Novel 2-oxoimidazolidine-4-carboxylic acid derivatives as hepatitis C virus NS3-4A serine protease inhibitors: synthesis, activity, and X-ray crystal structure of an enzyme inhibitor complex.
Synthesis and HCV NS3 serine protease inhibitory activity of some novel 2-oxoimidazolidine-4-carboxylic acid derivatives are reported. Inhibitors derived from this new P2 core exhibited activity in the low microM range. X-ray structure of an inhibitor, 15c bound to the protease is presented.
Arasappan
Ashok
A
Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. ashok.arasappan@spcorp.com
Njoroge
F George
FG
Parekh
Tejal N
TN
Yang
Xiaozheng
X
Pichardo
John
J
Butkiewicz
Nancy
N
Prongay
Andrew
A
Yao
Nanhua
N
Girijavallabhan
Viyyoor
V
D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D018360:Crystallography, X-Ray / Q000379:methods*; D016174:Hepacivirus / Q000187:drug effects / Q000201:enzymology*; D048289:Imidazolidines / Q000138:chemical synthesis* / Q000494:pharmacology; D011487:Protein Conformation; D012697:Serine Endopeptidases / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D002264:Carboxylic Acids; D048289:Imidazolidines; 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