Inhibitors of hepatitis C virus NS3.4A protease 1. Non-charged tetrapeptide variants.
Tetrapeptide-based peptidomimetic compounds have been shown to effectively inhibit the hepatitis C virus NS3.4A protease without the need of a charged functionality. An aldehyde is used as a prototype reversible electrophilic warhead. The SAR of the P1 and P2 inhibitor positions is discussed.
Vertex Pharmaceuticals Inc., 130 Waverly Street, Cambridge, MA 02139, USA. robert_perni@vrtx.com
Robert B
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Perni
Shawn D
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Britt
John C
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Court
Lawrence F
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Courtney
David D
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Deininger
Luc J
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Farmer
Cynthia A
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Gates
Scott L
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Harbeson
Joseph L
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Kim
James A
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Landro
Rhonda B
RB
Levin
Yu-Ping
YP
Luong
Ethan T
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O'Malley
Janos
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Pitlik
B Govinda
BG
Rao
Wayne C
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Schairer
John A
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Thomson
Roger D
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Tung
John H
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Van Drie
Yunyi
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Wei
D016174:Hepacivirus / Q000187:drug effects / Q000201:enzymology*; D007700:Kinetics; D008958:Models, Molecular; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D014961:X-Ray Diffraction
D009842:Oligopeptides; D011480:Protease Inhibitors