Substituted tetrahydro-beta-carbolines as potential agents for the treatment of human papillomavirus infection.
The identification and optimization of a series of substituted tetrahydro-beta-carbolines with potent activity against human papillomavirus is described. Structure-activity studies focused on the substitution pattern and chirality of the beta-carboline ring system are discussed. Optimization of these parameters led to compounds with antiviral activities in the low nanomolar range.
Miller
John F
JF
Department of Medicinal Chemistry, Infectious Diseases Center for Excellence in Drug Discovery, GlaxoSmithKline Research and Development, Five Moore Drive, Research Triangle Park, NC 27709-3398, USA. john.6.miller@gsk.com
Turner
Elizabeth M
EM
Sherrill
Ronald G
RG
Gudmundsson
Kristjan
K
Spaltenstein
Andrew
A
Sethna
Phiroze
P
Brown
Kevin W
KW
Harvey
Robert
R
Romines
Karen R
KR
Golden
Pamela
P
D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D002243:Carbolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D002460:Cell Line; D006801:Humans; D051379:Mice; D030361:Papillomavirus Infections / Q000188:drug therapy; D013329:Structure-Activity Relationship
D000998:Antiviral Agents; D002243:Carbolines