title: Substituted tetrahydrocarbazoles with potent activity against human papillomaviruses.
abstract: The synthesis and SAR of a series of substituted 1-aminotetrahydrocarbazoles with potent activity against human papillomaviruses are described. Synthetic approaches allowing for variation of the substitution pattern of the tetrahydrocarbazole are outlined and resulting changes in antiviral activity are highlighted. Several compounds with in vitro antiviral activity (W12 antiviral assay) in the low nanomolar range were identified and (1R)-6-bromo-N-[(1R)-1-phenylethyl]-2,3,4,9-tetrahydro-1H-carbazole-1-amine was selected for further evaluation.
authors.affiliation: Department of Medicinal Chemistry, Infectious Diseases Center of Excellence for Drug Discovery, GlaxoSmithKline Research and Development, Five Moore Drive, Research Triangle Park, NC 27709-3398, USA. ksgmjl@aol.com
authors.forename: Kristjan S
authors.initials: KS
authors.lastname: Gudmundsson
authors.forename: Paul R
authors.initials: PR
authors.lastname: Sebahar
authors.forename: Leah D'Aurora
authors.initials: LD
authors.lastname: Richardson
authors.forename: John G
authors.initials: JG
authors.lastname: Catalano
authors.forename: Sharon D
authors.initials: SD
authors.lastname: Boggs
authors.forename: Andrew
authors.initials: A
authors.lastname: Spaltenstein
authors.forename: Phiroze B
authors.initials: PB
authors.lastname: Sethna
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Brown
authors.forename: Robert
authors.initials: R
authors.lastname: Harvey
authors.forename: Karen R
authors.initials: KR
authors.lastname: Romines
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D002227:Carbazoles / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D002460:Cell Line; D004279:DNA, Viral / Q000187:drug effects; D005260:Female; D006801:Humans; D027383:Papillomaviridae / Q000187:drug effects*; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D000998:Antiviral Agents; D002227:Carbazoles; D004279:DNA, Viral