Identification of a New Pyrazolo[1,5-a]quinazoline Ligand Highly Affine to γ-Aminobutyric Type A (GABAA) Receptor Subtype with Anxiolytic-Like and Antihyperalgesic Activity.

Abstract

Compounds that can act on GABAA receptor subtype in a selective manner, without the side effects of classical benzodiazepine ligands, represent promising therapeutic tools in neurological disorder as well as for relief of pain or in comorbidity of anxiety states and depression. Continuing our research on GABAA receptor subtype ligands, here is reported the synthesis of a series of pyrazolo[1,5-a]quinazoline 3- and/or 8-substituted as 5-deaza analogues of previous reported pyrazolo[5,1-c][1,2,4]benzotriazine, already identified as selective GABAA receptor subtype ligands endowed with anxiolytic-like and antihyperalgesic action or enhancer cognition. Between the new compounds stands out 12b for its high affinity value (Ki = 0.27 nM) and for its anxiolytic-like and ability to relieve neuropathic painful conditions evaluated in CCI and STZ murine model.