Alpha-ketoamides, alpha-ketoesters and alpha-diketones as HCV NS3 protease inhibitors.
Peptide-based alpha-ketoamides, alpha-ketoesters and alpha-diketones were designed, synthesized and evaluated against HCV NS3 protease. Alpha-ketoamides have the highest affinity among the three classes, with 8 being the most potent inhibitor with an IC50 of 340 nM.
Han
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Department of Chemical and Physical Sciences, DuPont Pharmaceuticals Company, Wilmington, DE 19880, USA. wei.han@dupontpharma.com
Hu
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Jiang
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Decicco
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CP
D000577:Amides / Q000737:chemistry; D000595:Amino Acid Sequence; D004952:Esters / Q000737:chemistry; D016174:Hepacivirus / Q000187:drug effects / Q000378:metabolism; D007659:Ketones / Q000737:chemistry / Q000494:pharmacology*; D015842:Serine Proteinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D017361:Viral Nonstructural Proteins / Q000494:pharmacology*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D000577:Amides; D004952:Esters; D007659:Ketones; D015842:Serine Proteinase Inhibitors; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases