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

Ashok Arasappan; F George Njoroge; Tejal N Parekh; Xiaozheng Yang; John Pichardo; Nancy Butkiewicz; Andrew Prongay; Nanhua Yao; Viyyoor Girijavallabhan

doi:10.1016/j.bmcl.2004.09.058

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

Bioorg Med Chem Lett. 2004 Dec 6;14(23):5751-5. doi: 10.1016/j.bmcl.2004.09.058.

Authors

Ashok Arasappan¹, F George Njoroge, Tejal N Parekh, Xiaozheng Yang, John Pichardo, Nancy Butkiewicz, Andrew Prongay, Nanhua Yao, Viyyoor Girijavallabhan

Affiliation

¹ Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. [email protected]

PMID: 15501035
DOI: 10.1016/j.bmcl.2004.09.058

Abstract

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.

MeSH terms

Carboxylic Acids / chemical synthesis*
Carboxylic Acids / pharmacology
Crystallography, X-Ray / methods*
Hepacivirus / drug effects
Hepacivirus / enzymology*
Imidazolidines / chemical synthesis*
Imidazolidines / pharmacology
Protein Conformation
Serine Endopeptidases / metabolism*
Serine Proteinase Inhibitors / chemical synthesis*
Serine Proteinase Inhibitors / pharmacology
Viral Nonstructural Proteins / antagonists & inhibitors*

Substances

Carboxylic Acids
Imidazolidines
NS3 protein, hepatitis C virus
Serine Proteinase Inhibitors
Viral Nonstructural Proteins
Serine Endopeptidases