Design, Synthesis and In Silico Evaluation of a Novel Pyrimidine Derivative (5b) as a Potential Anticonvulsant Agent

Abstract

Epilepsy is a chronic neurological disorder characterized by recurrent seizures and remains a major global health concern. In the present study, a novel pyrimidine derivative (5b) was designed, synthesized, and evaluated for its anticonvulsant potential. The compound was synthesized via Claisen–Schmidt condensation followed by cyclization and was characterized using standard spectroscopic techniques. Molecular docking studies were performed against γ-aminobutyric acid aminotransferase (GABA-AT) (PDB ID: 1OHW) to investigate binding interactions. Compound 5b exhibited a binding energy of −8.0 kcal/mol with key interactions involving Ser137A and Lys329A. The compound was further evaluated using MES and scPTZ seizure models in mice. Results indicated moderate anticonvulsant activity with acceptable safety profile. The study suggests that compound 5b can serve as a potential lead for further structural optimization in the development of anticonvulsant agents.