37635-25-9Relevant academic research and scientific papers
Methylene bisphosphonates as the inhibitors of HIV RT phosphorolytic activity
Yanvarev,Korovina,Usanov,Khomich,Veps?l?inen,Puljula,Kukhanova,Kochetkov
, p. 153 - 162 (2016/06/13)
The structure-function analysis of 36 methylenebisphosphonates (BPs) as inhibitors of the phosphorolytic activity of native and drug-resistant forms of HIV-1 reverse transcriptase (RT) was performed. It was shown that with the increase of the inhibitory potential of BPs towards the phosphorolytic activity raises their ability to inhibit the RT-catalyzed DNA elongation. Herein, we report the impact of the thymidine analog mutations (TAM) on the activity of bisphosphonates, as well as some structural features of the BPs, allowing them to maintain the inhibitory activity on the enzyme resistant to nucleoside analog therapy. We estimated the Mg2+-coordinating group structure, the linker and the aromatic pharmacophore influence on the inhibitory potential of the BPs. Based on the 31 BPs SAR, several BPs with improved inhibitory properties were designed and synthesized.
Non-hydrolysable analogues of inorganic pyrophosphate as inhibitors of hepatitis C virus RNA-dependent RNA-polymerase
Yanvarev,Korovina,Usanov,Kochetkov
experimental part, p. 224 - 229 (2012/08/27)
Inorganic pyrophosphate (PPi) is the product of the polymerization reaction catalyzed by DNA-and RNA-polymerases. A number of novel non-hydrolsable PPi 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.
