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发现 3'-氟-5'-去氮胞苷膦酸酯的 L-构型作为有效的抗 HIV 药物。

Discovery of an L-like Configuration for 3'-Fluoro-5'-norcarbonucleoside Phosphonates as Potent Anti-HIV Agents.

机构信息

Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, Université de Montpellier, CNRS, ENSCM, 1019, route de Mende, 34293, Montpellier, France.

出版信息

ChemMedChem. 2022 Oct 19;17(20):e202200377. doi: 10.1002/cmdc.202200377. Epub 2022 Sep 15.

DOI:10.1002/cmdc.202200377
PMID:36032023
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9825896/
Abstract

Recently, we reported the racemic synthesis of 3'-fluoro-5'-norcarbocyclic nucleoside phosphonates bearing adenine as the heterocyclic base. For this study, to evaluate the antiviral activity of each enantiomer, we synthesized both enantiomers, as well as their corresponding bis(POM) prodrugs. Anti-HIV-1 evaluation against the LAI strain and clinically NRTI-resistant HIV-1 strains are presented. The activities against these different strains show that the activities of bis(POM) prodrug (-)-9 are equivalent or even superior to those of (R)-PMPA.

摘要

最近，我们报道了含有腺嘌呤作为杂环碱基的 3'-氟-5'-去氮环胞苷膦酸酯的外消旋合成。在这项研究中，为了评估每个对映异构体的抗病毒活性，我们合成了两种对映异构体及其相应的双(POM)前药。本文对抗 HIV-1 的 LAI 株和临床 NRTI 耐药 HIV-1 株的活性进行了评估。对这些不同菌株的活性表明，双(POM)前药(-)-9 的活性与(R)-PMPA 相当甚至更优。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ce0/9825896/bf9d44926210/CMDC-17-0-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ce0/9825896/cab205b421fd/CMDC-17-0-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ce0/9825896/7cc431f84cac/CMDC-17-0-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ce0/9825896/05795bb5a346/CMDC-17-0-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ce0/9825896/062d451e2fea/CMDC-17-0-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ce0/9825896/bf9d44926210/CMDC-17-0-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ce0/9825896/cab205b421fd/CMDC-17-0-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ce0/9825896/7cc431f84cac/CMDC-17-0-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ce0/9825896/05795bb5a346/CMDC-17-0-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ce0/9825896/062d451e2fea/CMDC-17-0-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ce0/9825896/bf9d44926210/CMDC-17-0-g002.jpg

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