367258-43-3Relevant academic research and scientific papers
Potent 7-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid-based macrocyclic inhibitors of hepatitis C virus NS3 protease
Chen, Kevin X.,Njoroge, F. George,Pichardo, John,Prongay, Andrew,Butkiewicz, Nancy,Yao, Nanhua,Madison, Vincent,Girijavallabhan, Viyyoor
, p. 567 - 574 (2007/10/03)
The NS3 protease of hepatitis C virus (HCV) has emerged as one of the best characterized targets for next-generation HCV therapy. The tetrapeptide 1 and pentapeptide 2 are α-ketoamide-type HCV serine protease inhibitors with modest potency. We envisioned
Novel potent hepatitis C virus NS3 serine protease inhibitors derived from proline-based macrocycles
Chen, Kevin X.,Njoroge, F. George,Arasappan, Ashok,Venkatraman, Srikanth,Vibulbhan, Bancha,Yang, Weiying,Parekh, Tejal N.,Pichardo, John,Prongay, Andrew,Cheng, Kuo-Chi,Butkiewicz, Nancy,Yao, Nanhua,Madison, Vincent,Girijavallabhan, Viyyoor
, p. 995 - 1005 (2007/10/03)
The hepatitis C virus (HCV) NS3 protease is essential for viral replication. It has been a target of choice for intensive drug discovery research. On the basis of an active pentapeptide inhibitor, 1, we envisioned that macrocyclization from the P2 proline
Discovery of (1R,5S)-N-[3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl]-3- [2(S)-[[[(1,1-dimethylethyl)amino]carbonyl]amino]-3,3-dimethyl-1-oxobutyl]-6, 6-dimethyl-3-azabicyclo[3.1.0]hexan-2(S)-carboxamide (SCH 503034), a selective, potent, orally bioavailable hepatitis C virus NS3 protease inhibitor: A potential therapeutic agent for the treatment of hepatitis C infection
Venkatraman, Srikanth,Bogen, Stéphane L.,Arasappan, Ashok,Bennett, Frank,Chen, Kevin,Jao, Edwin,Liu, Yi-Tsung,Lovey, Raymond,Hendrata, Siska,Huang, Yuhua,Pan, Weidong,Parekh, Tejal,Pinto, Patrick,Popov, Veljko,Pike, Russel,Ruan, Sumei,Santhanam, Bama,Vibulbhan, Bancha,Wu, Wanli,Yang, Weiying,Kong, Jianshe,Liang, Xiang,Wong, Jesse,Liu, Rong,Butkiewicz, Nancy,Chase, Robert,Hart, Andrea,Agrawal, Sony,Ingravallo, Paul,Pichardo, John,Kong, Rong,Baroudy, Bahige,Malcolm, Bruce,Guo, Zhuyan,Prongay, Andrew,Madison, Vincent,Broske, Lisa,Cui, Xiaoming,Cheng, Kuo-Chi,Hsieh, Yunsheng,Brisson, Jean-Marc,Prelusky, Danial,Korfmacher, Walter,White, Ronald,Bogdanowich-Knipp, Susan,Pavlovsky, Anastasia,Bradley, Prudence,Saksena, Anil K.,Ganguly, Ashit,Piwinski, John,Girijavallabhan, Viyyoor,Njoroge, F. George
, p. 6074 - 6086 (2007/10/03)
Hepatitis C virus (HCV) infection is the major cause of chronic liver disease, leading to cirrhosis and hepatocellular carcinoma, which affects more than 170 million people worldwide. Currently the only therapeutic regimens are subcutaneous interferon-α or polyethylene glycol (PEG)-interferon-α 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 about 40% of the patients showing sustained virological response. Herein, the SAR leading to the discovery of 70 (SCH 503034), a novel, potent, selective, orally bioavailable NS3 protease inhibitor that has been advanced to clinical trials in human beings for the treatment of hepatitis C viral infections is described. X-ray structure of inhibitor 70 complexed with the NS3 protease and biological data are also discussed.
Design and synthesis of depeptidized macrocyclic inhibitors of hepatitis C NS3-4A protease using structure-based drug design
Venkatraman, Srikanth,Njoroge, F. George,Girijavallabhan, Viyyoor M.,Madison, Vincent S.,Yao, Nanua H.,Prongay, Andrew J.,Butkiewicz, Nancy,Pichardo, John
, p. 5088 - 5091 (2007/10/03)
Hepatitus C virus (HCV) NS3, when bound to NS4A cofactor, facilitates development of mature virons by catalyzing cleavage of a polyprotein to form functional and structural proteins of HCV. The enzyme has a shallow binding pocket at the catalytic site, ma
Design, synthesis, and biological activity of m-tyrosine-based 16- and 17-membered macrocyclic inhibitors of hepatitis C virus NS3 serine protease
Chen, Kevin X.,Njoroge, F. George,Pichardo, John,Prongay, Andrew,Butkiewicz, Nancy,Yao, Nanhua,Madison, Vincent,Girijavallabhan, Viyyoor
, p. 6229 - 6235 (2007/10/03)
The limited efficacy and considerable side effects of currently available therapies for the treatment of hepatitis C virus (HCV) infection have prompted significant efforts toward the development of safe and effective new therapeutics. The pentapeptide α-
Proline-based macrocyclic inhibitors of the hepatitis C virus: Stereoselective synthesis and biological activity
Chen, Kevin X.,Njoroge, F. George,Vibulbhan, Bancha,Prongay, Andrew,Pichardo, John,Madison, Vincent,Buevich, Alexei,Chan, Tze-Ming
, p. 7024 - 7028 (2007/10/03)
Life-saving donut: Macrocyclization through a Mitsunobu reaction was used to synthesize a 17-membered macrocycle. The bicyclic acetal core was prepared completely diastereoselectively. The macrocyclic peptidomimetic surrogate of the P2-P3 dipeptide moiety was designed to function as a hepatitis C virus (HCV) NS3 serine protease inhibitor, and the pentapeptide α-ketoamides derived from the macrocycle were shown to be potent HCV inhibitors. (Figure Presented).
Synthesis and biological activity of macrocyclic inhibitors of hepatitis C virus (HCV) NS3 protease
Chen, Kevin X.,Njoroge, F. George,Prongay, Andrew,Pichardo, John,Madison, Vincent,Girijavallabhan, Viyyoor
, p. 4475 - 4478 (2007/10/03)
The 17-membered phenylalanine-based macrocycle 6 was prepared starting from 3-iodo-phenylalanine. Macrocyclization of alkene phenyl iodide 5 was effected through a palladium-catalyzed Heck reaction. The macrocyclic α-ketoamides were active inhibitors of t
