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

Autor:	Van-Duc Le, Philip J. Dudfield, Charles W. Rees, Stephen David Lindell
Rok vydání:	1999
Předmět:	chemistry.chemical_classification biology Chemistry Stereochemistry AMP deaminase Riboside Hydrazide Adenosine chemistry.chemical_compound Adenosine deaminase biology.protein medicine Nucleotide Phosphorus trichloride Triazine medicine.drug
Zdroj:	Journal of the Chemical Society, Perkin Transactions 1. :2937-2942
ISSN:	1364-5463 0300-922X
DOI:	10.1039/a905177e
Popis:	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][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).
Databáze:	OpenAIRE
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