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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

Authors :
Andrew Maynard
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
Source :
Journal of Medicinal Chemistry. 57:1902-1913
Publication Year :
2013
Publisher :
American Chemical Society (ACS), 2013.

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.

Details

ISSN :
15204804 and 00222623
Volume :
57
Database :
OpenAIRE
Journal :
Journal of Medicinal Chemistry
Accession number :
edsair.doi.dedup.....e6ce7599d644e69b47104c8ac1a7db2e
Full Text :
https://doi.org/10.1021/jm400317w