Back to Search
Start Over
The synthesis of a series of adenosine A3 receptor agonists.
- Source :
-
Organic & biomolecular chemistry [Org Biomol Chem] 2016 Apr 12; Vol. 14 (15), pp. 3765-81. - Publication Year :
- 2016
-
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.
- Subjects :
- Adenosine analogs & derivatives
Adenosine chemical synthesis
Adenosine pharmacology
Adenosine A3 Receptor Agonists chemistry
Crystallography, X-Ray
Humans
Models, Molecular
Oxazoles chemical synthesis
Oxazoles chemistry
Oxazoles pharmacology
Pyridines chemical synthesis
Pyridines chemistry
Pyridines pharmacology
Adenosine A3 Receptor Agonists chemical synthesis
Adenosine A3 Receptor Agonists pharmacology
Receptor, Adenosine A3 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1477-0539
- Volume :
- 14
- Issue :
- 15
- Database :
- MEDLINE
- Journal :
- Organic & biomolecular chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 27001924
- Full Text :
- https://doi.org/10.1039/c6ob00244g