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

• Published in: Bioorganic & medicinal chemistry letters 2004-12, Vol.14 (23), p.5751-5755
• Main Authors: Arasappan, Ashok, Njoroge, F. George, Parekh, Tejal N., Yang, Xiaozheng, Pichardo, John, Butkiewicz, Nancy, Prongay, Andrew, Yao, Nanhua, Girijavallabhan, Viyyoor
• Format: Article
• Language: English
• Subjects: Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Biological and medical sciences; Carboxylic Acids - chemical synthesis; Carboxylic Acids - pharmacology; CRYSTAL STRUCTURE; Crystallography, X-Ray - methods; ENZYME INHIBITORS; Hepacivirus - drug effects; Hepacivirus - enzymology; HEPATITIS; Imidazolidines - chemical synthesis; Imidazolidines - pharmacology; MATERIALS SCIENCE; Medical sciences; Pharmacology. Drug treatments; Protein Conformation; SERINE; Serine Endopeptidases - metabolism; Serine Proteinase Inhibitors - chemical synthesis; Serine Proteinase Inhibitors - pharmacology; SYNTHESIS; Viral Nonstructural Proteins - antagonists & inhibitors
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2004.09.058

Synthesis and HCV NS3 serine protease inhibitory activity of some novel 2-oxoimidazolidine-4-carboxylic acid derivatives are reported. X-ray structure of an inhibitor, 15c bound to the protease is presented. 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 μM range. X-ray structure of an inhibitor, 15c bound to the protease is presented.