Non-hydrolysable analogues of inorganic pyrophosphate as inhibitors of hepatitis C virus RNA-dependent RNA-polymerase

Article abstract of DOI:10.1134/S1068162012020124

Inorganic pyrophosphate (PP_i) is the product of the polymerization reaction catalyzed by DNA-and RNA-polymerases. A number of novel non-hydrolsable PP_i analogues was synthesized; some of them inhibited the polymerization reaction catalyzed by hepatitis C virus RNA-dependent RNA-polymerase (NS5B). A new pharmacophore based on a non-hydrolysable methylenediphosphonate backbone has been developed. The structure-activity relationship analysis of 12 bisphosphonates is presented and the structural features crucial for NS5B polymerase activity inhibition are stated. Pleiades Publishing, Ltd., 2012.