title: Discovery of Narlaprevir (SCH 900518): A Potent, Second Generation HCV NS3 Serine Protease Inhibitor.
abstract: 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 (∼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.
authors.affiliation: Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: Ashok
authors.initials: A
authors.lastname: Arasappan
authors.affiliation: Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: Frank
authors.initials: F
authors.lastname: Bennett
authors.affiliation: Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: Stephane L
authors.initials: SL
authors.lastname: Bogen
authors.affiliation: Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: Srikanth
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authors.lastname: Venkatraman
authors.affiliation: Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: Melissa
authors.initials: M
authors.lastname: Blackman
authors.affiliation: Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: Kevin X
authors.initials: KX
authors.lastname: Chen
authors.affiliation: Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: Siska
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authors.lastname: Hendrata
authors.affiliation: Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: Regina M
authors.initials: RM
authors.lastname: Huelgas
authors.affiliation: Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: Latha
authors.initials: L
authors.lastname: Nair
authors.affiliation: Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: Angela I
authors.initials: AI
authors.lastname: Padilla
authors.affiliation: Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: Weidong
authors.initials: W
authors.lastname: Pan
authors.affiliation: Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: Russell
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authors.lastname: Pike
authors.affiliation: Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: Patrick
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authors.lastname: Pinto
authors.affiliation: Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: Sumei
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authors.lastname: Ruan
authors.affiliation: Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: Mousumi
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authors.lastname: Sannigrahi
authors.affiliation: Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: Francisco
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authors.lastname: Velazquez
authors.affiliation: Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: Bancha
authors.initials: B
authors.lastname: Vibulbhan
authors.affiliation: Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: Wanli
authors.initials: W
authors.lastname: Wu
authors.affiliation: Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: Weiying
authors.initials: W
authors.lastname: Yang
authors.affiliation: Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
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authors.initials: AK
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authors.affiliation: Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
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authors.initials: V
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authors.affiliation: Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: Neng-Yang
authors.initials: NY
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authors.affiliation: Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: Jianshe
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authors.affiliation: Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: Tao
authors.initials: T
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authors.affiliation: Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: Yan
authors.initials: Y
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authors.affiliation: Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: Jesse
authors.initials: J
authors.lastname: Wong
authors.affiliation: Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: Paul
authors.initials: P
authors.lastname: McNamara
authors.affiliation: Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: Andrew
authors.initials: A
authors.lastname: Prongay
authors.affiliation: Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: Vincent
authors.initials: V
authors.lastname: Madison
authors.affiliation: Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: John J
authors.initials: JJ
authors.lastname: Piwinski
authors.affiliation: Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: Kuo-Chi
authors.initials: KC
authors.lastname: Cheng
authors.affiliation: Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: Richard
authors.initials: R
authors.lastname: Morrison
authors.affiliation: Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: Bruce
authors.initials: B
authors.lastname: Malcolm
authors.affiliation: Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: Xiao
authors.initials: X
authors.lastname: Tong
authors.affiliation: Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: Robert
authors.initials: R
authors.lastname: Ralston
authors.affiliation: Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: F George
authors.initials: FG
authors.lastname: Njoroge
keywords: Hepatitis C virus NS3 serine protease inhibitor; SCH 900518; narlaprevir; α-ketoamide