Imidazo[1,2-<i>a</i>]pyridines That Directly Interact with Hepatitis C NS4B: Initial Preclinical Characterization

Abstract

A series of imidazo­[1,2-<i>a</i>]­pyridines which directly bind to HCV Non-Structural Protein 4B (NS4B) is described. This series demonstrates potent <i>in vitro</i> inhibition of HCV replication (EC₅₀ < 10 nM), direct binding to purified NS4B protein (IC₅₀ < 20 nM), and an HCV resistance pattern associated with NS4B (H94N/R, V105L/M, F98L) that are unique among reported HCV clinical assets, suggestive of the potential for additive or synergistic combination with other small molecule inhibitors of HCV replication