Synthesis of novel substituted N-aryl benzamides as hA3G stabilizers and their inhibitory activities against hepatitis C virus replication

A series of novel amino-substituted N-aryl benzamide analogs were synthesized and evaluated for their ability to inhibit hepatitis C virus (HCV) replication in acutely infected Huh7.5 cells. Most of the substituted N-aryl benzamide compounds showed convincing anti-HCV activities. Compounds 1f, 1g an...

Full description

Saved in:
Bibliographic Details
Published in:Acta pharmaceutica Sinica. B 2013-09, Vol.3 (5), p.312-321
Main Authors: Li, Yanping, Peng, Zonggen, Hao, Lanhu, Wu, Zhouyi, Zhu, Yanping, Hu, Laixing, Jiang, Jiandong, Li, Zhuorong
Format: Article
Language:English
Subjects:
hA3G
HCV inhibitor
N-aryl benzamide
Structure–activity relationship
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:A series of novel amino-substituted N-aryl benzamide analogs were synthesized and evaluated for their ability to inhibit hepatitis C virus (HCV) replication in acutely infected Huh7.5 cells. Most of the substituted N-aryl benzamide compounds showed convincing anti-HCV activities. Compounds 1f, 1g and 4c exhibited potent anti-replicative activity at low micromolar levels (IC50=1.0–2.0 μM) with selective indices (SI) greater than 40. Mechanistic analysis indicated that the active compounds increased intracellular hA3G protein levels and inhibited HCV replication in a dose-dependent manner. The results demonstrate that this series of substituted N-aryl benzamide compounds warrant further investigation as inhibitors of HCV replication.
ISSN:2211-3835
2211-3843
DOI:10.1016/j.apsb.2013.07.002