title: Discovery of pyrano[3,4-b]indoles as potent and selective HCV NS5B polymerase inhibitors.
abstract: A novel series of HCV NS5B RNA-dependent RNA polymerase inhibitors containing a pyrano[3,4-b]indole scaffold is described leading to the discovery of compound 16, a highly potent and selective inhibitor that is active in the replicon system.
authors.affiliation: Chemical and Screening Sciences and Infectious Diseases, Wyeth Research, Pearl River, New York 10965, USA. gopalsa@wyeth.com
authors.forename: Ariamala
authors.initials: A
authors.lastname: Gopalsamy
authors.forename: Kitae
authors.initials: K
authors.lastname: Lim
authors.forename: Gregory
authors.initials: G
authors.lastname: Ciszewski
authors.forename: Kaapjoo
authors.initials: K
authors.lastname: Park
authors.forename: John W
authors.initials: JW
authors.lastname: Ellingboe
authors.forename: Jonathan
authors.initials: J
authors.lastname: Bloom
authors.forename: Shabana
authors.initials: S
authors.lastname: Insaf
authors.forename: Janis
authors.initials: J
authors.lastname: Upeslacis
authors.forename: Tarek S
authors.initials: TS
authors.lastname: Mansour
authors.forename: Girija
authors.initials: G
authors.lastname: Krishnamurthy
authors.forename: Murthy
authors.initials: M
authors.lastname: Damarla
authors.forename: Yelena
authors.initials: Y
authors.lastname: Pyatski
authors.forename: Douglas
authors.initials: D
authors.lastname: Ho
authors.forename: Anita Y M
authors.initials: AY
authors.lastname: Howe
authors.forename: Mark
authors.initials: M
authors.lastname: Orlowski
authors.forename: Boris
authors.initials: B
authors.lastname: Feld
authors.forename: John
authors.initials: J
authors.lastname: O'Connell
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry; D018360:Crystallography, X-Ray; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D016174:Hepacivirus / Q000201:enzymology*; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry; D011714:Pyrans / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D012321:DNA-Directed RNA Polymerases; D007211:Indoles; D011714:Pyrans; D017361:Viral Nonstructural Proteins; C495221:(5-cyano-8-methyl-1-propyl-1,3,4,9-tetrahydropyrano(3,4-b)indol-1-yl)acetic acid; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase