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

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.