Synthesis and Biological Activity of Trisubstituted Adenines as A_2A Adenosine Receptor Antagonists

Abstract

The discovery of new drugs for the treatment of neurodegenerative disorders, such as Parkinson's disease, has become an attractive field of research. Due to the regulation of D ₂ receptor activity by A _{2 A} adenosine receptor, potent and selective ligands of A _{2 A} subtype could be useful tools to study neurodegenerative disorders. A series of 2,8-disubstituted-9-ethyladenine derivatives was synthesized and tested in binding affinity assay at human adenosine receptors. New compounds showed good affinity and selectivity at A _{2 A} receptor versus the other subtypes. The introduction of a bromine atom in 8-position increased the affinity of these compounds, leading to ligands with K _i in the nanomolar range.

Keywords:

• Adenosine receptor ligands
• adenosine receptor antagonits
• A_2A antagonists
• 9-ethylpurine derivatives
• substituted adenines

This work was supported by Fondo di Ricerca di Ateneo (University of Camerino) and by grants from the Italian Ministry of Research: FIRB 2001, FIRB 2003, and PRIN 2005.

Notes

^a 95% confidence intervals in parentheses.