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

被引：7

作者：

Abuduaini, Tuniyazi ^{[1
]}

Roy, Vincent ^{[1
]}

Marlet, Julien ^{[2
]}

Gaudy-Graffin, Catherine ^{[2
]}

Brand, Denys ^{[2
]}

Baronti, Cecile ^{[3
]}

Touret, Franck ^{[3
]}

Coutard, Bruno ^{[3
]}

McBrayer, Tamara R. ^{[4
,5
]}

Schinazi, Raymond F. ^{[4
,5
]}

Agrofoglio, Luigi A. ^{[1
]}

机构：

[1] Univ Orleans, CNRS, Inst Organ & Analyt Chem, UMR 7311, F-45067 Orleans, France

[2] Univ Tours, INSERM, U1259, F-37032 Tours, France

[3] Aix Marseille Univ, Unite Virus Emergents UVE, INSERM 1207, IHU Mediterranee Infect,IRD 190, F-13000 Marseille, France

[4] Emory Univ, Sch Med, Biochem Pharmacol Lab, Ctr AIDS Res,Dept Pediat, Atlanta, GA 30222 USA

[5] Childrens Healthcare Atlanta, Atlanta, GA 30222 USA

来源：

MOLECULES | 2021年 / 26卷 / 05期

关键词：

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

D O I：

10.3390/molecules26051493

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 mu M, without significant cytotoxicity (IC50 = 66.4 mu M in HepG2 cells, IC50 = 43.1 mu M in HepG2 cells) at 10 mu M.

引用

页数：18

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