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 (EC 50 of 1.5 nM and 1.2 nM against genotype 1a and 1b replicons, respectively). A series of piperidine oxazolidinones afforded 27c which showed EC 50's of 10.9 nM and 6.1 nM ...