Bioorganic & Medicinal Chemistry Letters 2000-10-16

Highly potent and selective peptide-based inhibitors of the hepatitis C virus serine protease: towards smaller inhibitors.

M Llinàs-Brunet, M Bailey, G Fazal, E Ghiro, V Gorys, S Goulet, T Halmos, R Maurice, M Poirier, M A Poupart, J Rancourt, D Thibeault, D Wernic, D Lamarre

Index: Bioorg. Med. Chem. Lett. 10 , 2267, (2000)

Full Text: HTML

Abstract

Structure-activity studies on a hexapeptide N-terminal cleavage product of a dodecamer substrate led to the identification of very potent and highly specific inhibitors of the HCV NS3 protease/NS4A cofactor peptide complex. The largest increase in potency was accomplished by the introduction of a (4R)-naphthalen-1-yl-4-methoxy substituent to the P2 proline. N-Terminal truncation resulted in tetrapeptides containing a C-terminal carboxylic acid, which exhibited low micromolar activity against the HCV serine protease.