Non-nucleoside inhibitors of HCV NS5B polymerase. Part 1: Synthetic and computational exploration of the binding modes of benzothiadiazine and 1,4-benzothiazine HCV NS5b polymerase inhibitors

Autor:	Stacey Renee Spencer, Vincent Leveque, Fell Jay Bradford, John A. Josey, Stengel Peter J, John P. Fischer, Robert Than Hendricks, April L. Bernacki, James F. Blake, Sophie Le Pogam, Sonal Rajyaguru, Steven Swallow, Robinson John E, Isabel Najera, Harris Jason R
Rok vydání:	2009
Předmět:	Stereochemistry Clinical Biochemistry Thiazines Pharmaceutical Science Hepacivirus Viral Nonstructural Proteins Benzothiazine Benzothiadiazines Crystallography X-Ray Virus Replication Antiviral Agents Biochemistry Structure-Activity Relationship chemistry.chemical_compound Drug Discovery Humans Computer Simulation Enzyme Inhibitors Molecular Biology NS5B Polymerase chemistry.chemical_classification biology Chemistry Organic Chemistry Computational Biology virus diseases DNA-Directed RNA Polymerases Nucleotidyltransferase digestive system diseases Enzyme Enzyme inhibitor Benzothiadiazine biology.protein Molecular Medicine Nucleoside Protein Binding
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 19:3637-3641
ISSN:	0960-894X
Popis:	The importance of internal hydrogen bonding in a series of benzothiadiazine and 1,4-benzothiazine NS5b inhibitors has been explored. Computational analysis has been used to compare the protonated vs. anionic forms of each series and we demonstrate that activity against HCV NS5b polymerase is best explained using the anionic forms. The syntheses and structure-activity relationships for a variety of new analogs are also discussed.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::275a5fed7b4e0f2c32fc43549f46ac01 https://doi.org/10.1016/j.bmcl.2009.04.119 Zobrazit plný text záznamu Full Text from ScienceDirect