title: Design, synthesis, and in vitro evaluation of potential West Nile virus protease inhibitors based on the 1-oxo-1,2,3,4-tetrahydroisoquinoline and 1-oxo-1,2-dihydroisoquinoline scaffolds.
abstract: The 1-oxo-1, 2, 3, 4-tetrahydroisoquinoline and 1-Oxo-1, 2-dihydroisoquinoline scaffolds were utilized in the design and solution phase synthesis of focused libraries of compounds for screening against West Nile Virus (WNV) protease. Exploratory studies have led to the identification of a WNV protease inhibitor (a 1-oxo-1, 2-dihydroisoquinoline-based derivative, 12j) which could potentially serve as a launching pad for a hit-to-lead optimization campaign. The identified hit was devoid of any inhibitory activity toward a panel of mammalian serine proteases.
authors.affiliation: Department of Chemistry, Wichita State University, Wichita, Kansas 67260, USA.
authors.forename: Dengfeng
authors.initials: D
authors.lastname: Dou
authors.forename: Prasanth
authors.initials: P
authors.lastname: Viwanathan
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Guijia
authors.initials: G
authors.lastname: He
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Alliston
authors.forename: Gerald H
authors.initials: GH
authors.lastname: Lushington
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Brown-Clay
authors.forename: R
authors.initials: R
authors.lastname: Padmanabhan
authors.forename: William C
authors.initials: WC
authors.lastname: Groutas
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D015195:Drug Design; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D044005:Tetrahydroisoquinolines / Q000737:chemistry* / Q000494:pharmacology; D014902:West Nile virus / Q000187:drug effects / Q000201:enzymology*
chemical_list: D000998:Antiviral Agents; D011480:Protease Inhibitors; D044005:Tetrahydroisoquinolines; C014843:1,2,3,4-tetrahydroisoquinoline