title: Novel thiazolones as HCV NS5B polymerase allosteric inhibitors: Further designs, SAR, and X-ray complex structure.
abstract: Structure-activity relationships (SAR) of 1 against HCV NS5B polymerase were described. SAR explorations and further structure-based design led to the identifications of 2 and 3 as novel HCV NS5B inhibitors. X-ray structure of 3 in complex with NS5B polymerase was obtained at a resolution of 2.2A, and confirmed the design.
authors.affiliation: Valeant Pharmaceuticals Research and Development, 3300 Hyland Ave., Costa Mesa, CA 92626, USA. syan@valeant.com
authors.forename: Shunqi
authors.initials: S
authors.lastname: Yan
authors.forename: Gary
authors.initials: G
authors.lastname: Larson
authors.forename: Jim Z
authors.initials: JZ
authors.lastname: Wu
authors.forename: Todd
authors.initials: T
authors.lastname: Appleby
authors.forename: Yili
authors.initials: Y
authors.lastname: Ding
authors.forename: Robert
authors.initials: R
authors.lastname: Hamatake
authors.forename: Zhi
authors.initials: Z
authors.lastname: Hong
authors.forename: Nanhua
authors.initials: N
authors.lastname: Yao
mesh_terms: D000494:Allosteric Regulation; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D008968:Molecular Conformation; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry* / Q000494:pharmacology*; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D013844:Thiazoles; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase