New acetamide derivatives of quinazoline-2,4(1H,3H)-dione: neural network prediction, synthesis, and psychotropic activity

Multiple docking of five new acetamide derivatives of 1-methylquinazoline-2,4(1H,3H)-dione was carried out over the entire GABAA receptor (gamma-butyric acid type A receptor) and the energy spectra of multiple docking were calculated. Using a model based on multiple docking and artificial neural networks technology, the level of GABAA agonistic activity of these compounds was predicted. One promising compound with possible high GABAA agonistic activity was identified. Synthesis of five new acetamide derivatives of 1-methylquinazorine-2,4(1H,3H)-dione was accomplished. The psychotropic activity of the synthesized compounds was studied in the open field behavioral test. One compound was found to have a pronounced priming effect, comparable to that of the reference drug diazepam. This active compound was recommended for further in-depth study of its anxiolytic and antidepressant properties. The predictive accuracy of the technology developed in silico was 100%, which allowed us to recommend it for a directed search for innovative drugs with various types of pharmacological action.