New 3,6‐Disubstituted Pyrazolo[1,5‐ a ]quinazolines as Ligands to GABA A Receptor Subtype

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 GABA A 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.