The treatment of HCV with highly efficacious, well-tolerated, interferon-?free regimens has become a compelling clinical goal. Trials employing combinations of direct-?acting antivirals that include NS5A inhibitors have shown significant promise in meeting this challenge. Herein, we describe the exploration of pyrrolidine substitution in a series of bis-benzimidazole NS5A inhibitors and highlight a subtle structural change that profoundly increases genotype 1a potency and can be effectively applied to other series. 

HCV NS5A replication complex inhibitors: Effects of substituted pyrrolidines in balancing genotype 1a/1b potency

248th National Meeting (2014)

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