title: Tetrahydrocarbazole amides with potent activity against human papillomaviruses.
abstract: Synthesis of a series of tetrahydrocarbazole amides with potent activity against human papillomaviruses is described. Synthetic approaches allowing for variation of the substitution pattern of the tetrahydrocarbazole and the amide are outlined and resulting changes in antiviral activity and certain developability parameters are highlighted. Several compounds with in vitro antiviral activity (W12 antiviral assay) in the single digit nanomolar range were identified and N-[(1R)-6-chloro-2,3,4,9-tetrahydro-1H-carbazol-1-yl]-2-pyridinecarboxamide was selected for further evaluation.
authors: Department of Medicinal Chemistry, Infectious Diseases Center of Excellence for Drug Discovery, GlaxoSmithKline Research & Development, Five Moore Drive, Research Triangle Park, NC 27709-3398, USA. ksgudmundsson@gmail.com
authors: Kristjan S
authors: KS
authors: Gudmundsson
authors: Sharon D
authors: SD
authors: Boggs
authors: Paul R
authors: PR
authors: Sebahar
authors: Leah D'Aurora
authors: LD
authors: Richardson
authors: Andrew
authors: A
authors: Spaltenstein
authors: Pamela
authors: P
authors: Golden
authors: Phiroze B
authors: PB
authors: Sethna
authors: Kevin W
authors: KW
authors: Brown
authors: Kelly
authors: K
authors: Moniri
authors: Robert
authors: R
authors: Harvey
authors: Karen R
authors: KR
authors: Romines
mesh_terms: D000284:Administration, Oral; D000577:Amides / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000494:pharmacology; D002227:Carbazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D002522:Chlorocebus aethiops; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry; D004285:Dogs; D000882:Haplorhini; D006801:Humans; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D027383:Papillomaviridae / Q000378:metabolism*; D051381:Rats; D014709:Vero Cells
chemical_list: D000577:Amides; D000998:Antiviral Agents; D002227:Carbazoles; D003577:Cytochrome P-450 Enzyme System