Browsing by Author "Draffan, AG"

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    Derivatives of imidazotriazine and pyrrolotriazine C-nucleosides as potential new anti-HCV agents
    (Elsevier B.V., 2014-11-01) Draffan, AG; Frey, B; Fraser, BH; Pool, B; Gannon, C; Tyndall, EM; Cianci, J; Harding, M; Lilly, M; Hufton, R; Halim, R; Jahangiri, S; Bond, S; Jeynes, TP; Nguyen, VTT; Wirth, V; Luttick, A; Tilmanis, D; Pryor, M; Porter, K; Morton, CJ; Lin, B; Duan, J; Bethell, RC; Kukojl, G; Simoneau, B; Tucker, SP
    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. © 2014 Elsevier Ltd.
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    Synthesis of 1,4-triazole linked zanamivir dimers as highly potent inhibitors of influenza A and B
    (The Royal Society of Chemistry, 2012-11-29) Fraser, BH; Hamilton, S; Krause-Heuer, AM; Wright, PJ; Greguric, I; Tucker, SP; Draffan, AG; Fokin, VV; Sharpless, KB
    The copper catalyzed azide alkyne cycloaddition (CuAAC) reaction – the quintessential ‘click’ reaction – was used to synthesise dimers of the neuraminidase inhibitor zanamivir in high yields. The effect upon anti-viral activity of varying the linker length and the number of triazole units was explored. All dimers were tested for anti-viral activity against influenza A/Sydney/5/97 and B/Harbin/7/94 in a cytopathic effect (CPE) assay. © Royal Society of Chemistry