Abstract
Aseries of indole acrylamide derivatives were synthesized and evaluated for their inhibitory effects on hepatitis C virus (HCV) replication. Previously, we have identified (E)-N-(4- tert-butylphenyl)-3-(5-cyano-1H-indol-3-yl)-2-methylacrylamide (6c) as one of the promising leads for anti-HCV chemotherapy. Based on the structural features of indole acrylamide, we have explored extended structure-activity relationship study using analogs with substituted indoles, various amides, and N-substitution at the indole ring. Among the newly synthesized series, 5-cyanoindole acrylamide analog with N-acetyl substitution (13c ) (EC50 = 0.98 μM, CC 50 = 40.74 μM, and SI = 41.6) exhibited the most potent antiviral activity with reasonable cytotoxicity in a cell-based J6/JFH1 reporter assay using Huh7.5 cells. In addition, improved water solubility of 13c compared to 6c further merits consideration of 13c as a valuable candidate for anti-HCV therapeutics development.
Original language | English |
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Pages (from-to) | 88-98 |
Number of pages | 11 |
Journal | Bulletin of the Korean Chemical Society |
Volume | 36 |
Issue number | 1 |
DOIs | |
State | Published - 20 Jan 2015 |
Keywords
- Hcv replication inhibitors
- Hepatitis c virus
- Indole derivatives
- Structure-activity relationship (sar) study