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Acyclic nucleoside and nucleotide analogues are of great interest. Since Nobel-winning Acyclovir, the most used acyclic nucleoside against herpes viruses, appeared, many successful attempts and achievements in this scope has been made [1]. Phosphonate moiety is a useful bypass of the limiting first phosphorylation step and does not undergo enzymatic hydrolysis as natural phosphates do. Several acyclic nucleoside phosphonate-based drugs are currently in clinical use for treatment of viral infections (e.g. Tenofovir, Cidofovir, Adefovir). The flexible acyclic chain possesses higher range of conformations giving an opportunity to bind more nucleotide-involved enzymes – thus, a combined activity against more viruses can be expected. It is quite essential since over 80% of HIV-infected patients suffer from herpes and other virus-induced infections. In our recent study we have synthesized new acyclic nucleotide analogues with broad antiviral activity. One of the series is oxime-containing nucleoside phosphonates: 9-{2-[(phosphonomethyl)oximino]ethyl}adenine, -guanine and 9-{2-[(phosphonomethyl)oximino]propyl}adenine. Oximes are rarely used in drug design and yet their conformational rigidness and their stability in hydrolytic tests may be useful for nucleoside side chain drug design [2]. The compounds were synthesized using modified Mitsunobu procedure for key intermediate diethyl aminooxymethylphosphonate, which allowed to double the yield of the original synthesis [3]. The efficient oxime forming “click” reaction was performed to form the target structures. A convenient procedure for aminooxy group detection was proposed. Products displayed moderate activity against HIV and herpes viruses in cell cultures and hepatitis virus C in replicon system without any toxicity up to 1000 μM. Other series of the compounds will be further discussed.