2. Academic Validation
  3. Discovery of a potent boronic acid derived inhibitor of the HCV RNA-dependent RNA polymerase

Discovery of a potent boronic acid derived inhibitor of the HCV RNA-dependent RNA polymerase

  • J Med Chem. 2014 Mar 13;57(5):1902-13. doi: 10.1021/jm400317w.
Andrew Maynard 1,  Renae M Crosby,  Byron Ellis,  Robert Hamatake,  Zhi Hong,  Brian A Johns,  Kirsten M Kahler,  Cecilia Koble,  Anna Leivers,  Martin R Leivers,  Amanda Mathis,  Andrew J Peat,  Jeffrey J Pouliot,  Christopher D Roberts,  Vicente Samano,  Rachel M Schmidt,  Gary K Smith,  Andrew Spaltenstein,  Eugene L Stewart,  Pia Thommes,  Elizabeth M Turner,  Christian Voitenleitner,  Jill T Walker,  Greg Waitt,  Jason Weatherhead,  Kurt Weaver,  Shawn Williams,  Lois Wright,  Zhiping Z Xiong,  David Haigh,  J Brad Shotwell
Affiliations

Affiliation

  • 1 GlaxoSmithKline, Infectious Diseases Medicines Discovery Unit, 5 Moore Drive, Research Triangle Park, North Carolina 27709-3398, United States.
PMID: 23672667 DOI: 10.1021/jm400317w
Abstract

A boronic acid moiety was found to be a critical pharmacophore for enhanced in vitro potency against wild-type hepatitis C replicons and known clinical polymorphic and resistant HCV mutant replicons. The synthesis, optimization, and structure-activity relationships associated with inhibition of HCV replication in a subgenomic replication system for a series of non-nucleoside boron-containing HCV RNA-dependent RNA polymerase (NS5B) inhibitors are described. A summary of the discovery of 3 (GSK5852), a molecule which entered clinical trials in subjects infected with HCV in 2011, is included.

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