[Non-hydrolysable analogs of inorganic pyrophosphate as inhibitors of hepatitis C virus RNA-dependent RNA-polymerase].

Inorganic pyrophosphate (PPi) is a product of the polymerization reaction catalyzed by DNA- and RNA-polymerases. We have synthesized a number of novel non-hydrolysable PPi analogues, some of them have demonstrated inhibition of polymerization reaction catalyzed by hepatitis C virus RNA-dependent RNA-polymerase (NS5B). A new pharmacophore has been developed based on non-hydrolysable methylene-diphosphonate backbone.

[The study of coupling agents for the phosphorylation of 3'-azido-3'-deoxythymidine with (P32)orthophosphoric acid].

The kinetics of 3'-azido-3'-deoxythymidine phosphorylation with [32P]orthophosphoric acid was studied in the presence of various coupling agents. The most effective method with the use of BrCN provided the isolation of the target 3'-azido-3'-deoxythymidine 5'-[32P]monophosphate in 46% yield and a high specific radioactivity (>100 Ci/mmol).

[New phosphonoformic acid derivatives of 3'-azido-3'-deoxythymidine].

New 5'-alkyl ethoxy- and aminocarbonylphosphonates of 3'-azido-3'-deoxythymidine (AZT) were synthesized, and their antiviral properties in HIV-1-infected cell cultures and stability to chemical hydrolysis were studied. The AZT 5'-aminocarbonylphosphonates were shown to be significantly more stable in phosphate buffer (pH 7.2) than the corresponding ethoxycarbonylphosphonates.