A new series of 3,6-disubstituted pyrazolo[1,5-a]quinazolines (PQ) and their 4,5-dihydro derivatives as isomer of the potent 3,8-PQ previously reported by us as high affine GABAA receptor subtype ligands, has been synthesized and evaluated. These new compounds have been obtained exploiting a different synthetic pathway with respect to the corresponding 3,8-disubstitued isomers, proposing again the same groups present in the reference 3,8-PQ. The movement of the substituents from position 8 to position 6 is detrimental for binding recognition, suggesting that the substituents at position 6 are not properly oriented to form adequate interaction with hydrogen bond point and lipophilic area in the receptor protein, as demonstrated in molecular modeling studies.

New 3,6-disubstituted pyrazolo[1,5-a]quinazolines as ligands to GABAA receptor subtype / Gabriella Guerrini, Letizia Crocetti, Simona Daniele, Antonella Iacovone, Niccolò Cantini,Claudia Martini, Fabrizio Melani, Claudia Vergelli, Maria Paola Giovannoni,. - In: JOURNAL OF HETEROCYCLIC CHEMISTRY. - ISSN 1943-5193. - ELETTRONICO. - 56:(2019), pp. 1571-1580. [10.1002/jhet.3535]

New 3,6-disubstituted pyrazolo[1,5-a]quinazolines as ligands to GABAA receptor subtype

Gabriella Guerrini;Letizia Crocetti;Niccolò Cantini;Fabrizio Melani;Claudia Vergelli;Maria Paola Giovannoni
2019

Abstract

A new series of 3,6-disubstituted pyrazolo[1,5-a]quinazolines (PQ) and their 4,5-dihydro derivatives as isomer of the potent 3,8-PQ previously reported by us as high affine GABAA receptor subtype ligands, has been synthesized and evaluated. These new compounds have been obtained exploiting a different synthetic pathway with respect to the corresponding 3,8-disubstitued isomers, proposing again the same groups present in the reference 3,8-PQ. The movement of the substituents from position 8 to position 6 is detrimental for binding recognition, suggesting that the substituents at position 6 are not properly oriented to form adequate interaction with hydrogen bond point and lipophilic area in the receptor protein, as demonstrated in molecular modeling studies.
2019
56
1571
1580
Gabriella Guerrini, Letizia Crocetti, Simona Daniele, Antonella Iacovone, Niccolò Cantini,Claudia Martini, Fabrizio Melani, Claudia Vergelli, Maria Pa...espandi
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1150858
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