title: Glycine alpha-ketoamides as HCV NS3 protease inhibitors.
abstract: Using a tetrapeptide-based alpha-ketoamide template, various amines and amino acids were incorporated to explore the prime side of the HCV NS3 protease catalytic site. Glycine carboxylic acid was found to be the most effective prime group. Further optimization yielded an inhibitor with IC(50) of 0.060 microM.
authors.affiliation: Department of Discovery Chemistry, Pharmaceutical Research Institute, Bristol-Myers Squibb Company, PO Box 5400, Princeton, NJ 08543, USA. wei.han1@bms.com
authors.forename: Wei
authors.initials: W
authors.lastname: Han
authors.forename: Zilun
authors.initials: Z
authors.lastname: Hu
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Jiang
authors.forename: Zelda R
authors.initials: ZR
authors.lastname: Wasserman
authors.forename: Carl P
authors.initials: CP
authors.lastname: Decicco
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000494:pharmacology*; D000588:Amines / Q000737:chemistry; D000596:Amino Acids / Q000737:chemistry; D001665:Binding Sites; D005998:Glycine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology*; D016174:Hepacivirus / Q000201:enzymology*; D011480:Protease Inhibitors / Q000138:chemical synthesis*; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000378:metabolism*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000577:Amides; D000588:Amines; D000596:Amino Acids; D005998:Glycine; D011480:Protease 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; C478046:glycine alpha-ketoamide