Pyridine Carboxamides: Potent Palm Site Inhibitors of HCV NS5B Polymerase

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...

Full description

Saved in:

Bibliographic Details
Published in:	ACS medicinal chemistry letters Vol. 1; no. 9; pp. 466 - 471
Main Authors:	Cheng, Cliff C, Huang, Xiaohua, Shipps, Gerald W, Wang, Yu-Sen, Wyss, Daniel F, Soucy, Kyle A, Jiang, Chuan-kui, Agrawal, Sony, Ferrari, Eric, He, Zhiqing, Huang, H.-C
Format:	Journal Article
Language:	English
Published:	United States American Chemical Society 09-12-2010
Subjects:	Letter palm site inhibitors HCV NS5B polymerase direct-acting antiviral (DAA) 2D 15N-HSQC Hepatitis C virus automated ligand identification system (ALIS)
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1948-5875 1948-5875
DOI:	10.1021/ml100128h