Synthesis and antiviral activities of hexadecyloxypropyl prodrugs of acyclic nucleoside phosphonates containing guanine or hypoxanthine and a (S)-HPMP or PEE acyclic moiety
Language English Country France Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
22858222
PubMed Central
PMC7115494
DOI
10.1016/j.ejmech.2012.07.027
PII: S0223-5234(12)00453-9
Knihovny.cz E-resources
- MeSH
- Antiviral Agents chemical synthesis chemistry metabolism pharmacology MeSH
- Cell Line MeSH
- DNA Viruses drug effects MeSH
- Guanine analogs & derivatives chemistry MeSH
- Hypoxanthine chemistry MeSH
- Hypoxanthines chemistry MeSH
- Phosphorous Acids chemistry MeSH
- Humans MeSH
- Nucleosides chemistry MeSH
- Organophosphonates chemical synthesis chemistry metabolism pharmacology MeSH
- Prodrugs metabolism MeSH
- Chemistry Techniques, Synthetic MeSH
- Structure-Activity Relationship MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Antiviral Agents MeSH
- Guanine MeSH
- Hypoxanthine MeSH
- Hypoxanthines MeSH
- Phosphorous Acids MeSH
- Nucleosides MeSH
- Organophosphonates MeSH
- Prodrugs MeSH
Hexadecyloxypropyl esters of acyclic nucleoside phosphonates containing guanine (G) or hypoxanthine (Hx) and a (S)-[3-hydroxy-2-(phosphonomethoxy)propyl] [(S)-HPMP] or 2-(2-phosphonoethoxy)ethyl (PEE) acyclic moiety have been prepared. The activity of the prodrugs was evaluated in vitro against different virus families. Whereas ester derivatives of PEEHx and (S)-HPMPHx were antivirally inactive, monoesters of PEEG, and mono- and diesters of (S)-HPMPG showed pronounced antiviral activity against vaccinia virus and/or herpesviruses. Monoesters of (S)-HPMPG emerged as the most potent and selective derivatives against these DNA viruses. None of the compounds were inhibitory against RNA viruses and retroviruses.
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