160593-86-2Relevant academic research and scientific papers
Synthesis and biological activity of 4-amino-1-(β-D- ribofuranosyl)imidazo[4,5-d]pyridazin-7-one
Berry,Wotring,Drach,Townsend
, p. 2001 - 2011 (1994)
The Lewis acid catalyzed ribosylation of 5(4)-cyano-4(5)-(5-methyl-1,2,4- oxadiazol-3-yl)-1H-imidazole (2) with 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D- ribose gave only 4-(5-methyl-1,2,4-oxadiazol-3-yl)-1-(2,3,5-tri-O-benzoyl- β-D-ribofuranosyl)imidazole-5-carbonitrile (3). Treatment of 3 with methanolic ammonia gave 4-(5-methyl-1,2,4-oxadiazol-3-yl)-1-(β-D- ribofuranosyl)imidazole-5-carbonitrile (4). Treatment of 4 with hydrogen peroxide in ammonia gave 4-(5-methyl-1,2,4-oxadiazol-3-yl)-1 (β-D- ribofuranosyl)imidazole-5-carboxamide (5). When 5 was treated with sodium hydride in dimethyl-sulfoxide a rearrangement (mononuclear heterocyclic rearrangement, m.h.r.) occurred to give a modest 17% yield of 4-acetamido-1- (β-D-ribofuranosyl)imidazo[4,5-d]pyridazin-7-one (6). Treatment of 6 with aqueous ammonia gave 4-amino-1-(β-D-ribofuranosyl)imidazo[4,5-d]pyridazin- 7-one (1). The synthesis of compound 1 using the m.h.r. for the preparation of a single regioisomer of the imidazo[4,5-d]pyridazin-7-one ring system, has demonstrated the potential of this methodology. Neither compound 5 nor 6 affected the growth or replication of human foreskin fibroblasts (HFF cells) or human cytomegalovirus (HCMV). In contrast, compound I inhibited the replication of HCMV (IC50=29 μM) but produced visual cytotoxicity in uninfected HFF cells (IC50=70μM). Compound I also inhibited the proliferation of L1210 murine leukemic cells (IC50=25 μM), whereas the precursors 4 and 6 did not.
