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.
Perni
Robert B
RB
Vertex Pharmaceuticals Inc., 130 Waverly Street, Cambridge, MA 02139, USA. robert_perni@vrtx.com
Britt
Shawn D
SD
Court
John C
JC
Courtney
Lawrence F
LF
Deininger
David D
DD
Farmer
Luc J
LJ
Gates
Cynthia A
CA
Harbeson
Scott L
SL
Kim
Joseph L
JL
Landro
James A
JA
Levin
Rhonda B
RB
Luong
Yu-Ping
YP
O'Malley
Ethan T
ET
Pitlik
Janos
J
Rao
B Govinda
BG
Schairer
Wayne C
WC
Thomson
John A
JA
Tung
Roger D
RD
Van Drie
John H
JH
Wei
Yunyi
Y
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