New prodrugs of two pyrimidine acyclic nucleoside phosphonates: Synthesis and antiviral activity

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F17%3A00477657" target="_blank" >RIV/61388963:_____/17:00477657 - isvavai.cz</a>
Result on the web
<a href="http://dx.doi.org/10.1016/j.bmc.2017.06.046" target="_blank" >http://dx.doi.org/10.1016/j.bmc.2017.06.046</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.bmc.2017.06.046" target="_blank" >10.1016/j.bmc.2017.06.046</a>

Result language
angličtina
Original language name
New prodrugs of two pyrimidine acyclic nucleoside phosphonates: Synthesis and antiviral activity
Original language description
New 2,4-diamino-6-[2-(phosphonomethoxy) ethoxy] pyrimidine (PMEO-DAPy) and 1-[2-(phosphonomethoxy) ethyl]-5-azacytosine (PME-5-azaC) prodrugs were prepared with a pro-moiety consisting of carbonyloxymethyl esters (POM, POC), alkoxyalkyl esters, amino acid phosphoramidates and/or tyrosine. The activity of the prodrugs was evaluated in vitro against different virus families. None of the synthesized prodrugs demonstrated activity against RNA viruses but some of them proved active against herpesviruses [including herpes simplex virus (HSV), varicella-zoster virus (VZV), and human cytomegalovirus (HCMV)]. The bis(POC) and the bis(amino acid) phosphoramidate prodrugs of PMEO-DAPy inhibited herpesvirus replication at lower doses than the parent compound although the selectivity against HSV and VZV was only slightly improved compared to PMEO-DAPy. The mono-octadecyl ester of PME5- azaC emerged as the most potent and selective PME-5-azaC prodrug against HSV, VZV and HCMV with EC50's of 0.15-1.12 mM while PME-5-azaC only had marginal anti-herpesvirus activity. Although the bis (hexadecylamido-L-tyrosyl) and the bis(POM) esters of PME-5-azaC were also very potent anti-herpesvirus drugs, these were less selective than the mono-octadecyl ester prodrug.
Czech name
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Czech description
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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

Project
<a href="/en/project/GA14-00522S" target="_blank" >GA14-00522S: Syntheses of new prodrug forms of biologically active nucleotide analogues</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year
2017
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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