Simplification of Pyrazolo-triazolo-pyrimidine Nucleus for Searching New Adenosine Receptor Antagonists.

Blockade of adenosine receptors (ARs) lead to a broad variety of effects in several organ systems permitting to consider antagonists for ARs as potential therapeutic targets. Several classes of heterocyclic derivatives have been reported as ARs antagonists with high levels of both affinity and selectivity. [1] In particular, in the last years, the nucleus of pyrazolo-triazolo-pyrimidines as ARs antagonists was deeply investigated. Modulating the substitution at the N5, N7 and N8 positions potent and selective A2A (1) and A3 (2) ARs antagonists have been synthesized.[2,3] Nevertheless this class of compounds, such as other tricyclic structures, showed several problems such as poor water solubility and most importantly tangled synthetic preparation. On these bases we tried to simplify the nucleus in order to avoid the problems related to this structure. In particular we developed triazolo-triazines [4], triazolopyrimidines and the extremely basic arylstyrenes derivatives. All the obtained results will be summarized.