Acyclic nucleoside phosphonates with 5-azacytosine base moiety substituted in C-6 position
Language English Country Great Britain, England Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
19914075
DOI
10.1016/j.bmc.2009.10.044
PII: S0968-0896(09)00979-1
Knihovny.cz E-resources
- MeSH
- Antiviral Agents chemistry pharmacology MeSH
- Cell Line MeSH
- Chlorocebus aethiops MeSH
- Cytosine analogs & derivatives chemistry pharmacology MeSH
- Humans MeSH
- Nucleosides chemistry pharmacology MeSH
- Organophosphonates chemistry pharmacology MeSH
- Vero Cells MeSH
- Virus Diseases drug therapy MeSH
- Viruses drug effects 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
- 5-azacytosine MeSH Browser
- Antiviral Agents MeSH
- Cytosine MeSH
- Nucleosides MeSH
- Organophosphonates MeSH
Two methods for preparation of 6-substituted derivatives of anti DNA-viral agent 1-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]-5-azacytosine (HPMP-5-azaC) were developed: (1) ammonia mediated ring-opening reaction of diisopropyl esters of HPMP-5-azaC (4) to carbamoylguanidine derivatives followed by ring-closure reaction with orthoesters and (2) condensation reaction of 6-substituted 5-azacytosines with diisopropyl (1S)-[2-hydroxy-1-tosyloxymethyl)ethoxy]methylphosphonate (15). Deprotection of diisopropyl esters to free phosphonic acids was performed with bromotrimethylsilane in acetonitrile followed by hydrolysis. In contrast to parent compound HPMP-5-azaC, a substantial decrease of antiviral activity in case of 6-substituted analogues occurred. Surprisingly, N-3 isomer of 6-methyl-HPMP-5-azaC in the form of isopropyl ester revealed activity against RNA viruses (Sindbis virus).
References provided by Crossref.org
Synthesis of fluorinated acyclic nucleoside phosphonates with 5-azacytosine base moiety
