A new series of 3,6-disubstituted pyrazolo[1,5-a]quinazolines (PQs) 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, have been synthesized and evaluated. These new compounds have been obtained exploiting a different synthetic pathway with respect to the corresponding 3,8-disubstituted 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
Daniele S.;Martini C.;
2019-01-01
Abstract
A new series of 3,6-disubstituted pyrazolo[1,5-a]quinazolines (PQs) 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, have been synthesized and evaluated. These new compounds have been obtained exploiting a different synthetic pathway with respect to the corresponding 3,8-disubstituted 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
