Discovery of 4H-pyrazolo[1,5-a]pyrimidin-7-ones as potent inhibitors of hepatitis C virus polymerase

Yongqi Deng; Gerald W Shipps Jr; Tong Wang; Janeta Popovici-Muller; Kristin E Rosner; M Arshad Siddiqui; Jose Duca; Alan B Cooper; Michael Cable

doi:10.1016/j.bmcl.2009.07.124

Discovery of 4H-pyrazolo[1,5-a]pyrimidin-7-ones as potent inhibitors of hepatitis C virus polymerase

Bioorg Med Chem Lett. 2009 Sep 15;19(18):5363-7. doi: 10.1016/j.bmcl.2009.07.124. Epub 2009 Aug 6.

Authors

Yongqi Deng¹, Gerald W Shipps Jr, Tong Wang, Janeta Popovici-Muller, Kristin E Rosner, M Arshad Siddiqui, Jose Duca, Alan B Cooper, Michael Cable

Affiliation

¹ Schering-Plough Research Institute Cambridge, 320 Bent Street, Cambridge, MA 02141, United States. [email protected]

PMID: 19682898
DOI: 10.1016/j.bmcl.2009.07.124

Abstract

A series of 4H-pyrazolo[1,5-a]pyrimidin-7-one derivatives was synthesized and evaluated for inhibitory activity against HCV NS5B RNA-dependent RNA polymerase. A number of these compounds exhibited potent activity in enzymatic assay. The synthesis and structure-activity relationship are also described.

MeSH terms

Antiviral Agents / chemistry
Antiviral Agents / pharmacology*
Hepacivirus / enzymology*
Models, Molecular
Protein Binding
Pyrazoles / chemistry
Pyrazoles / pharmacology*
Pyrimidines / chemistry
Pyrimidines / pharmacology*
RNA-Dependent RNA Polymerase / antagonists & inhibitors
RNA-Dependent RNA Polymerase / metabolism
Structure-Activity Relationship
Viral Nonstructural Proteins / antagonists & inhibitors*
Viral Nonstructural Proteins / metabolism*

Substances

Antiviral Agents
Pyrazoles
Pyrimidines
Viral Nonstructural Proteins
NS-5 protein, hepatitis C virus
RNA-Dependent RNA Polymerase