Design and synthesis of potent, non-peptide inhibitors of HCV NS3 protease.
Starting from a hexapeptide boronic acid lead, 3-amino bicyclic pyrazinones as novel beta-sheet dipeptide mimetics have been designed and synthesized. Side-chain manipulation of this scaffold generated a series of potent, nonpeptidic inhibitors of HCV NS3 protease.
Zhang
Xiaojun
X
Discovery Chemistry, Bristol-Myers Squibb, Route 141 and Henry Clay Road, Wilmington, DE 19880, USA. xiaojun.zhang@bms.com
Schmitt
Aaron C
AC
Jiang
Wen
W
Wasserman
Zelda
Z
Decicco
Carl P
CP
D018360:Crystallography, X-Ray; D016174:Hepacivirus / Q000187:drug effects / Q000201:enzymology*; D008958:Models, Molecular; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000737:chemistry*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
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