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Potent inhibitors of HCV-NS3 protease derived from boronic acids.

Abstract：

:Chronic hepatitis C infection is the leading causes for cirrhosis of the liver and hepatocellular carcinoma, leading to liver failure and liver transplantation. The etiological agent, HCV virus produces a single positive strand of RNA that is processed with the help of serine protease NS3 to produce mature virus. Inhibition of NS3 protease can be potentially used to develop effective drugs for HCV infections. Numerous efforts are now underway to develop potent inhibitors of HCV protease that contain ketoamides as serine traps. Herein we report the synthesis of a series of potent inhibitors that contain a boronic acid as a serine trap. The activity of these compounds were optimized to 200pM. X-ray structure of compound 17 bound to NS3 protease is also discussed.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Venkatraman S,Wu W,Prongay A,Girijavallabhan V,George Njoroge F

doi

10.1016/j.bmcl.2008.10.124

subject

Has Abstract

pub_date

2009-01-01 00:00:00

pages

180-3

issue

1

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(08)01340-1

journal_volume

19

pub_type

杂志文章

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