Hepatitis C virus NS3 protease inhibitors comprising a novel aromatic P1 moiety.
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.
Rönn
Robert
R
Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry, Uppsala University, BMC, Box 574, SE-751 23 Uppsala, Sweden.
Lampa
Anna
A
Peterson
Shane D
SD
Gossas
Thomas
T
Akerblom
Eva
E
Danielson
U Helena
UH
Karlén
Anders
A
Sandström
Anja
A
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
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