title: 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.
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).
authors: a Dipartimento NEUROFARBA , Sezione Farmaceutica e Nutraceutica, Università degli Studi di Firenze , Firenze , Italy .
authors: Gabriella
authors: G
authors: Guerrini
authors: a Dipartimento NEUROFARBA , Sezione Farmaceutica e Nutraceutica, Università degli Studi di Firenze , Firenze , Italy .
authors: Giovanna
authors: G
authors: Ciciani
authors: b Dipartimento di Chimica , Centro di Cristallografia, Università degli Studi di Firenze , Firenze , Italy , and.
authors: Samuele
authors: S
authors: Ciattini
authors: a Dipartimento NEUROFARBA , Sezione Farmaceutica e Nutraceutica, Università degli Studi di Firenze , Firenze , Italy .
authors: Letizia
authors: L
authors: Crocetti
authors: c Dipartimento di Farmacia , Università degli Studi di Pisa , Pisa , Italy.
authors: Simona
authors: S
authors: Daniele
authors: c Dipartimento di Farmacia , Università degli Studi di Pisa , Pisa , Italy.
authors: Claudia
authors: C
authors: Martini
authors: a Dipartimento NEUROFARBA , Sezione Farmaceutica e Nutraceutica, Università degli Studi di Firenze , Firenze , Italy .
authors: Fabrizio
authors: F
authors: Melani
authors: a Dipartimento NEUROFARBA , Sezione Farmaceutica e Nutraceutica, Università degli Studi di Firenze , Firenze , Italy .
authors: Claudia
authors: C
authors: Vergelli
authors: a Dipartimento NEUROFARBA , Sezione Farmaceutica e Nutraceutica, Università degli Studi di Firenze , Firenze , Italy .
authors: Maria Paola
authors: MP
authors: Giovannoni
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002417:Cattle; D060326:Chemistry Techniques, Synthetic; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006860:Hydrogen Bonding; D056004:Molecular Dynamics Simulation; D025341:Principal Component Analysis; D011799:Quinazolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D011799:Quinazolines; D011963:Receptors, GABA-A
keywords: Fused tricyclic system; GABAA subtype receptor affinity; molecular modeling study; pyrazolobenzotriazine; pyrazoloquinazoline