Browsing by Author "Hufton, R"

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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.