Derivatives of imidazotriazine and pyrrolotriazine C-nucleosides as potential new anti-HCV agents

Abstract 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.