| Abstract
| - A number of 4-aminopyrazolo[3,4-b]pyridines 5-carboxylic acid esters (2−8) were synthesizedand evaluated for their binding affinity at the A1, A2A, and A3 adenosine receptors (AR), inbovine cortical membranes, as well as for their affinity toward human A1AR (hA1AR). Some ofthe new compounds were characterized by a high affinity and selectivity toward the A1 receptorsubtype, showing a significant improvement in comparison with other pyrazolo-pyridinespreviously reported in the literature. In particular the methyl ester 2h as well as the isopropylester 5h, both of them bearing a p-methoxyphenylethylamino side chain at the position 4,presented Ki values of 6 and 7 nM, respectively. To rationalize the relationships betweenstructure and affinity of the novel compounds, a 3D QSAR model was also generated startingfrom compounds belonging to different classes of known A1AR antagonists.
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