Selective adenosine receptor modulators are potential tools for numerous therapeutic applications, including cardiovascular, inflammatory, and neurodegenerative diseases. In this work, the synthesis and biological evaluation at the four human adenosine receptor subtypes of a series of 9-substituted 8-(2-furyl)adenine derivatives are reported. Results show that 8-(2-furyl)-9-methyladenine is endowed with high affinity at the A₂A subtype. Further modification of this compound with introduction of arylacetyl or arylcarbamoyl groups in N(6)-position takes to different effects on the A₂A affinity and in particular on the selectivity versus the other three adenosine receptor subtypes. A molecular modelling analysis at three different A₂A receptor crystal structures provides an interpretation of the obtained biological results.
Keywords: AR; Adenine derivatives; Adenosine receptor antagonists; Adenosine receptors; CHO; CNS; Chinese hamster ovary; DMF; EL; G protein-coupled receptor; GPCR; IL; IR; MOE; Molecular modelling; N-bromosuccinimide; NBS; Purine derivatives; Purinergic receptors; RMSD; THF; TLC; TM; adenosine receptor; central nervous system; dimethylformamide; extracellular loop; infrared; intracellular loop; molecular operating environment; pdb; protein data bank; root mean square deviation; tetrahydrofuran; thin-layer chromatography; transmembrane.
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