Abstract
The present paper describes a novel series of HCV RNA polymerase inhibitors based on a pyrazolo[1,5-a]pyrimidine scaffold bearing hydrophobic groups and an acidic functionality. Several compounds were optimized to low nanomolar potencies in a biochemical RdRp assay. SAR trends clearly reveal a stringent preference for a cyclohexyl group as one of the hydrophobes, and improved activities for carboxylic acid derivatives.
MeSH terms
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DNA-Directed RNA Polymerases / antagonists & inhibitors*
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Drug Evaluation, Preclinical
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Enzyme Inhibitors / pharmacology*
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Hepacivirus
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Hepatitis C / enzymology*
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Hepatitis C / virology
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Inhibitory Concentration 50
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Molecular Weight
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Pyrazoles / pharmacology*
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Pyrimidines / pharmacology*
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RNA, Viral / drug effects*
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RNA-Dependent RNA Polymerase / antagonists & inhibitors*
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Small Molecule Libraries
Substances
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Enzyme Inhibitors
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Pyrazoles
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Pyrimidines
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RNA, Viral
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Small Molecule Libraries
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pyrazolo(1,5-a)pyrimidine
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RNA-Dependent RNA Polymerase
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DNA-Directed RNA Polymerases