Literature DB >> 24900511

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

J Brad Shotwell1, Subramanian Baskaran1, Pek Chong1, Katrina L Creech2, Renae M Crosby1, Hamilton Dickson1, Jing Fang1, Dulce Garrido1, Amanda Mathis1, Jack Maung1, Derek J Parks2, Jeffrey J Pouliot1, Daniel J Price2, Roopa Rai1, John W Seal2, Uli Schmitz1, Vincent W F Tai1, Michael Thomson1, Mi Xie1, Zhiping Z Xiong1, Andrew J Peat1.   

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.

Entities:  

Keywords:  NS4B; hepatitis C virus; imidazo[1,2-a]pyridines; replicon

Year:  2012        PMID： 24900511      PMCID： PMC4025644          DOI： 10.1021/ml300090x

Source DB:  PubMed          Journal:  ACS Med Chem Lett        ISSN： 1948-5875            Impact factor:   4.345


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