Exploring the QSAR of pyrazolo[3,4-b]pyridine, pyrazolo[3,4-b]pyridone and pyrazolo[3,4-b]pyrimidine derivatives as antagonists for A1 adenosine receptor.

Pyrazolo[3,4-b]pyridines have been recently presented as a novel class of adenosine A1 receptor antagonists. Depending on substitutions on some key positions of their scaffold they show selectivity towards A1, A2A or A3 receptors, which results in a variety of therapeutic potentialities of these ligands. In this work, we present a QSAR study on these analogues as antagonists for adenosine A1 receptors. Using the MOE software we identified a pool of descriptors that numerically describes the ligand features impacting the affinity at adenosine A1 receptors. The obtained information is useful to understand the main structural features that strongly correlate with the A1 antagonism in this class of compounds and will be used for the rational design of more potent and selective pyrazolo[3,4-b]pyridine derivatives.