Related Experiment Video
Updated: May 1, 2026

A Protocol for Analyzing Hepatitis C Virus Replication
Published on: June 26, 2014
Design and synthesis of spirocyclic compounds as HCV replication inhibitors by targeting viral NS4B protein
Vincent W-F Tai1, Dulce Garrido1, Daniel J Price2
1GlaxoSmithKline, Antiviral Discovery Performance Unit, 5 Moore Drive, Research Triangle Park, NC 27709, USA.
Abstract:
Two novel series of spirocyclic piperidine analogs appended to a pyrazolo[1,5-a]pyridine core were designed, synthesized and evaluated for their anti-HCV activity. A series of piperidine ketals afforded dispiro 6p which showed excellent in vitro anti-HCV activities (EC50 of 1.5nM and 1.2nM against genotype 1a and 1b replicons, respectively). A series of piperidine oxazolidinones afforded 27c which showed EC50's of 10.9nM and 6.1nM against 1a and 1b replicons, respectively. Both compounds 6p and 27c bound directly to non-structural NS4B protein in vitro (IC50's=10.2 and 30.4nM, respectively) and exhibited reduced potency in replicons containing resistance mutations encoding changes in the NS4B protein.
More Related Videos
Related Concept Videos
Inhibitors of Viral Protein Synthesis
Retrovirus Life Cycles
Viruses with RNA Genomes
Inhibitors of Bacterial DNA Synthesis
Inhibitors of Bacterial Protein Synthesis
Hepatitis

