Substituted tetrahydrocarbazoles with potent activity against human papillomaviruses.
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.
Gudmundsson
Kristjan S
KS
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
Sebahar
Paul R
PR
Richardson
Leah D'Aurora
LD
Catalano
John G
JG
Boggs
Sharon D
SD
Spaltenstein
Andrew
A
Sethna
Phiroze B
PB
Brown
Kevin W
KW
Harvey
Robert
R
Romines
Karen R
KR
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
D000998:Antiviral Agents; D002227:Carbazoles; D004279:DNA, Viral