Kinase bypass approach for the treatment of Hepatitis C virus infection

By Narjes, Frank; Donghi, Monica; Meppen, Malte; Attenni, Barbara; Pacini, Barbara; Olsen, David B.; Carroll, Steve S.; MacCoss, Malcolm; Leone, Joseph F.; Di Marco, Annalise; et al
From Abstracts of Papers, 239th ACS National Meeting, San Francisco, CA, United States, March 21-25, 2010 (2010), MEDI-347. Language: English, Database: CAPLUS

Infections caused by Hepatitis C Virus (HCV) are a significant world health problem for which novel therapies are in urgent demand. The NS5B RNA dependent RNA polymerase of HCV is responsible for the replication of viral RNA and has been a prime target in the search for novel HCV therapeutics. The application of a kinase bypass approach to the nucleoside inhibitor 2′-C-Methylcytidine will be presented. SAR around the 5′-phosphoramidate class of prodrugs 1 led to the identification of novel classes of compds., which formed efficiently nucleotide triphosphate 2 in HCV subgenomic replicon cells and in hepatocytes of different species. The in vivo profile of selected compds. in preclin. species will be presented.