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Imidazo[1,2-a]pyridines That Directly Interact with Hepatitis C NS4B: Initial Preclinical Characterization
J Brad Shotwell1, Subramanian Baskaran1, Pek Chong1
1GlaxoSmithKline , Antiviral Discovery Performance Unit, 5 Moore Drive, Research Triangle Park, North Carolina 27709-3398, United States.
Abstract:
A series of imidazo[1,2-a]pyridines which directly bind to HCV Non-Structural Protein 4B (NS4B) is described. This series demonstrates potent in vitro 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.
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