864824-57-7Relevant academic research and scientific papers
Toward second generation hepatitis C virus NS3 serine protease inhibitors: Discovery of novel P4 modified analogues with improved potency and pharmacokinetic profile
Arasappan, Ashok,Padilla, Angela I.,Jao, Edwin,Bennett, Frank,Bogen, Stephane L.,Chen, Kevin X.,Pike, Russell E.,Sannigrahi, Mousumi,Soares, Joana,Venkatraman, Srikanth,Vibulbhan, Bancha,Saksena, Anil K.,Girijavallabhan, Viyyoor,Tong, Xiao,Cheng, Kuo-Chi,Njoroge, F. George
scheme or table, p. 2806 - 2817 (2010/01/16)
Hepatitis C virus (HCV) infection is a global health crisis leading to liver cirrhosis, hepatocellular carcinoma, and liver failure in humans. Recently, we disclosed the discovery of Boceprevir, SCH 503034 (1), a novel, potent, selective, orally bioavaila
Discovery of novel P3 sulfonamide-capped inhibitors of HCV NS3 protease. Inhibitors with improved cellular potencies
Venkatraman, Srikanth,Blackman, Mellissa,Wu, Wanli,Nair, Latha,Arasappan, Ashok,Padilla, Angela,Bogen, Stéphane,Bennett, Frank,Chen, Kevin,Pichardo, John,Tong, Xiao,Prongay, Andrew,Cheng, Kuo-Chi,Girijavallabhan, Viyyoor,George Njoroge
experimental part, p. 4486 - 4495 (2009/10/10)
Hepatitis C Virus (HCV) infection is the major cause of chronic liver disease, leading to cirrhosis and hepatocellular carcinoma, which affects more than 200 million people worldwide. Currently the only therapeutic regimens are subcutaneous interferon-α or PEG-interferon alone or in combination with oral ribavirin. Although combination therapy is reasonably successful with the majority of genotypes, its efficacy against the predominant genotype (genotype 1) is moderate at best, with only ～50% of the patients showing sustained virological response. We recently disclosed the discovery of Boceprevir, SCH 503034 (1), which is a novel, potent, selective, orally bioavailable NS3 protease inhibitor that has been shown to be efficacious in humans and is currently undergoing clinical trials. As second generation compounds, we have further explored various novel structures with the aim of improving enzyme and cellular binding activities of 1. Herein, we disclose our efforts toward the identification of a novel P3 sulfonamide-capped inhibitor that demonstrated improved binding and cellular activity compared to 1. X-ray structure of one of these inhibitors bound to the enzyme revealed a hydrogen bond of the P3 sulfonamide group to Cys-159 which resulted in improved binding and cellular potency.
NOVEL COMPOUNDS AS INHIBITORS OF HEPATITIS C VIRUS NS3 SERINE PROTEASE
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Page/Page column 91, (2008/06/13)
The present invention discloses novel compounds which have HCV protease inhibitory activity as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such compounds as well as methods of using them to treat disorders associated with the HCV protease.
