title: Pyrazolo[1,5-a]pyrimidine-based inhibitors of HCV polymerase.
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.
authors.affiliation: Schering-Plough Research Institute Cambridge, 320 Bent Street, Cambridge, MA 02141, USA. janeta.popovici-muller@spcorp.com
authors.forename: Janeta
authors.initials: J
authors.lastname: Popovici-Muller
authors.forename: Gerald W
authors.initials: GW
authors.lastname: Shipps
authors.forename: Kristin E
authors.initials: KE
authors.lastname: Rosner
authors.forename: Yongqi
authors.initials: Y
authors.lastname: Deng
authors.forename: Tong
authors.initials: T
authors.lastname: Wang
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Curran
authors.forename: Meredith A
authors.initials: MA
authors.lastname: Brown
authors.forename: M Arshad
authors.initials: MA
authors.lastname: Siddiqui
authors.forename: Alan B
authors.initials: AB
authors.lastname: Cooper
authors.forename: José
authors.initials: J
authors.lastname: Duca
authors.forename: Michael
authors.initials: M
authors.lastname: Cable
authors.forename: Viyyoor
authors.initials: V
authors.lastname: Girijavallabhan
mesh_terms: 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
chemical_list: 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