Design, Synthesis, Structure and Biological Activity of New Five-Membered Heterocyclic Systems Based on 2,7-Naphthyridines: A New Class of Psychotropic Compounds.

As part of our ongoing research in heterocyclic chemistry, we report herein the synthesis of novel pentaheterocyclic systems that integrate pyrrolo[1,2-a]pyrimidine, pyrido[1,2-a]pyrimidine, or pyrimido[1,2-a]azepine fragments with a 2,7-naphthyridine moiety within a single molecular framework. These compounds represent promising scaffolds for drug discovery. The synthetic approach commenced from the corresponding amines and ethyl acrylate and involved a sequence of nucleophilic substitution and cyclization reactions. The structures of the synthesized compounds were elucidated using spectroscopic techniques and unambiguously confirmed by single-crystal X-ray diffraction analysis. Biological evaluation revealed that the newly synthesized 2,7-naphthyridine-based systems exhibit neuroprotective activity. Although they displayed only weak anticonvulsant effects in the pentylenetetrazole-induced seizure model, they demonstrated notable anxiolytic and antidepressant properties, highlighting their potential as lead compounds for the development of novel neuroactive agents. Furthermore, molecular docking studies were performed, and the results were found to be consistent with the experimental findings.