Pyrazolo[1,5- a]pyrimidine-based inhibitors of HCV polymerase

Synthesis and optimization of novel pyrazolo[1,5- a]pyrimidine HCV polymerase inhibitors are described. 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...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2009-11, Vol.19 (22), p.6331-6336
Main Authors: Popovici-Muller, Janeta, Shipps, Gerald W., Rosner, Kristin E., Deng, Yongqi, Wang, Tong, Curran, Patrick J., Brown, Meredith A., Siddiqui, M. Arshad, Cooper, Alan B., Duca, José, Cable, Michael, Girijavallabhan, Viyyoor
Format: Article
Language:English
Subjects:
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antiviral agents
Biological and medical sciences
DNA-Directed RNA Polymerases - antagonists & inhibitors
Drug Evaluation, Preclinical
Enzyme Inhibitors - pharmacology
HCV polymerase inhibitors
Hepacivirus
Hepatitis C - enzymology
Hepatitis C - virology
Hepatitis C virus
Inhibitory Concentration 50
Medical sciences
Molecular Weight
Pharmacology. Drug treatments
Pyrazoles - pharmacology
Pyrimidines - pharmacology
RNA Replicase - antagonists & inhibitors
RNA, Viral - drug effects
Small Molecule Libraries
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Summary:Synthesis and optimization of novel pyrazolo[1,5- a]pyrimidine HCV polymerase inhibitors are described. 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.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2009.09.087