Discovery of Narlaprevir (SCH 900518): A Potent, Second Generation HCV NS3 Serine Protease Inhibitor

被引：74

作者：

Arasappan, Ashok ^{[1
]}

Bennett, Frank ^{[1
]}

Bogen, Stephane L. ^{[1
]}

Venkatraman, Srikanth ^{[1
]}

Blackman, Melissa ^{[1
]}

Chen, Kevin X. ^{[1
]}

Hendrata, Siska ^{[1
]}

Huang, Yuhua ^{[1
]}

Huelgas, Regina M. ^{[1
]}

Nair, Latha ^{[1
]}

Padilla, Angela I. ^{[1
]}

Pan, Weidong ^{[1
]}

Pike, Russell ^{[1
]}

Pinto, Patrick ^{[1
]}

Ruan, Sumei ^{[1
]}

Sannigrahi, Mousumi ^{[1
]}

Velazquez, Francisco ^{[1
]}

Vibulbhan, Bancha ^{[1
]}

Wu, Wanli ^{[1
]}

Yang, Weiying ^{[1
]}

Saksena, Anil K. ^{[1
]}

Girijavallabhan, Viyyoor ^{[1
]}

Shih, Neng-Yang ^{[1
]}

Kong, Jianshe ^{[1
]}

Meng, Tao ^{[1
]}

Jin, Yan ^{[1
]}

Wong, Jesse ^{[1
]}

McNamara, Paul ^{[1
]}

Prongay, Andrew ^{[1
]}

Madison, Vincent ^{[1
]}

Piwinski, John J. ^{[1
]}

Cheng, Kuo-Chi ^{[1
]}

Morrison, Richard ^{[1
]}

Malcolm, Bruce ^{[1
]}

Tong, Xiao ^{[1
]}

Ralston, Robert ^{[1
]}

Njoroge, F. George ^{[1
]}

机构：

[1] Schering Plough Res Inst, Kenilworth, NJ 07033 USA

来源：

ACS MEDICINAL CHEMISTRY LETTERS | 2010年 / 1卷 / 02期

关键词：

Hepatitis C virus NS3 serine protease inhibitor; alpha-ketoamide; narlaprevir; SCH; 900518; REPLICATION; MECHANISM; VX-950; RNA;

D O I：

10.1021/ml9000276

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Boceprevir (SCH 503034), 1, a novel HCV NS3 serine protease inhibitor discovered in our laboratories, is currently undergoing phase III clinical trials. Detailed investigations toward a second generation protease inhibitor culminated in the discovery of narlaprevir (SCH 900518), 37, with improved potency (similar to 10-fold over 1), pharmacokinetic profile and physicochemical characteristics, currently in phase II human trials. Exploration of synthetic sequence for preparation of 37 resulted in a route that required no silica gel purification for the entire synthesis.

引用

页码：64 / 69

页数：6

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