SAR and pharmacokinetic studies on phenethylamide inhibitors of the hepatitis C virus NS3/NS4A serine protease.
SAR on the phenethylamide 1 (Ki 1.2 microM) in the P2- and the P'-position led to potent inhibitors, one of which showed good exposure and low clearance when administered intramuscularly to rat.
Malancona
Savina
S
Department of Chemistry, Istituto di Ricerche di Biologia Molecolare, Merck Research Laboratories, Via Pontina Km 30.600, 00040 Pomezia, Rome, Italy.
Colarusso
Stefania
S
Ontoria
Jesus M
JM
Marchetti
Antonella
A
Poma
Marco
M
Stansfield
Ian
I
Laufer
Ralph
R
Di Marco
Annalise
A
Taliani
Marina
M
Verdirame
Maria
M
Gonzalez-Paz
Odalys
O
Matassa
Victor G
VG
Narjes
Frank
F
D000818:Animals; D016174:Hepacivirus / Q000187:drug effects / Q000201:enzymology*; D010627:Phenethylamines / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D012697:Serine Endopeptidases / Q000493:pharmacokinetics*; D015842:Serine Proteinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000493:pharmacokinetics*; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D010627:Phenethylamines; D012697:Serine Endopeptidases; D015842:Serine Proteinase Inhibitors; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C093542:NS4 protein, hepatitis C virus