1. Pyrazolo[1,5-a]pyrimidine-based inhibitors of HCV polymerase.
- Author
-
Popovici-Muller J, Shipps GW Jr, Rosner KE, Deng Y, Wang T, Curran PJ, Brown MA, Siddiqui MA, Cooper AB, Duca J, Cable M, and Girijavallabhan V
- Subjects
- Drug Evaluation, Preclinical, Hepacivirus, Hepatitis C virology, Inhibitory Concentration 50, Molecular Weight, Small Molecule Libraries, DNA-Directed RNA Polymerases antagonists & inhibitors, Enzyme Inhibitors pharmacology, Hepatitis C enzymology, Pyrazoles pharmacology, Pyrimidines pharmacology, RNA, Viral drug effects, RNA-Dependent RNA Polymerase antagonists & inhibitors
- 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.
- Published
- 2009
- Full Text
- View/download PDF