Abstract
The synthesis and optimisation of HCV NS5B polymerase inhibitors with improved potency versus the existing compound 1 is described. Substitution in the benzothiadiazine portion of the molecule, furnishing improvement in potency in the high protein Replicon assay, is highlighted, culminating in the discovery of 12h, a highly potent oxyacetamide derivative.
MeSH terms
-
Administration, Oral
-
Animals
-
Antiviral Agents / chemical synthesis*
-
Antiviral Agents / pharmacology
-
Benzothiadiazines / chemistry*
-
Benzothiadiazines / pharmacology
-
Chemistry, Pharmaceutical / methods*
-
Drug Design
-
Hepacivirus / enzymology*
-
Humans
-
Inhibitory Concentration 50
-
Models, Chemical
-
Molecular Conformation
-
Molecular Structure
-
Rats
-
Structure-Activity Relationship
-
Viral Nonstructural Proteins / antagonists & inhibitors*
Substances
-
Antiviral Agents
-
Benzothiadiazines
-
Viral Nonstructural Proteins
-
NS-5 protein, hepatitis C virus