Parallel synthesis of 5-cyano-6-aryl-2-thiouracil derivatives as inhibitors for hepatitis C viral NS5B RNA-dependent RNA polymerase.
From random screening of our compound libraries, we identified a hit compound with an IC50 of 27 microM against hepatitis C viral NS5B RNA-dependent RNA polymerase. By using a parallel synthetic strategy, a series of its derivatives were synthesized. From their anti-HCV activity screening, compounds with single digital 3.8 micromolar activity were obtained.
Ding
Yili
Y
Valeant Pharmaceuticals International, 3300 Hyland Avenue Costa Mesa, CA 92626, USA. yding@valeant.com
Girardet
Jean-Luc
JL
Smith
Kenneth L
KL
Larson
Gary
G
Prigaro
Brett
B
Wu
Jim Z
JZ
Yao
Nanhua
N
D000998:Antiviral Agents / Q000138:chemical synthesis / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D016174:Hepacivirus / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000378:metabolism*; D020128:Inhibitory Concentration 50; D011725:Pyridines / Q000138:chemical synthesis* / Q000378:metabolism*; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D014498:Uracil / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
C509881:2-Pyridin-2-yl-1H-indole; D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D007211:Indoles; D011725:Pyridines; D017361:Viral Nonstructural Proteins; C056431:5-cyanouracil; D014498:Uracil; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase