P1 Phenethyl peptide boronic acid inhibitors of HCV NS3 protease.
A series of peptide boronic acids containing extended, hydrophobic P1 residues was prepared to probe the shallow, hydrophobic S1 region of HCV NS3 protease. The p-trifluoromethylphenethyl P1 substituent was identified as optimal with respect to inhibitor potency for NS3 and selectivity against elastase and chymotrypsin.
Priestley
E Scott
ES
Bristol-Myers Squibb Pharmaceutical Research Institute, Experimental Station, Wilmington,DE 19880-0500, USA. scott.priestley@bms.com
De Lucca
Indawati
I
Ghavimi
Bahman
B
Erickson-Viitanen
Susan
S
Decicco
Carl P
CP
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001897:Boronic Acids / Q000138:chemical synthesis* / Q000494:pharmacology*; D002918:Chymotrypsin / Q000037:antagonists & inhibitors; D016174:Hepacivirus / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D007202:Indicators and Reagents; D007962:Leukocytes / Q000187:drug effects / Q000201:enzymology; D010179:Pancreas / Q000201:enzymology; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors; D010455:Peptides / Q000138:chemical synthesis* / Q000494:pharmacology*; D011480:Protease Inhibitors / 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
D000998:Antiviral Agents; D001897:Boronic Acids; D002918:Chymotrypsin; D007202:Indicators and Reagents; D010196:Pancreatic Elastase; D010455:Peptides; 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