Tetrahydrocarbazole amides with potent activity against human papillomaviruses.
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.
Gudmundsson
Kristjan S
KS
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
Boggs
Sharon D
SD
Sebahar
Paul R
PR
Richardson
Leah D'Aurora
LD
Spaltenstein
Andrew
A
Golden
Pamela
P
Sethna
Phiroze B
PB
Brown
Kevin W
KW
Moniri
Kelly
K
Harvey
Robert
R
Romines
Karen R
KR
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
D000577:Amides; D000998:Antiviral Agents; D002227:Carbazoles; D003577:Cytochrome P-450 Enzyme System