[Phosphoramidate derivatives of acyclovir--herpes virus replication inhibitors].

A number of new phosphoramidates of acyclovir--compounds of interest as anti-virals against resistant strains of virus herpes was synthesized. Several methods of synthesis of these compounds were suggested. Optimal method appeared to be the obtaining of phosphoramidates through the phosphomonocloride with its subsequent treatment with various amines. Two compounds have shown moderate activity against HSV-1.

Base-modified ribonucleosides as potential anti-hepatitis C virus agents.

Four novel series of base modified ribonucleoside analogues were synthesized and evaluated as potential anti-HCV agents. For two compounds notable anti-HCV activity was observed The triphosphates of bicyclic pyrimidine ribonucleosides were studied as substrates/inhibitors of HCV RNA-dependent RNA polymerase (RdRp, NS5B protein) and RNA helicase/NTPase (NS3 protein).

[The synthesis of N2,N6-substituted diaminopurine ribosides].

A series of new 2,6-substituted diaminopurine riboside derivatives were synthesized by activation of protected xantosine with sulfonyl chlorides followed by treatment with various amines. The relationship between the reactivity of intermediates and the nature of the activating agents was studied.

A new approach to the synthesis of optically active alkylated adenine derivatives.

A new synthesis of chiral acyclic nucleoside and nucleotide analogues starting from d(-)- or l(+)-riboses was proposed. Antiviral properties of the synthesized compounds towards the pox virus family were evaluated.

Synthesis of [bis(inosine-5')]-tetraphosphate and [bis(inosine-5')]-pentaphosphate analogues bearing the residues of methylenediphosphonic acid.

Various methods of synthesis of metabolically stable phosphonate analogues of bisnucleoside oligophosphates containing two residues of methylenediphosphonic acid in the oligophosphate chain are studied. Phosphonate analogues of Ip4I and Ip5I are prepared.

[Study of reverse transcriptase selectivity. Substrate properties of new 2',3'-unsaturated acyclic nucleotide analogs]. / Izuchenie selektivnosti obratnykh transkriptaz. Substratnye svoistva novykh 2',3'-nenasyshchennykh atsiklicheskikh nukleotidnykh analogov.

A new series of nucleotide analogs, (Z)-pyrophosphoryl (phosphonyloxymethyl) but-2-enyl derivatives of pyrimidines and purines, was synthesized. Their substrate and inhibitory properties toward some DNA polymerases and reverse transcriptases were evaluated. They were shown to be selective inhibitors of HIV reverse transcriptase. The structure-substrate properties relationships for nucleotide analogs were discussed.

[Ribonucleoside and 2'-deoxyribonucleoside 5'-phosphonates: synthesis and antiviral activity]. / 5'-Fosfonaty ribonukleozidov i 2'-dezoksiribonukleozidov: sintez i antivirusnaia aktivnost'.

Groups of 5'-phosphonates of natural 2'-deoxynucleosides and ribonucleosides were synthesized by condensation of 3'-acetylated 2'-deoxynucleosides or 2',3'-substituted (2',3'-O-isopropylidene, 2',3'-O-methoxymethylene, or 2',3'-O-ethoxymethylene) ribonucleosides. As condensing agents, either N,N'-dicyclohexylcarbodiimide or 2,4,6-triisopropylbenzenesulphonyl chloride were used. Nucleoside 5'-ethoxycarbonyl-phosphonates were converted into corresponding nucleoside 5'-aminocarbonylphosphonates by the action of ammonia in methanol. All compounds were tested for inhibition of several viruses, including human herpes simplex virus type 2 and cytomegalovirus, but showed no activity. A few compounds insignificantly inhibited human immunodeficiency virus type 1 reproduction. Thymidine 5'-hydrogenphosphonate neutralized the anti HIV action of 3'-azido-3'-deoxythymidine, thus indirectly showing that it could be partly hydrolyzed in cell culture to corresponding thymidine.

[5'-S-nucleoside triphosphates. Synthesis and substrate properties in tests with DNA polymerases]. / 5'-S-nukleozidtrifosfaty. Sintez i substratnye svoistva v testakh s DNA-polimerazami.

In the course of our investigations on DNA polymerases a synthesis of new triphosphate analogues, 5'-mercapto-5'-deoxythymidine 5'-S-triphosphate and 5'-mercapto-3',5'-dideoxythymidine 5'-S-triphosphate, was brought about starting from 3'-O-acetyl-thymidine and 3'-deoxythymidine, respectively. The former compound proved to be a weak substrate for E. coli DNA polymerase I and AMV reverse transcriptase and inactive towards DNA polymerases alpha from placenta and beta from rat liver. The second synthesized triphosphate was incorporated into DNA chain by none of the tested enzymes. Probable reasons for so strong a decrease in the substrate properties of the prepared compounds are discussed.