Journal
CHEMMEDCHEM
Volume 4, Issue 6, Pages 1010-1019Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cmdc.200800434
Keywords
adenosine; antagonists; molecular modeling; purine derivatives; receptors
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Funding
- Italian Ministry for University and Research [FIRB RBN503YA3L]
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Clinical evidence has demonstrated that AA,,R antagonists could be an alternative approach to the treatment of Parkinson's disease. Recently, three 9-ethyladenine derivatives bearing a bromine atom, an ethoxy group, and a furyl ring, respectively, in the 8-position have been reported to ameliorate motor deficits in rat Parkinson's disease models, suggesting a potential therapeutic role for these compounds. Starting from these observations, a new series of 9-ethyladenine derivatives, bearing different substituents such as halogens, alkoxy groups, aromatic and heteroaromatic rings in the 8-position, were synthesized. Radioligand binding assays demonstrated that some of the new compounds bind rat AA,,R with higher affinity than the previously reported congeners and that there is a good correlation between binding to rat and human receptors. Hence, the new molecules could represent new tools suitable for the in vivo studies in rat models of Parkinson's disease. Finally, a molecular docking analysis of the compounds was performed using a homology model of rat AA(2A)R, built using the human crystal structure as the template, and results are in agreement with the binding data.
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