title: Identification of [(naphthalene-1-carbonyl)-amino]-acetic acid derivatives as nonnucleoside inhibitors of HCV NS5B RNA dependent RNA polymerase.
abstract: A novel series of HCV NS5B RNA dependent RNA polymerase inhibitors containing a naphthalene carboxamide scaffold were identified by high throughput screening. Optimization of substituents by parallel synthesis and the iterative design towards understanding structure-activity relationship to improve potency are described. Tetra substituted naphthalene 31 displayed potent activity with IC(50) of 120 nM against HCV NS5B enzyme and was selective over a panel of polymerases.
authors.affiliation: Chemical and Screening Sciences, Wyeth Research, 401 N Middletown Road, Pearl River, NY 10965, USA. gopalsa@wyeth.com
authors.forename: Ariamala
authors.initials: A
authors.lastname: Gopalsamy
authors.forename: Kitae
authors.initials: K
authors.lastname: Lim
authors.forename: John W
authors.initials: JW
authors.lastname: Ellingboe
authors.forename: Girija
authors.initials: G
authors.lastname: Krishnamurthy
authors.forename: Mark
authors.initials: M
authors.lastname: Orlowski
authors.forename: Boris
authors.initials: B
authors.lastname: Feld
authors.forename: Marja
authors.initials: M
authors.lastname: van Zeijl
authors.forename: Anita Y M
authors.initials: AY
authors.lastname: Howe
mesh_terms: D000085:Acetates / Q000737:chemistry* / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*
chemical_list: D000085:Acetates; D004791:Enzyme Inhibitors; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase