Evaluation of 2-benzylidene-1-tetralone derivatives as antagonists of A and A adenosine receptors.

Antagonists of the adenosine receptors (A and A ) 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 and/or A adenosine receptors. In general, the test compounds were found to be selective for the A adenosine receptor, with only three test compounds possessing affinity for both the A and A 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 receptor binding, while C5 hydroxy substitution led to favourable A 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 and A adenosine receptor affinity. Compounds 4 and 8 displayed the highest A and A adenosine receptor affinity with values below 7 μm. Both these compounds behaved as A 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 /A receptor antagonists that may have potential in treating both dementia and locomotor deficits in Parkinson's disease.