Semenets A. Molecular modeling and synthesis of biologically active substances with nootropic action in a series of 4-R-1-benzylpyrrolidin-2-one derivatives

The dissertation work is devoted to the search for new biologically active substances in a number of 4-R-1-benzylpyrrolidin-2-one derivatives, to the study of their nootropic properties using in silico and in vivo methods. For the first time, within the framework of the dissertation research, optimal directions of structural modification were determined and preparative methods for the synthesis of target derivatives were developed. Using the methodology of molecular docking and experimental screening, the prospect of finding nootropic substances in the investigated series of substances was confirmed. The discovery of the most promising compound 1-benzyl-4-{4-[2-oxo-2-(piperidin-1-yl)ethyl]-5-sulfanilidene-4,5-dihydro-1H-1,2,4-triazol-3-yl}pyrrolidin-2-one, which has a distinct nootropic (anti-amnestic) activity that exceeds the indicators of the reference drug Piracetam by more than 2 times and has favorable ADMET properties calculated in silico. The compound can be obtained in the conditions of a chemical-pharmaceutical enterprise using available technology, which allows predicting the possibility of its use in medical practice for the treatment of cognitive dysfunctions.