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Compounds that can act on GABA A 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 GABA A 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 GABA A 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 (K i = 0.27 nM) and for its anxiolytic-like and ability to relieve neuropathic painful conditions evaluated in CCI and STZ murine model.

journal of medicinal chemistry

Identification of a New Pyrazolo[1,5-<i>a</i>]quinazoline Ligand Highly Affine to γ-Aminobutyric Type A (GABA<sub>A</sub>) Receptor Subtype with Anxiolytic-Like and Antihyperalgesic Activity

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

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