GABA A Receptor Modulators with a Pyrazolo[1,5-a]quinazoline Core: Synthesis, Molecular Modelling Studies and Electrophysiological Assays.

As a continuation of our study in the GABA A receptor modulators field, we report the design and synthesis of new 8-chloropyrazolo[1,5-a]quinazoline derivatives. Molecular docking studies and the evaluation of the 'Proximity Frequencies' (exploiting our reported model) were performed on all the final compounds ( 3 , 4 , 6a - c , 7a , b , 8 , 9 , 12a - c , 13a , b , 14 - 19 ) to predict their profile on the α1β2γ2-GABA A R subtype. Furthermore, to verify whether the information coming from this virtual model was valid and, at the same time, to complete the study on this series, we evaluated the effects of compounds (1-100 µM) on the modulation of GABA A receptor function through electrophysiological techniques on recombinant α1β2γ2L-GABA A receptors expressed in Xenopus laevis oocytes. The matching between the virtual prediction and the electrophysiological tests makes our model a useful tool for the study of GABA A receptor modulators.