Derivatives of imidazotriazine and pyrrolotriazine C-nucleosides as potential new anti-HCV agents
| Autor: | Richard Hufton, Jianmin Duan, Carlie T. Gannon, Tyrone Pieter Jeynes, Barbara Frey, George Kukolj, Alistair George Draffan, Rosliana Halim, Van T. T. Nguyen, Benjamin H. Fraser, Bruno Simoneau, Melinda J. Pryor, Edward M. Tyndall, Lilly Michael John, Kate Porter, Michael Harding, Silas Bond, Julia Cianci, Brett Pool, Simon P. Tucker, Bo Lin, Danielle Tilmanis, Angela Luttick, Saba Jahangiri, Veronika Wirth, Richard Bethell, Craig J. Morton |
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| Rok vydání: | 2014 |
| Předmět: |
Carcinoma
Hepatocellular Stereochemistry Clinical Biochemistry Pharmaceutical Science Hepacivirus Virus Replication Biochemistry Antiviral Agents Ns5b polymerase Structure-Activity Relationship Drug Discovery medicine Tumor Cells Cultured Humans Pyrroles C nucleosides Cytotoxicity Molecular Biology Cell Proliferation Molecular Structure Chemistry Anti hiv Triazines Organic Chemistry Liver Neoplasms Imidazoles Nucleosides Adenosine Hepatitis C In vitro Molecular Medicine RNA Viral medicine.drug |
| Zdroj: | Bioorganicmedicinal chemistry letters. 24(21) |
| ISSN: | 1464-3405 |
| Popis: | Previous investigations identified 2′-C-Me-branched ribo-C-nucleoside adenosine analogues, 1, which contains a pyrrolo[2,1-f][1,2,4]triazin-4-amine heterocyclic base, and 2, which contains an imidazo[2,1-f][1,2,4]triazin-4-amine heterocyclic base as two compounds with promising anti-HCV in vitro activity. This Letter describes the synthesis and evaluation of a series of novel analogues of these compounds substituted at the 2-, 7-, and 8-positions of the heterocyclic bases. A number of active new HCV inhibitors were identified but most compounds also demonstrated unacceptable cytotoxicity. However, the 7-fluoro analogue of 1 displayed good potency with a promising cytotherapeutic margin. |
| Databáze: | OpenAIRE |
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