1350735-57-7Relevant articles and documents
Discovery of the first C -nucleoside HCV polymerase inhibitor (GS-6620) with demonstrated antiviral response in HCV infected patients
Cho, Aesop,Zhang, Lijun,Xu, Jie,Lee, Rick,Butler, Thomas,Metobo, Sammy,Aktoudianakis, Vangelis,Lew, Willard,Ye, Hong,Clarke, Michael,Doerffler, Edward,Byun, Daniel,Wang, Ting,Babusis, Darius,Carey, Anne C.,German, Polina,Sauer, Dorothea,Zhong, Weidong,Rossi, Stephen,Fenaux, Martijn,McHutchison, John G.,Perry, Jason,Feng, Joy,Ray, Adrian S.,Kim, Choung U.
, p. 1812 - 1825 (2014/04/03)
Hepatitis C virus (HCV) infection presents an unmet medical need requiring more effective treatment options. Nucleoside inhibitors (NI) of HCV polymerase (NS5B) have demonstrated pan-genotypic activity and durable antiviral response in the clinic, and they are likely to become a key component of future treatment regimens. NI candidates that have entered clinical development thus far have all been N-nucleoside derivatives. Herein, we report the discovery of a C-nucleoside class of NS5B inhibitors. Exploration of adenosine analogs in this class identified 1′-cyano-2′-C-methyl 4-aza-7,9-dideaza adenosine as a potent and selective inhibitor of NS5B. A monophosphate prodrug approach afforded a series of compounds showing submicromolar activity in HCV replicon assays. Further pharmacokinetic optimization for sufficient oral absorption and liver triphosphate loading led to identification of a clinical development candidate GS-6620. In a phase I clinical study, the potential for potent activity was demonstrated but with high intra- and interpatient pharmacokinetic and pharmacodynamic variability.
METHODS FOR TREATING HCV
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, (2013/03/28)
This invention relates to combinations of therapeutic molecules useful for treating hepatitis C virus infection. The present invention relates to methods, uses, dosing regimens, and compositions.