Capped dipeptide phenethylamide inhibitors of the HCV NS3 protease.
The N-terminal aminoacid of phenethylamide tripeptide inhibitors of the hepatitis C virus NS3 protease can be replaced with an alpha-hydroxy acid to obtain more 'drug like' inhibitors with low micromolar activity. The preferred S-configuration of the capping residue can be explained by molecular modeling studies.
Nizi
Emanuela
E
Department of Chemistry, IRBM, MRL Rome, Via Pontina Km 30,600, 00040 Pomezia, Rome, Italy.
Koch
Uwe
U
Ontoria
Jesus M
JM
Marchetti
Antonella
A
Narjes
Frank
F
Malancona
Savina
S
Matassa
Victor G
VG
Gardelli
Cristina
C
D000577:Amides / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D000577:Amides; D011480:Protease 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