P2-P4 macrocyclic inhibitors of hepatitis C virus NS3-4A serine protease.
Synthesis and HCV NS3 serine protease inhibitory activity of 4-hydroxyproline derived macrocyclic inhibitors and SAR around this macrocyclic core is described in this communication. X-ray structure of inhibitor 38 bound to the protease is discussed.
Arasappan
Ashok
A
Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. ashok.arasappan@spcorp.com
Njoroge
F George
FG
Chen
Kevin X
KX
Venkatraman
Srikanth
S
Parekh
Tejal N
TN
Gu
Haining
H
Pichardo
John
J
Butkiewicz
Nancy
N
Prongay
Andrew
A
Madison
Vincent
V
Girijavallabhan
Viyyoor
V
D006526:Hepatitis C / Q000201:enzymology*; D047028:Macrocyclic Compounds / Q000494:pharmacology*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D014961:X-Ray Diffraction; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D047028:Macrocyclic Compounds; D015842:Serine Proteinase Inhibitors; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases