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New amphiphilic prodrugs of adefovir and cidofovir
Tichý, Tomáš ; Andrei, G. ; Dračínský, Martin ; Holý, Antonín ; Balzarini, J. ; Snoeck, R. ; Krečmerová, Marcela
New adefovir (PMEA) prodrugs with a pro-moiety consisting of decyl(oxyethyl) chain bearing hydroxyl function(s), hexaethyleneglycol or a (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl unit were prepared from the tetrabutylammonium salt of the phosphonate drug and an appropriate alkyl bromide or tosylate. Analogously, two esters of Cidofovir [(S)-HPMPC] bearing a hexaethyleneglycol moiety were prepared. The antiviral activity of the prodrugs was evaluated in vitro. A loss in the antiviral activities of the hydroxylated decyl(oxyethyl) esters and hexaethyleneglycol esters of PMEA against HIV and herpesviruses. (S)-HPMPC prodrugs exhibited anticytomegalovirus activities in the same range as the parent drug, whereas the anti-HSV and anti-VZV activities were one- to seven-fold lower than that of Cidofovir.
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Acyclic Nucleoside Phosphonates as Inhibitors of Hypoxanthine-Guanine-Xanthine Phosphoribosyltransferase: New Anti-Malarial Chemotherapy Leads
Hocková, Dana ; Holý, Antonín ; Česnek, Michal ; Baszczyňski, Ondřej ; Tichý, Tomáš ; Krečmerová, Marcela ; Janeba, Zlatko ; Skinner-Adams, T. S. ; Naesens, L. ; Keough, D. T. ; de Jersey, J. ; Guddat, L. W.
Hypoxanthine-guanine-xanthine phosphoribosyltransferase (HGXPRTase) is a widely recognized target for the discovery of new anti-malarial drugs. Specific acyclic nucleoside phosphonates (ANPs) inhibit HGXPRTase and possess anti-plasmodial activity. Within the framework of a SAR-study, the classical ANPs (e.g. PME-, PMP- and HPMP-derivatives) as well as novel series of compounds were tested to investigate their efficiency and selectivity on the inhibition of P. falciparum, P. vivax and human enzyme.
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The optimized microwave-assisted decomposition of formamides and its synthetic utility in the amination of purines and pyrimidines
Čechová, Lucie ; Jansa, Petr ; Šála, Michal ; Dračínský, Martin ; Holý, Antonín ; Janeba, Zlatko
The microwave-assisted decomposition of DMF was thoroughly studied and the reaction conditions (temperature, solvent effect, and effect of additives such as acids, bases, and salts) were optimized for its use in the amination reactions of various purines and pyrimidines.
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