1.
Bioorg Med Chem Lett
; 13(22): 4059-63, 2003 Nov 17.
Article
in English
| MEDLINE
| ID: mdl-14592508
ABSTRACT
Tetrapeptide-based peptidomimetic compounds have been shown to effectively inhibit the hepatitis C virus NS3.4A protease without the need of a charged functionality. An aldehyde is used as a prototype reversible electrophilic warhead. The SAR of the P1 and P2 inhibitor positions is discussed.
Subject(s)
Hepacivirus/enzymology , Oligopeptides/chemical synthesis , Oligopeptides/pharmacology , Protease Inhibitors/chemical synthesis , Hepacivirus/drug effects , Kinetics , Models, Molecular , Protease Inhibitors/pharmacology , Protein Conformation , Structure-Activity Relationship , X-Ray Diffraction
2.
Bioorg Med Chem Lett
; 14(6): 1441-6, 2004 Mar 22.
Article
in English
| MEDLINE
| ID: mdl-15006379
ABSTRACT
The alpha-ketoamide warhead (e.g., 15) was found to be a practical replacement for aliphatic aldehydes in a series of HCV NS3.4A protease inhibitors. Structure-activity relationships and prime side optimization are discussed.