Hepatitis C virus NS3-4A serine protease inhibitors: use of a P2-P1 cyclopropyl alanine combination for improved potency.
Modification of the P(2) and P(1) side chains of earlier P(3)-capped alpha-ketoamide inhibitor of HCV NS3 serine protease 1 resulted in the discovery of compound 24 with about 10-fold improvement in potency.
Bogen
S
S
Chemical Research, Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. stephane.bogen@spcorp.com
Saksena
A K
AK
Arasappan
A
A
Gu
H
H
Njoroge
F G
FG
Girijavallabhan
V
V
Pichardo
J
J
Butkiewicz
N
N
Prongay
A
A
Madison
V
V
D000409:Alanine / Q000737:chemistry*; D015842:Serine Proteinase Inhibitors / Q000737:chemistry* / 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
D000409:Alanine; 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