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

Journal of Enzyme Inhibition and Medicinal Chemistry
Gabriella GuerriniMaria Paola Giovannoni

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).

References

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Mar 8, 2005·Biophysical Journal·Megan O'MaraShin-Ho Chung
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May 6, 2014·Bioorganic & Medicinal Chemistry Letters·Cody J WenthurCraig W Lindsley

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Citations

Feb 27, 2017·Bioorganic & Medicinal Chemistry·Gabriella GuerriniSilvia Selleri
Feb 28, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Blanca Angelica Vega AlanisMarko D Mihovilovic
Dec 29, 2020·Bioorganic & Medicinal Chemistry Letters·Letizia CrocettiMaria Paola Giovannoni
Nov 22, 2020·Bioorganic & Medicinal Chemistry·Niccolò CantiniMaria Paola Giovannoni

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