2-(3-Thienyl)-5,6-dihydroxypyrimidine-4-carboxylic acids as inhibitors of HCV NS5B RdRp.
Bioorg Med Chem Lett
; 19(21): 6245-9, 2009 Nov 01.
Article
in En
| MEDLINE
| ID: mdl-19800789
ABSTRACT
A series of 2-(3-thienyl)-5,6-dihydroxypyrimidine-4-carboxylic acid inhibitors of the hepatitis C virus (HCV) NS5B polymerase enzyme are reported. Sulfonyl urea substituted analogs in this series proved to be the most potent active site non-nucleoside inhibitors of NS5B reported to date. These compounds had low nanomolar enzyme inhibition across HCV genotypes 1-3 and showed single digit micromolar inhibition in the HCV replicon assay. This improved cell-based activity allowed the binding mode of these compounds to be probed by selection of resistant mutations against compound 21. The results generated are in broad agreement with the previously proposed binding model for this compound class.
Full text:
1
Database:
MEDLINE
Main subject:
Antiviral Agents
/
RNA-Dependent RNA Polymerase
/
Carboxylic Acids
/
Viral Nonstructural Proteins
/
Hepacivirus
/
Enzyme Inhibitors
Limits:
Humans
Language:
En
Journal:
Bioorg Med Chem Lett
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2009
Type:
Article
Affiliation country:
Italy