Design and efficient synthesis of novel arylthiourea derivatives as potent hepatitis C virus inhibitors.
A novel class of arylthiourea HCV inhibitors bearing various functionalities, such as cyclic urea, cyclic thiourea, urea, and thiourea, on the alkyl linker were designed and synthesized. Herein we report the synthesis and structure-activity relationships (SARs) of this novel class of arylthiourea derivatives that showed potent inhibitory activities against HCV in the cell-based subgenomic HCV replicon assay. Among compounds tested, the new carbazole derivative 64, which has an eight-carbon linkage between the phenyl and carbazole rings and a tolyl group at the N-9 position of carbazole, was found to possess strong anti-HCV activity (EC50=0.031 microM), lower cytotoxicity (CC50 >50 microM), and higher selectivity index (SI >1612) compared to its derivatives.
Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, No. 35, Keyan Road, Zhunan Town, Miaoli County 350, Taiwan, ROC.
Iou-Jiun
IJ
Kang
Li-Wen
LW
Wang
Sheng-Ju
SJ
Hsu
Chung-Chi
CC
Lee
Yen-Chun
YC
Lee
Yen-Shian
YS
Wu
Andrew
A
Yueh
Jing-Chyi
JC
Wang
Tsu-An
TA
Hsu
Yu-Sheng
YS
Chao
Jyh-Haur
JH
Chern
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D002227:Carbazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D015195:Drug Design; D016174:Hepacivirus / Q000187:drug effects*; D006801:Humans; D013329:Structure-Activity Relationship; D013890:Thiourea / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D002227:Carbazoles; D013890:Thiourea