Jump to main content
Jump to site search

Issue 15, 2016
Previous Article Next Article

The synthesis of a series of adenosine A3 receptor agonists

Author affiliations

Abstract

A series of 1′-(6-aminopurin-9-yl)-1′-deoxy-N-methyl-β-D-ribofuranuronamides that were characterised by 2-dialkylamino-7-methyloxazolo[4,5-b]pyridin-5-ylmethyl substituents on N6 of interest for screening as selective adenosine A3 receptor agonists, have been synthesised. This work involved the synthesis of 2-dialkylamino-5-aminomethyl-7-methyloxazolo[4,5-b]pyridines and analogues that were coupled with the known 1′-(6-chloropurin-9-yl)-1′-deoxy-N-methyl-β-D-ribofuranuronamide. The oxazolo[4,5-b]pyridines were synthesized by regioselective functionalisation of 2,4-dimethylpyridine N-oxides. The regioselectivities of these reactions were found to depend upon the nature of the heterocycle with 2-dimethylamino-5,7-dimethyloxazolo[4,5-b]pyridine-N-oxide undergoing regioselective functionalisation at the 7-methyl group on reaction with trifluoroacetic anhydride in contrast to the reaction of 4,6-dimethyl-3-hydroxypyridine-N-oxide with acetic anhydride that resulted in functionalisation of the 6-methyl group. To optimise selectivity for the A3 receptor, 5-aminomethyl-7-bromo-2-dimethylamino-4-[(3-methylisoxazol-5-yl)methoxy]benzo[d]oxazole was synthesised and coupled with the 1′-(6-chloropurin-9-yl)-1′-deoxy-N-methyl-β-D-ribofuranuronamide. The products were active as selective adenosine A3 agonists.

Graphical abstract: The synthesis of a series of adenosine A3 receptor agonists

Back to tab navigation

Supplementary files

Article information


Submitted
29 Jan 2016
Accepted
09 Mar 2016
First published
14 Mar 2016

Org. Biomol. Chem., 2016,14, 3765-3781
Article type
Paper

The synthesis of a series of adenosine A3 receptor agonists

K. J. Broadley, E. Burnell, R. H. Davies, A. T. L. Lee, S. Snee and E. J. Thomas, Org. Biomol. Chem., 2016, 14, 3765
DOI: 10.1039/C6OB00244G

Social activity

Search articles by author

Spotlight

Advertisements