Design, synthesis, and antiviral properties of 4'-substituted ribonucleosides as inhibitors of hepatitis C virus replication: the discovery of R1479

Autor:	I. Najera, Sophie Le Pogam, Graham Maile, Hobbs Christopher John, JH Merrett, Steven Swallow, Carl Laxton, Julie Hang, Rene Devos, Stewart J. Baker, Han Ma, Keshab Sarma, Julian Symons, Klaus Klumpp, David Bernard Smith, Vincent Leveque, David R. Vesey, Peter Blomgren, Mark D. Smith, Arkadius Pichota, Joseph Armstrong Martin, W.R. Jiang, Caroline Granycome, Nick Cammack
Rok vydání:	2006
Předmět:	Hepatitis C virus Chemistry Pharmaceutical Clinical Biochemistry Drug Evaluation Preclinical Molecular Conformation Pharmaceutical Science Cytidine Hepacivirus medicine.disease_cause Virus Replication Biochemistry Antiviral Agents Virus chemistry.chemical_compound Inhibitory Concentration 50 RNA polymerase Drug Discovery medicine Replicon Molecular Biology NS5B Uridine Organic Chemistry Nucleosides Ribonucleoside Virology chemistry Viral replication Models Chemical Drug Design Molecular Medicine RNA Ribonucleosides Nucleoside
Zdroj:	Bioorganicmedicinal chemistry letters. 17(9)
ISSN:	0960-894X
Popis:	A series of 4'-substituted ribonucleoside derivatives has been prepared and evaluated for inhibition of hepatitis C virus (HCV) RNA replication in cell culture. The most potent and non-cytotoxic derivative was compound 28 (4'-azidocytidine, R1479) with an IC(50) of 1.28 microM in the HCV replicon system. The triphosphate of compound 28 was prepared and shown to be an inhibitor of RNA synthesis mediated by NS5B (IC(50)=320 nM), the RNA polymerase encoded by HCV. Data on related analogues have been used to generate some preliminary requirements for activity within this series of nucleosides.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::75a5e8af068b7cffce86f83a0bd1b0c8 https://pubmed.ncbi.nlm.nih.gov/17317178 Zobrazit plný text záznamu Full Text from ScienceDirect