title: The discovery and structure-activity relationships of pyrano[3,4-b]indole-based inhibitors of hepatitis C virus NS5B polymerase.
abstract: We describe the structure-activity relationship of the C7-position 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 compounds 13 and 14.
authors.affiliation: VenatoRx Pharmaceuticals Inc., 700 Pennsylvania Drive, Exton, PA 19341, USA. jackson@venatorx.com
authors.forename: Randy W
authors.initials: RW
authors.lastname: Jackson
authors.forename: Matthew G
authors.initials: MG
authors.lastname: LaPorte
authors.forename: Torsten
authors.initials: T
authors.lastname: Herbertz
authors.forename: Tandy L
authors.initials: TL
authors.lastname: Draper
authors.forename: Janet A
authors.initials: JA
authors.lastname: Gaboury
authors.forename: Susan R
authors.initials: SR
authors.lastname: Rippin
authors.forename: Ravi
authors.initials: R
authors.lastname: Patel
authors.forename: Srinivas K
authors.initials: SK
authors.lastname: Chunduru
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Benetatos
authors.forename: Dorothy C
authors.initials: DC
authors.lastname: Young
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Burns
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Condon
mesh_terms: D000495:Allosteric Site; D018360:Crystallography, X-Ray; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D016174:Hepacivirus / Q000187:drug effects* / Q000201:enzymology*; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015394:Molecular Structure; D011714:Pyrans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D004791:Enzyme Inhibitors; D007211:Indoles; D011714:Pyrans; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase