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 Vol. 14; no. 23; pp. 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: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 06.12.2004; Elsevier
• 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; Imidazole derivatives; Serine endopeptidases; Enzyme; Inhibitor enzyme complex; Biological activity; Virus; Peptidases; Carboxylic acid; Hydrolases; Antiviral; Ureas; Flaviviridae; Chemical synthesis; Hepatitis C virus; Hepacivirus; Protease inhibitor; Crystalline structure
• 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.