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Evaluation of 2‐benzylidene‐1‐tetralone derivatives as antagonists of A 1 and A 2A adenosine receptors
Author(s) -
Legoabe Lesetja J.,
Walt Mietha M.,
Terre'Blanche Gisella
Publication year - 2018
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.13074
Subject(s) - adenosine , chemistry , adenosine receptor , stereochemistry , receptor , pharmacology , biochemistry , biology , agonist
Antagonists of the adenosine receptors (A 1 and A 2A ) are thought to be beneficial in neurological disorders, such as Alzheimer's and Parkinson's disease. The aim of this study was to explore 2‐benzylidene‐1‐tetralone derivatives as antagonists of A 1 and/or A 2A adenosine receptors. In general, the test compounds were found to be selective for the A 1 adenosine receptor, with only three test compounds possessing affinity for both the A 1 and A 2A adenosine receptor. The 2‐benzylidene‐1‐tetralones bearing a hydroxyl substituent at either position C5, C6 or C7 of ring A displayed favourable adenosine A 1 receptor binding, while C5 hydroxy substitution led to favourable A 2A adenosine receptor affinity. Interestingly, para ‐hydroxy substitution on ring B in combination with ring A bearing a hydroxy at position C6 or C7 provided the 2‐benzylidene‐1‐tetralones with both A 1 and A 2A adenosine receptor affinity. Compounds 4 and 8 displayed the highest A 1 and A 2A adenosine receptor affinity with values below 7 μ m . Both these compounds behaved as A 1 adenosine receptor antagonists in the performed GTP shift assays. In conclusion, the 2‐benzylidene‐1‐tetralone derivatives can be considered as lead compounds to design a new class of dual acting adenosine A 1 /A 2A receptor antagonists that may have potential in treating both dementia and locomotor deficits in Parkinson's disease.