946511-13-3Relevant academic research and scientific papers
Cyclic phosphoramidates as prodrugs of 2′-C-methylcytidine
Meppen, Malte,Pacini, Barbara,Bazzo, Renzo,Koch, Uwe,Leone, Joseph F.,Koeplinger, Kenneth A.,Rowley, Michael,Altamura, Sergio,Di Marco, Annalise,Fiore, Fabrizio,Giuliano, Claudio,Gonzalez-Paz, Odalys,Laufer, Ralph,Pucci, Vincenzo,Narjes, Frank,Gardelli, Cristina
, p. 3765 - 3770 (2009)
The currently approved treatment for hepatitis C virus infections is a combination of Ribavirin and pegylated Interferon. It leads to a sustained virologic response in approximately only half of the patients treated. For this reason there is an urgent need of new therapeutic agents. 2′-C-Methylcytidine is the first nucleoside inhibitor of the HCV NS5B polymerase that was efficacious in reducing the viral load in patients infected with HCV. The application of a monophosphate prodrug approach based on unprecedented cyclic phosphoramidates is reported. Our SAR studies led to compounds that are efficiently converted to the active triphosphate in human hepatocytes.
Phosphoramidate prodrugs of 2′-C-methylcytidine for therapy of hepatitis C virus infection
Gardelli, Cristina,Attenni, Barbara,Donghi, Monica,Meppen, Malte,Pacini, Barbara,Harper, Steven,Di Marco, Annalise,Fiore, Fabrizio,Giuliano, Claudio,Pucci, Vincenzo,Laufer, Ralph,Gennari, Nadia,Marcucci, Isabella,Leone, Joseph F.,Olsen, David B.,MacCoss, Malcolm,Rowley, Michael,Narjes, Frank
experimental part, p. 5394 - 5407 (2010/04/30)
The application of a phosphoramidate prodrug approach to 2′-C-methylcytidine (NM107), the first nucleoside inhibitor of the hepatitis C virus (HCV) NS5B polymerase, is reported. 2′-C-Methylcytidine, as its valyl ester prodrug (NM283), was efficacious in r
