Pyrazolo[1,5-a]quinazoline scaffold as 5-deaza analogue of pyrazolo[5,1-c][1,2,4]benzotriazine system: synthesis of new derivatives, biological activity on GABA<sub>A</sub> receptor subtype and molecular dynamic study

<div><p></p><p>To investigate the binding affinity of GABA<sub>A</sub> receptor subtype, new pyrazolo [1,5-a]quinazolines were designed, synthesized, and <i>in vitro</i> evaluated. These compounds, 5-deaza analogues of pyrazolo[5,1-c][1,2,4]benzotriazine derivatives which were already studied in our research group, permit us to evaluate the relevance of the nitrogen or the oxygen atom at 5-position of the tricyclic scaffold. Molecular dynamic study was done on a set of the new and known ligands to rationalize and to explain the lack of affinity on the 4- or 5-substituted new derivative. In fact, from biological results, it can be found that the only 5-unsubstituted new derivative, compound <b>15</b>, has receptor recognition (<i>K<sub>i</sub></i> = 834.7 nM).</p></div>