8-Bromo-9-alkyl adenine derivatives as tools for developing new adenosine A2A and A2B receptors ligands

Importance of making available selective adenosine receptor antagonists is boosted by recent findings of adenosine involvement in many CNS dysfunctions. In the present work a series of 8-bromo-9-alkyl adenines are prepared and fully characterized in radioligand binding assays or functional cyclase experiments in respect to their interaction with all the four adenosine receptor subtypes. Results show that the presence of the bromine atom in 8-position of 9-substituted adenines promotes in general the interaction with the adenosine receptors, in particular at the A2A subtype. The present study also demonstrates that adenine derivatives could be a good starting point to obtain selective adenosine A2B receptor antagonists.

The development of potent antagonists selective for the different adenosine receptor subtypes has been a subject of medicinal chemistry research in the last decade and the recent findings of adenosine involvement in many CNS dysfunctions make of utmost importance to have adenosine receptor ligands available with different physical–chemical properties. Herein we report the preparation and the chemical and in vitro characterization of a series of 9-alkyladenines and of the corresponding 8-bromo derivatives, which resulted to be good starting point to develop selective adenosine A2A and A2B receptor antagonists.Figure optionsDownload as PowerPoint slide