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).
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 / Gabriella Guerrini; Giovanna Ciciani; Samuele Ciattini; Letizia Crocetti; Simona Daniele; Claudia Martini; Fabrizio Melani; Claudia Vergelli; Maria Paola Giovannoni. - In: JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY. - ISSN 1475-6366. - ELETTRONICO. - 31:(2016), pp. 195-204. [10.3109/14756366.2015.1014475]
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
GUERRINI, GABRIELLA;CICIANI, GIOVANNA;CIATTINI, SAMUELE;CROCETTI, LETIZIA;MELANI, FABRIZIO;VERGELLI, CLAUDIA;GIOVANNONI, MARIA PAOLA
2016
Abstract
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).File | Dimensione | Formato | |
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