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Title: 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 200 pM. X-ray structure of compound 17 bound to NS3 protease is also discussed.

Authors:
; ; ; ;
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1005725
Resource Type:
Journal Article
Journal Name:
Bioorg. Med. Chem. Lett.
Additional Journal Information:
Journal Volume: 19; Journal Issue: (1) ; 01, 2009; Journal ID: ISSN 0960-894X
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; 99 GENERAL AND MISCELLANEOUS//MATHEMATICS, COMPUTING, AND INFORMATION SCIENCE; BORONIC ACIDS; HEPATITIS; LIVER; RNA; SERINE; SYNTHESIS

Citation Formats

Venkatraman, Srikanth, Wu, Wanli, Prongay, Andrew, Girijavallabhan, Viyyoor, Njoroge, F George, and SPRI). Potent inhibitors of HCV-NS3 protease derived from boronic acids. United States: N. p., 2009. Web. doi:10.1016/j.bmcl.2008.10.124.
Venkatraman, Srikanth, Wu, Wanli, Prongay, Andrew, Girijavallabhan, Viyyoor, Njoroge, F George, & SPRI). Potent inhibitors of HCV-NS3 protease derived from boronic acids. United States. https://doi.org/10.1016/j.bmcl.2008.10.124
Venkatraman, Srikanth, Wu, Wanli, Prongay, Andrew, Girijavallabhan, Viyyoor, Njoroge, F George, and SPRI). 2009. "Potent inhibitors of HCV-NS3 protease derived from boronic acids". United States. https://doi.org/10.1016/j.bmcl.2008.10.124.
@article{osti_1005725,
title = {Potent inhibitors of HCV-NS3 protease derived from boronic acids},
author = {Venkatraman, Srikanth and Wu, Wanli and Prongay, Andrew and Girijavallabhan, Viyyoor and Njoroge, F George and SPRI)},
abstractNote = {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 200 pM. X-ray structure of compound 17 bound to NS3 protease is also discussed.},
doi = {10.1016/j.bmcl.2008.10.124},
url = {https://www.osti.gov/biblio/1005725}, journal = {Bioorg. Med. Chem. Lett.},
issn = {0960-894X},
number = (1) ; 01, 2009,
volume = 19,
place = {United States},
year = {Thu Jul 23 00:00:00 EDT 2009},
month = {Thu Jul 23 00:00:00 EDT 2009}
}