E/Z Isomerism of the Potential Antiepileptic Drug GIZH-298

The synthesis, purification, and comprehensive characterization of the E- and Z-isomers of the prospective anticonvulsant compound GIZH-298 were carried out. It was demonstrated that both isomers could be obtained in a pure form by isolating the corresponding oximes at the initial stage of synthesis. The E- and Z-isomers exhibit pronounced differences in their physicochemical characteristics, spectral features, and pharmacological profiles. Z-GIZH-298 was found to be photosensitive, undergoing Z-E isomerization upon irradiation, as confirmed by both theoretical analysis and experimental observations. Additionally, partial conversion to the E-form occurs during prolonged reflux of Z-GIZH-298 in polar solvents, whereas the compound remains stable in aqueous and acidic media at ambient temperature. In the maximal electroshock assay, both isomers demonstrated anticonvulsant activity, with Z-GIZH-298 showing substantially higher efficacy than its E-counterpart. These findings highlight the need to account for potential E-isomer formation when considering further development of Z-GIZH-298 as a promising anticonvulsant agent.