Inhibitors of hepatitis C virus NS3.4A protease 2. Warhead SAR and optimization.
The alpha-ketoamide warhead (e.g., 15) was found to be a practical replacement for aliphatic aldehydes in a series of HCV NS3.4A protease inhibitors. Structure-activity relationships and prime side optimization are discussed.
Vertex Pharmaceuticals Inc., 130 Waverly Street, Cambridge, MA 02139, USA.
Robert B
RB
Perni
Janos
J
Pitlik
Shawn D
SD
Britt
John J
JJ
Court
Lawrence F
LF
Courtney
David D
DD
Deininger
Luc J
LJ
Farmer
Cynthia A
CA
Gates
Scott L
SL
Harbeson
Rhonda B
RB
Levin
Chao
C
Lin
Kai
K
Lin
Young-Choon
YC
Moon
Yu-Ping
YP
Luong
Ethan T
ET
O'Malley
B Govinda
BG
Rao
John A
JA
Thomson
Roger D
RD
Tung
John H
JH
Van Drie
Yunyi
Y
Wei
D002219:Carbamates / Q000737:chemistry / Q000378:metabolism; D016174:Hepacivirus / Q000187:drug effects / Q000201:enzymology*; D047028:Macrocyclic Compounds; D011804:Quinolines; D012697:Serine Endopeptidases / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry / Q000378:metabolism; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D002219:Carbamates; D047028:Macrocyclic Compounds; D011804:Quinolines; D012697:Serine Endopeptidases; D015842:Serine Proteinase Inhibitors; D013844:Thiazoles; D017361:Viral Nonstructural Proteins; C479555:BILN 2061; C084422:NS3 protein, hepatitis C virus; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C093542:NS4 protein, hepatitis C virus