To investigate the binding affinity of GABAA receptor subtype, new pyrazolo [1,5-a]quinazolines were designed, synthesized, and in vitro 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 15, has receptor recognition (Ki = 834.7 nM).
|Autori:||Guerrini, G; Ciciani, G; Ciattini, S; Crocetti, L; Daniele, S; Martini, C; Melani, F; Vergelli, C; Giovannoni, Mp|
|Titolo:||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 GABAA receptor subtype and molecular dynamic study.|
|Anno del prodotto:||2015|
|Digital Object Identifier (DOI):||10.3109/14756366.2015.1014475|
|Appare nelle tipologie:||1.1 Articolo in rivista|