New dinucleoside phosphonate derivatives as prodrugs of 3'-azido-3'-deoxythymidine and β-L-2',3'-dideoxy-3'-thiacytidine: synthesis and anti-HIV properties.

[Formula: see text]New phosphonate homodimers of 3'-azido-3'-deoxythymidine (AZT) and a phosphonate heterodimer of β-L-2',3'-dideoxy-3'-thiacytidine (3TC) and AZT were synthesized. The compounds demonstrated moderate anti-HIV activity. Stability of the compounds in human blood serum was studied.

Phosphoramidate derivatives of acyclovir: synthesis and antiviral activity in HIV-1 and HSV-1 models in vitro.

The antiviral activity against HIV and HSV and the chemical stability of ACV phosphoramidate derivatives were studied. The phosphoramidates of ACV demonstrated moderate activity. The best compound appeared to be 9-(2-hydroxymethyl)guanine phosphoromonomorpholidate (7), which inhibited virus replication in pseudo-HIV-1 particles by 50% at 50 μM.

[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.

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.

Phosphorodiamides as prodrugs for antiviral nucleosides.

New phosphorodiamides of modified nucleoside monophosphates were synthesized and their antiviral properties 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].

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.

[Ribonucleoside and 2'-deoxyribonucleoside 5'-phosphonates: synthesis and antiviral activity].

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.

[5'-S-nucleoside triphosphates. Synthesis and substrate properties in tests with DNA polymerases].

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.