The synthesis of a series of adenosine A3 receptor agonists

Broadley, Kenneth John ORCID: https://orcid.org/0000-0002-3339-2050, Burnell, Erica, Davies, Robin H., Lee, Alan T. L., Snee, Stephen and Thomas, Eric J. 2016. The synthesis of a series of adenosine A3 receptor agonists. Organic & Biomolecular Chemistry 14 (15) , pp. 3765-3781. 10.1039/C6OB00244G

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Pharmacy
Additional Information:	PDF uploaded in accordance with publisher's policies at http://www.sherpa.ac.uk/romeo/issn/1477-0520/ (accessed 9.6.16).
Publisher:	Royal Society of Chemistry
ISSN:	1477-0520
Date of First Compliant Deposit:	9 June 2016
Date of Acceptance:	9 March 2016
Last Modified:	07 Nov 2023 00:14
URI:	https://orca.cardiff.ac.uk/id/eprint/91685

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