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

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

  • ACS Med Chem Lett. 2012 May 24;3(7):565-9. doi: 10.1021/ml300090x.
J Brad Shotwell 1,  Subramanian Baskaran 1,  Pek Chong 1,  Katrina L Creech 2,  Renae M Crosby 1,  Hamilton Dickson 1,  Jing Fang 1,  Dulce Garrido 1,  Amanda Mathis 1,  Jack Maung 1,  Derek J Parks 2,  Jeffrey J Pouliot 1,  Daniel J Price 2,  Roopa Rai 1,  John W Seal 3rd 2,  Uli Schmitz 1,  Vincent W F Tai 1,  Michael Thomson 1,  Mi Xie 1,  Zhiping Z Xiong 1,  Andrew J Peat 1
Affiliations

Affiliations

  • 1 GlaxoSmithKline , Antiviral Discovery Performance Unit, 5 Moore Drive, Research Triangle Park, North Carolina 27709-3398, United States.
  • 2 GlaxoSmithKline , Platform Technology and Science, 5 Moore Drive, Research Triangle Park, North Carolina 27709-3398, United States.
PMID: 24900511 DOI: 10.1021/ml300090x
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.

Keywords

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

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