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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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
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author 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.
author_facet 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.
author_sort Abuduaini, Tuniyazi
collection PubMed
description 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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spelling pubmed-79671602021-03-18 Synthesis and Antiviral Evaluation of (1,4-Disubstituted-1,2,3-Triazol)-(E)-2-Methyl-but-2-Enyl Nucleoside Phosphonate Prodrugs 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. Molecules Article 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. MDPI 2021-03-09 /pmc/articles/PMC7967160/ /pubmed/33803417 http://dx.doi.org/10.3390/molecules26051493 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
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.
Synthesis and Antiviral Evaluation of (1,4-Disubstituted-1,2,3-Triazol)-(E)-2-Methyl-but-2-Enyl Nucleoside Phosphonate Prodrugs
title Synthesis and Antiviral Evaluation of (1,4-Disubstituted-1,2,3-Triazol)-(E)-2-Methyl-but-2-Enyl Nucleoside Phosphonate Prodrugs
title_full Synthesis and Antiviral Evaluation of (1,4-Disubstituted-1,2,3-Triazol)-(E)-2-Methyl-but-2-Enyl Nucleoside Phosphonate Prodrugs
title_fullStr Synthesis and Antiviral Evaluation of (1,4-Disubstituted-1,2,3-Triazol)-(E)-2-Methyl-but-2-Enyl Nucleoside Phosphonate Prodrugs
title_full_unstemmed Synthesis and Antiviral Evaluation of (1,4-Disubstituted-1,2,3-Triazol)-(E)-2-Methyl-but-2-Enyl Nucleoside Phosphonate Prodrugs
title_short Synthesis and Antiviral Evaluation of (1,4-Disubstituted-1,2,3-Triazol)-(E)-2-Methyl-but-2-Enyl Nucleoside Phosphonate Prodrugs
title_sort synthesis and antiviral evaluation of (1,4-disubstituted-1,2,3-triazol)-(e)-2-methyl-but-2-enyl nucleoside phosphonate prodrugs
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967160/
https://www.ncbi.nlm.nih.gov/pubmed/33803417
http://dx.doi.org/10.3390/molecules26051493
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