title: Structure-activity relationship (SAR) studies of quinoxalines as novel HCV NS5B RNA-dependent RNA polymerase inhibitors.
abstract: From chemical compound library screening using an HCV NS5B RNA-dependent RNA polymerase enzymatic assay, we identified a substituted quinoxaline hit with an IC(50) of 5.5 microM. A series of substituted quinoxaline amide derivatives were synthesized based on the hit's pharmacophore, and a good structure-activity relationship was observed. Computer modeling analysis was employed to help comprehend the SAR.
authors.affiliation: Drug Discovery, Valeant Pharmaceutical Research & Development, 3300 Hyland Avenue, Costa Mesa, CA 92626, USA. frong@ardeabiosciences.com
authors.forename: Frank
authors.initials: F
authors.lastname: Rong
authors.forename: Suetying
authors.initials: S
authors.lastname: Chow
authors.forename: Shunqi
authors.initials: S
authors.lastname: Yan
authors.forename: Gary
authors.initials: G
authors.lastname: Larson
authors.forename: Zhi
authors.initials: Z
authors.lastname: Hong
authors.forename: Jim
authors.initials: J
authors.lastname: Wu
mesh_terms: D003198:Computer Simulation; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D007202:Indicators and Reagents; D008958:Models, Molecular; D011485:Protein Binding; D011810:Quinoxalines / Q000138:chemical synthesis* / Q000494:pharmacology*; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*
chemical_list: D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D011810:Quinoxalines; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase