1. Discovery of pentacyclic compounds as potent inhibitors of hepatitis C virus NS5B RNA polymerase
- Author
-
Uwe Koch, Frank Narjes, Elena Capito, Joerg Habermann, and Maria del Rosario Rico Ferreira
- Subjects
Models, Molecular ,Tertiary amine ,viruses ,Hepatitis C virus ,Chemistry, Pharmaceutical ,Clinical Biochemistry ,Molecular Conformation ,Pharmaceutical Science ,Viral Nonstructural Proteins ,medicine.disease_cause ,Biochemistry ,Virus ,chemistry.chemical_compound ,Inhibitory Concentration 50 ,Structure-Activity Relationship ,RNA polymerase ,Drug Discovery ,medicine ,Humans ,Replicon ,Enzyme Inhibitors ,Molecular Biology ,NS5B ,chemistry.chemical_classification ,biology ,Organic Chemistry ,DNA-Directed RNA Polymerases ,Benzazepines ,Enzyme ,chemistry ,Liver ,Models, Chemical ,Enzyme inhibitor ,Drug Design ,biology.protein ,Molecular Medicine ,RNA, Viral - Abstract
We report a new series of inhibitors for hepatitis C virus NS5B RNA polymerase containing a constrained pentacyclic scaffold. Our SAR studies led to the identification of hexahydroindolo[2,1-a]pyrrolo[3,2-d][2]benzazepines exposing basic groups. The compounds displayed a high activity in the enzyme assay and displayed good activity in the cell-based (replicon) assay in the presence of serum proteins.
- Published
- 2008