Aryl uracil inhibitors of hepatitis C virus NS5B polymerase: Synthesis and characterization of analogs with a fused 5,6-bicyclic ring motif

The synthesis and structure–activity relationships of a novel aryl uracil series which contains a fused 5,6-bicyclic ring unit for HCV NS5B inhibition is described. Several analogs display replicon cell culture potencies in the low nanomolar range along with excellent rat pharmacokinetic values.

Saved in:
Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2013-06, Vol.23 (12), p.3487-3490
Main Authors: Krueger, A. Chris, Randolph, John T., DeGoey, David A., Donner, Pamela L., Flentge, Charles A., Hutchinson, Douglas K., Liu, Dachun, Motter, Christopher E., Rockway, Todd W., Wagner, Rolf, Beno, David W.A., Koev, Gennadiy, Lim, Hock B., Beyer, Jill M., Mondal, Rubina, Liu, Yaya, Kati, Warren M., Longenecker, Kenton L., Molla, Akhteruzzaman, Stewart, Kent D., Maring, Clarence J.
Format: Article
Language:English
Subjects:
Animals
Aryl uracil
Bridged Bicyclo Compounds - chemical synthesis
Bridged Bicyclo Compounds - chemistry
Bridged Bicyclo Compounds - pharmacokinetics
Bridged Bicyclo Compounds - pharmacology
Cell culture
Enzyme Inhibitors - chemical synthesis
Enzyme Inhibitors - chemistry
Enzyme Inhibitors - pharmacokinetics
Enzyme Inhibitors - pharmacology
Hepacivirus - enzymology
Hepatitis C
Hepatitis C virus
NS5B polymerase inhibitors
pharmacokinetics
Rats
replicon
RNA-Dependent RNA Polymerase - antagonists & inhibitors
RNA-Dependent RNA Polymerase - metabolism
Structure-Activity Relationship
structure-activity relationships
uracil
Uracil - antagonists & inhibitors
Uracil - pharmacology
Viral Nonstructural Proteins - antagonists & inhibitors
Viral Nonstructural Proteins - metabolism
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:The synthesis and structure–activity relationships of a novel aryl uracil series which contains a fused 5,6-bicyclic ring unit for HCV NS5B inhibition is described. Several analogs display replicon cell culture potencies in the low nanomolar range along with excellent rat pharmacokinetic values.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2013.04.057