Identification of novel epoxide inhibitors of hepatitis C virus replication using a high-throughput screen.
Using our high-throughput hepatitis C replicon assay to screen a library of over 8,000 novel diversity-oriented synthesis (DOS) compounds, we identified several novel compounds that regulate hepatitis C virus (HCV) replication, including two libraries of epoxides that inhibit HCV replication (best 50% effective concentration, < 0.5 microM). We then synthesized an analog of these compounds with optimized activity.
GI Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
Lee F
LF
Peng
Sun Suk
SS
Kim
Sirinya
S
Matchacheep
Xiaoguang
X
Lei
Shun
S
Su
Wenyu
W
Lin
Weerawat
W
Runguphan
Won-Hyeok
WH
Choe
Naoya
N
Sakamoto
Masanori
M
Ikeda
Nobuyuki
N
Kato
Aaron B
AB
Beeler
John A
JA
Porco
Stuart L
SL
Schreiber
Raymond T
RT
Chung
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D003198:Computer Simulation; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004852:Epoxy Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D016174:Hepacivirus / Q000187:drug effects*; D008301:Maleimides / Q000494:pharmacology; D012093:Replicon / Q000187:drug effects; D015203:Reproducibility of Results; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D004852:Epoxy Compounds; D008301:Maleimides; C043592:maleimide