Article
Discovery of Novel Nucleotide Prodrugs with Improved Potency Against HCV Variants Carrying NS5B S282T Mutation.
Journal of medicinal chemistry - 27 Jul 2017
Zhen Le, Dai Liang, Wen Xiaoan, Yao Lan, Jin Xiaoliang, Yang Xiao-Wen, Zhao Wenfeng, Yu Sheng-Qi, Yuan Haoliang, Wang Guangji, Sun Hongbin
Abstract excerpt
Resistant HCV variants carrying NS5B S282T mutation confer reduced sensitivity to sofosbuvir, the sole marketed NS5B polymerase inhibitor. On the basis of the finding that 2'-α-F-2'-β-C-methylcytidine 5'-triphosphate (8) was more potent than sofosbuvir's active metabolite on inhibition of both wild-type and S282T mutant polymerase, a dual-prodrug approach has been established. Twenty-nine phosphoramidates with...
Topics
- Alanine
- Animals
- Antiviral Agents
- Cell Line, Tumor
- Cytidine Monophosphate
- Dogs
- Female
- Hepacivirus
- Humans
- Liver
- Male
- Mutation
- Nucleotides
- Prodrugs