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DOI: 10.1039/A905177E (Paper) Reference Section for: J. Chem. Soc., Perkin Trans. 1, 1999, 2937-2942

Synthesis of C-ribosyl 1,2,4-triazolo[3,4-f[hair space][hair space]][1,2,4]triazines as inhibitors of adenosine and AMP deaminases

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Philip J. Dudfield, Van-Duc Le, Stephen D. Lindell and Charles W. Rees

Abstract

Modified C-nucleosides and nucleotides with an enhanced tendency to undergo covalent hydration are of interest as potential inhibitors of adenosine deaminase (ADA) and AMP deaminase, respectively. In a search for such compounds we have synthesized 6-dimethylamino-3-(β-D-ribofuranosyl)-1,2,4-triazolo[3,4-f[hair space][hair space]][1,2,4]triazine 4 in four steps (42% overall yield) from the readily available allonic acid 6 and the hydrazine 7. The hydrazide 16 derived from 6 and 7 (78%) is converted directly into the cyclised chloro compound 19 (62%) with phosphorus trichloride oxide, followed by dechlorination (96%) and deprotection (90%). Riboside 4 undergoes partial hydration in water to the covalent hydrate 22, and is a modest inhibitor of mammalian ADA (IC50 180 µM).

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