Solution and solid-phase synthesis of potent inhibitors of hepatitis C virus NS3 proteinase.
A versatile route for the synthesis of homochiral alpha-ketoamide analogues of amino acids is described. Incorporation of this functionality into peptide sequences using either solution or solid-phase chemistry resulted in potent inhibitors of the Hepatitis C Virus NS3 proteinase.
Beevers
Rebekah
R
Department of Chemistry, Roche Discovery Welwyn, 40 Broadwater Road, Welwyn Garden City, AL7 3AY, Hertfordshire, UK.
Carr
Maria G
MG
Jones
Philip S
PS
Jordan
Steven
S
Kay
Paul B
PB
Lazell
Robert C
RC
Raynham
Tony M
TM
D000596:Amino Acids; D020650:Combinatorial Chemistry Techniques; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D005449:Fluorenes; D016174:Hepacivirus / Q000201:enzymology; D006801:Humans; D020128:Inhibitory Concentration 50; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D000596:Amino Acids; D004791:Enzyme Inhibitors; D005449:Fluorenes; D009842:Oligopeptides; D017361:Viral Nonstructural Proteins; C016456:N(alpha)-fluorenylmethyloxycarbonylamino acids; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases