Discovery of Proline Sulfonamides as Potent and Selective Hepatitis C Virus NS5b Polymerase Inhibitors. Evidence for a New NS5b Polymerase Binding Site

Autor:	John O'Connell, Kevin J. Curran, Kristine Svenson, Anita Y. M. Howe, Kitae Lim, Steven F. Sukits, Mengxiao Shi, Ariamala Gopalsamy, Boris Feld, Girija Krishnamurthy, Rajiv Chopra, Tarek S. Mansour, Atul Agarwal, Mark Orlowski, Joel Bard, John W. Ellingboe, Gregory Ciszewski
Rok vydání:	2006
Předmět:	Models Molecular Proline Hepatitis C virus Molecular Conformation Viral Nonstructural Proteins Crystallography X-Ray medicine.disease_cause Antiviral Agents Structure-Activity Relationship chemistry.chemical_compound Drug Discovery medicine Transferase Binding site NS5B chemistry.chemical_classification Sulfonamides Binding Sites biology virus diseases Active site Molecular biology digestive system diseases Enzyme chemistry Biochemistry Enzyme inhibitor RNA Polymerase Inhibitor biology.protein Molecular Medicine
Zdroj:	Journal of Medicinal Chemistry. 49:3052-3055
ISSN:	1520-4804 0022-2623
Popis:	Through high throughput screening, substituted proline sulfonamide 6 was identified as HCV NS5b RNA-dependent RNA polymerase inhibitor. Optimization of various regions of the lead molecule resulted in compounds that displayed good potency and selectivity. The crystal structure of 6 and NS5b polymerase complex confirmed the binding near the active site region. The optimization approach and SAR are discussed in detail.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b5dd28614e63376f9b254693c90ad648 https://doi.org/10.1021/jm060168g Zobrazit plný text záznamu