Discovery of a novel bicycloproline P2 bearing peptidyl alpha-ketoamide LY514962 as HCV protease inhibitor.
We describe herein the design, syntheses and evaluation of a number of bicycloproline P2 bearing HCV protease inhibitors endowed with impressive enzyme potency, enzyme selectivity, cellular activity and favorable ADME profiles.
Yip
Yvonne
Y
Lilly Research Laboratory, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Victor
Frantz
F
Lamar
Jason
J
Johnson
Robert
R
Wang
Q May
QM
Barket
Donna
D
Glass
John
J
Jin
Ling
L
Liu
Lifei
L
Venable
Daryl
D
Wakulchik
Mark
M
Xie
Congping
C
Heinz
Beverly
B
Villarreal
Elcira
E
Colacino
Joe
J
Yumibe
Nathan
N
Tebbe
Mark
M
Munroe
John
J
Chen
Shu-Hui
SH
D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D004151:Dipeptides / Q000138:chemical synthesis / Q000494:pharmacology; D016174:Hepacivirus / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D008297:Male; D011392:Proline / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012697:Serine Endopeptidases / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D017361:Viral Nonstructural Proteins / Q000378:metabolism*; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D001643:Bridged Bicyclo Compounds; D004151:Dipeptides; D011392:Proline; 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