IC50 = 43.1 μM in HepG2 cells) at 10 μM.

Entities:  

Keywords:  HBV; HIV; SARS-CoV-2; antiviral properties; copper-catalyzed azide-alkyne cycloaddition (CuAAC); nucleosides; olefin cross metathesis; ultrasound

Mesh：

Substances：

Year:  2021        PMID： 33803417      PMCID： PMC7967160          DOI： 10.3390/molecules26051493

Source DB:  PubMed          Journal:  Molecules        ISSN： 1420-3049            Impact factor:   4.411


  22 in total

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6.  Peptidotriazoles on solid phase: [1,2,3]-triazoles by regiospecific copper(i)-catalyzed 1,3-dipolar cycloadditions of terminal alkynes to azides.

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Review 9.  Cu(I)-catalyzed Huisgen azide-alkyne 1,3-dipolar cycloaddition reaction in nucleoside, nucleotide, and oligonucleotide chemistry.

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  2 in total

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