Bitte benutzen Sie diese Kennung, um auf die Ressource zu verweisen:
http://dx.doi.org/10.18419/opus-13535
Autor(en): | Han, Jianyang Arnold, Jakob Pannecouque, Christophe Andrei, Graciela Snoeck, Robert Richert, Clemens |
Titel: | Derivatives of 3′‐azidothymidine with 6‐cyanopyridone as base or as phosphoramidate ester and their antiretroviral activity |
Erscheinungsdatum: | 2022 |
Dokumentart: | Zeitschriftenartikel |
Seiten: | 13 |
Erschienen in: | Helvetica chimica acta 106 (2023), No. e202200157 |
URI: | http://nbn-resolving.de/urn:nbn:de:bsz:93-opus-ds-135540 http://elib.uni-stuttgart.de/handle/11682/13554 http://dx.doi.org/10.18419/opus-13535 |
ISSN: | 1522-2675 0018-019X |
Zusammenfassung: | Strongly pairing ethynylpyridone C‐nucleosides are attractive surrogates for thymidine in oligonucleotides. Exploratory work on the antiviral activity of 3′‐azidothymidine (AZT) derivatives with ethynylpyridone as base had identified strong lipophilicity as a limiting factor. Two strategies are being pursued to overcome this issue. In order to make the base more polar, the ethynyl group has been replaced with a cyano group, leading to a cyanopyridone C‐nucleoside, whose eleven‐step synthesis is reported here, together with the synthesis of a 3′‐azido‐2′,3′‐dideoxynucleoside derivative. The base pairing with adenine in a DNA duplex was studied by UV melting analysis of a self‐complementary hexamer containing the 6‐cyano‐2′‐deoxynucleoside instead of thymidine. A melting point increase of 2 °C compared to the unmodified control was found. The other strategy employs a phosphoramidate prodrug design with less lipophilic amino acid esters. Here, anti‐HIV test of the alaninyl and prolinyl methyl esters of AZT gave promising results in cell culture experiments, increasing the selectivity index up to 5.8‐fold for the IIIB strain and up to 5‐fold for the ROD strain of the virus, as compared to the parent nucleoside. These findings help to design the next generation of pyridone C‐nucleosides with potential applications as antivirals. |
Enthalten in den Sammlungen: | 03 Fakultät Chemie |
Dateien zu dieser Ressource:
Datei | Beschreibung | Größe | Format | |
---|---|---|---|---|
HLCA_HLCA202200157.pdf | 7,89 MB | Adobe PDF | Öffnen/Anzeigen |
Diese Ressource wurde unter folgender Copyright-Bestimmung veröffentlicht: Lizenz von Creative Commons