1. Synthesis and antiviral activity of HCV NS3/4A peptidomimetic boronic acid inhibitors
- Author
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Maria Joshi, Fuxin Qian, Xiaoli Zhang, Xinqiang Li, Marlena Walls, David T. Winn, Amogh Boloor, David Alan Campbell, Ping Wei, Yuliang Zhang, Denise Hanway, Gabriel Mendez, Juan Manuel Betancort, and Michael E. Hepperle
- Subjects
Proteases ,Genotype ,Peptidomimetic ,viruses ,medicine.medical_treatment ,Clinical Biochemistry ,Pharmaceutical Science ,Hepacivirus ,Viral Nonstructural Proteins ,Antiviral Agents ,Biochemistry ,Viral Proteins ,chemistry.chemical_compound ,Cell Line, Tumor ,Drug Discovery ,medicine ,Peptide synthesis ,Humans ,Protease Inhibitors ,Molecular Biology ,chemistry.chemical_classification ,NS3 ,Protease ,biology ,Organic Chemistry ,Intracellular Signaling Peptides and Proteins ,virus diseases ,biochemical phenomena, metabolism, and nutrition ,Boronic Acids ,Hepatitis C ,Enzyme ,chemistry ,Enzyme inhibitor ,biology.protein ,Molecular Medicine ,Mutant Proteins ,Carrier Proteins ,Boronic acid - Abstract
A new series of NS3/4A protease boronic acid inhibitors is described. The compounds show good biochemical potency and cellular activity. The peptidomimetic inhibitors were evaluated against proteases from different HCV genotypes and clinically relevant NS3/4A mutants. Compound 28 displayed subnanomolar to single digit nanomolar potencies in the enzymatic assays and an EC50 of 25 nM in the replicon cell-based assay.
- Published
- 2009