Discovery of 4H-pyrazolo[1,5-a]pyrimidin-7-ones as potent inhibitors of hepatitis C virus polymerase.
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.
Deng
Yongqi
Y
Schering-Plough Research Institute Cambridge, 320 Bent Street, Cambridge, MA 02141, United States. yongqi.deng@spcorp.com
Shipps
Gerald W
GW
Wang
Tong
T
Popovici-Muller
Janeta
J
Rosner
Kristin E
KE
Siddiqui
M Arshad
MA
Duca
Jose
J
Cooper
Alan B
AB
Cable
Michael
M
D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D016174:Hepacivirus / Q000201:enzymology*; D008958:Models, Molecular; D011485:Protein Binding; D011720:Pyrazoles / Q000737:chemistry / Q000494:pharmacology*; D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology*; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*
D000998:Antiviral Agents; D011720:Pyrazoles; D011743:Pyrimidines; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase