title: Hepatitis C virus NS3 protease inhibitors comprising a novel aromatic P1 moiety.
abstract: Inhibition of the hepatitis C virus (HCV) NS3 protease has emerged as an attractive approach to defeat the global hepatitis C epidemic. In this work, we present the synthesis and biochemical evaluation of HCV NS3 protease inhibitors comprising a non-natural aromatic P(1) moiety. A series of inhibitors with aminobenzoyl sulfonamides displaying submicromolar potencies in the full-length NS3 protease assay was prepared through a microwave-irradiated, palladium-catalyzed, amidocarbonylation protocol.
authors.affiliation: Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry, Uppsala University, BMC, Box 574, SE-751 23 Uppsala, Sweden.
authors.forename: Robert
authors.initials: R
authors.lastname: Rönn
authors.forename: Anna
authors.initials: A
authors.lastname: Lampa
authors.forename: Shane D
authors.initials: SD
authors.lastname: Peterson
authors.forename: Thomas
authors.initials: T
authors.lastname: Gossas
authors.forename: Eva
authors.initials: E
authors.lastname: Akerblom
authors.forename: U Helena
authors.initials: UH
authors.lastname: Danielson
authors.forename: Anders
authors.initials: A
authors.lastname: Karlén
authors.forename: Anja
authors.initials: A
authors.lastname: Sandström
mesh_terms: D008872:Microwaves; D010165:Palladium; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry* / Q000494:pharmacology*; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; D000096926:Benzenesulfonamides
chemical_list: D010165:Palladium; D015842:Serine Proteinase Inhibitors; D013449:Sulfonamides; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C009720:2-aminobenzenesulfonamide; D000096926:Benzenesulfonamides