Pyridine Carboxamides: Potent Palm Site Inhibitors of HCV NS5B Polymerase

Overview

Journal ACS Med Chem Lett

Publisher American Chemical Society

Specialty Chemistry

Date 2014 Jun 6

PMID 24900232

Citations 5

Authors

Cliff C Cheng

Xiaohua Huang

Gerald W Shipps Jr

Yu-Sen Wang

Daniel F Wyss

Kyle A Soucy

Chuan-Kui Jiang

Sony Agrawal

Eric Ferrari

Zhiqing He

H-C Huang

Affiliations

Soon will be listed here.

Abstract

Pyridine carboxamide-based inhibitors of the hepatitis C virus (HCV) NS5B polymerase were diversified and optimized to a variety of topologically related scaffolds. In particular, the 2-methyl nicotinic acid scaffold was developed into inhibitors with improved biochemical (IC50-GT1b = 0.014 μM) and cell-based HCV replicon potency (EC50-GT1b = 0.7 μM). Biophysical and biochemical characterization identified this novel series of compounds as palm site binders to HCV polymerase.

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