Pyrazolo[1,5-a]pyrimidine-based inhibitors of HCV polymerase.
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.
Popovici-Muller
Janeta
J
Schering-Plough Research Institute Cambridge, 320 Bent Street, Cambridge, MA 02141, USA. janeta.popovici-muller@spcorp.com
Shipps
Gerald W
GW
Rosner
Kristin E
KE
Deng
Yongqi
Y
Wang
Tong
T
Curran
Patrick J
PJ
Brown
Meredith A
MA
Siddiqui
M Arshad
MA
Cooper
Alan B
AB
Duca
José
J
Cable
Michael
M
Girijavallabhan
Viyyoor
V
D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors*; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D016174:Hepacivirus; D006526:Hepatitis C / Q000201:enzymology* / Q000821:virology; D020128:Inhibitory Concentration 50; D008970:Molecular Weight; D011720:Pyrazoles / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D012367:RNA, Viral / Q000187:drug effects*; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors*; D054852:Small Molecule Libraries
D004791:Enzyme Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; D012367:RNA, Viral; D054852:Small Molecule Libraries; C527752:pyrazolo(1,5-a)pyrimidine; D012324:RNA-Dependent RNA Polymerase; D012321:DNA-Directed RNA Polymerases