Phenethyl amides as novel noncovalent inhibitors of hepatitis C virus NS3/4A protease: discovery, initial SAR, and molecular modeling.
The discovery of novel, reversible and competitive tripeptide inhibitors of the Hepatitis C virus NS3/4A serine protease is described. These inhibitors are characterized by the presence of a C-terminal phenethyl amide group, which extends into the prime side of the enzyme. Initial SAR together with molecular modeling and data from site-directed mutagenesis suggest an interaction of the phenethyl amide group with Lys-136.
Colarusso
Stefania
S
Department of Chemistry, IRBM--MRL Rome, Via Pontina Km 30.600, 00040 Pomezia, Italy.
Koch
Uwe
U
Gerlach
Benjamin
B
Steinkühler
Christian
C
De Francesco
Raffaele
R
Altamura
Sergio
S
Matassa
Victor G
VG
Narjes
Frank
F
D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry; D001555:Benzene Derivatives / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D000577:Amides; D001555:Benzene Derivatives; 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