Synthesis of fluorinated acyclic nucleoside phosphonates with 5-azacytosine base moiety
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F19%3A00509814" target="_blank" >RIV/61388963:_____/19:00509814 - isvavai.cz</a>
Alternative codes found
RIV/68378271:_____/19:00511182
Result on the web
<a href="https://www.sciencedirect.com/science/article/pii/S0040402019308622?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0040402019308622?via%3Dihub</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.tet.2019.130529" target="_blank" >10.1016/j.tet.2019.130529</a>
Alternative languages
Result language
angličtina
Original language name
Synthesis of fluorinated acyclic nucleoside phosphonates with 5-azacytosine base moiety
Original language description
With respect to the strong antiviral activity of (S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]-5-azacytosine various types of its side chain fluorinated analogues were prepared. The title compound, (S)-1-[3-fluoro-2-(phosphonomethoxy)propyl]-5-azacytosine (FPMP-5-azaC) was synthesised by the condensation reaction of (S)-2-[(diisopropoxyphosphoryl)methoxy)-3-fluoropropyl p-toluenesulfonate with a sodium salt of 5-azacytosine followed by separation of appropriate N-1 and O-2 regioisomers and ester hydrolysis. Transformations of FPMP-5-azaC to its 5,6-dihydro-5-azacytosine counterpart, amino acid phosphoramidate prodrugs and systems with an annelated five-membered imidazole ring, i.e. imidazo [1,2-a][1,3,5]triazine derivatives were also carried out. 1-(2-Phosphonomethoxy-3,3,3-trifluoropropyl)-5-azacytosine was prepared from 5-azacytosine and trifluoromethyloxirane to form 1-(3,3,3-trifluoro-2-hydroxypropyl)-5-azacytosine which was treated with diisopropyl bromomethane-phosphonate followed by deprotection of esters. Antiviral activity of all newly prepared compounds was studied. FPMP-5-azaC diisopropyl ester inhibited the replication of herpes viruses with EC50 values that were about three times higher than that of the reference anti-HCMV drug ganciclovir without displaying cytotoxicity.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10401 - Organic chemistry
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Tetrahedron
ISSN
0040-4020
e-ISSN
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Volume of the periodical
75
Issue of the periodical within the volume
39
Country of publishing house
GB - UNITED KINGDOM
Number of pages
13
Pages from-to
130529
UT code for WoS article
000488140900002
EID of the result in the Scopus database
2-s2.0-85071143063