The discovery and structure–activity relationships of pyrano[3,4- b]indole based inhibitors of hepatitis C virus NS5B polymerase

• Published in: Bioorganic & medicinal chemistry letters 2010-05, Vol.20 (9), p.2968-2973
• Main Authors: LaPorte, Matthew G., Draper, Tandy L., Miller, Lori E., Blackledge, Charles W., Leister, Lara K., Amparo, Eugene, Hussey, Alison R., Young, Dorothy C., Chunduru, Srinivas K., Benetatos, Christopher A., Rhodes, Gerry, Gopalsamy, Ariamala, Herbertz, Torsten, Burns, Christopher J., Condon, Stephen M.
• Format: Article
• Language: English
• Subjects: Allosteric properties; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Antiviral Agents - chemical synthesis; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; Binding Sites; Biological and medical sciences; Crystallography, X-Ray; Drug Discovery; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; HCV NS5B polymerase; Hepatitis C virus; Indoles - chemical synthesis; Indoles - chemistry; Indoles - pharmacology; Medical sciences; Pharmacology. Drug treatments; Pyranoindoles; Pyrans - chemical synthesis; Pyrans - chemistry; Pyrans - pharmacology; Structure-Activity Relationship; Viral Nonstructural Proteins - antagonists & inhibitors; Viral Nonstructural Proteins - metabolism
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2010.03.002

We describe the structure–activity relationship of the C1-group of pyrano[3,4- b]indole based inhibitors of HCV NS5B polymerase. Further exploration of the allosteric binding site led to the discovery of the significantly more potent compound 12. We describe the structure–activity relationship of the C1-group of pyrano[3,4- b]indole based inhibitors of HCV NS5B polymerase. Further exploration of the allosteric binding site led to the discovery of the significantly more potent compound 12.