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Structure-activity study on a novel series of macrocyclic inhibitors of the hepatitis C virus NS3 protease leading to the discovery of BILN 2061.

Abstract：

:From the discovery of competitive hexapeptide inhibitors, potent and selective HCV NS3 protease macrocyclic inhibitors have been identified. Structure-activity relationship studies were performed focusing on optimizing the N-terminal carbamate and the aromatic substituent on the (4R)-hydroxyproline moiety. Inhibitors meeting the potency criteria in the cell-based assay and with improved oral bioavailability in rats were identified. BILN 2061 was selected as the best compound, the first NS3 protease inhibitor reported with antiviral activity in man.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Llinàs-Brunet M,Bailey MD,Bolger G,Brochu C,Faucher AM,Ferland JM,Garneau M,Ghiro E,Gorys V,Grand-Maître C,Halmos T,Lapeyre-Paquette N,Liard F,Poirier M,Rhéaume M,Tsantrizos YS,Lamarre D

doi

10.1021/jm0342414

keywords:

subject

Has Abstract

pub_date

2004-03-25 00:00:00

pages

1605-8

issue

7

eissn

0022-2623

issn

1520-4804

journal_volume

47

pub_type

杂志文章

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