El-Helby A.G.A.Ayyad R.R.Sakr H.M.Abdelrahim A.S.El-Adl K.Sherbiny F.S.Eissa I.H.Khalifa M.M.Pharmaceutical Chemistry DepartmentFaculty of Pharmacy (Boys)Al-Azhar UniversityCairo11884Egypt; Pharmaceutical Chemistry DepartmentFaculty of PharmacyDelta University for Science and TechnologyGamasaDakahliaEgypt; Organic Chemistry DepartmentFaculty of PharmacyAl-Azhar University (Boys)Cairo11884Egypt; Organic Chemistry DepartmentFaculty of PharmacyOctober University for Modern Science and Arts (MSA)6th October City11787Egypt2020-01-092020-01-092017222860https://doi.org/10.1016/j.molstruc.2016.10.052PubMed ID :https://t.ly/0E37lScopusIn view of their expected anticonvulsant activity, some novel derivatives of 2,3-dihydrophthalazine-1,4-dione 4�22 were designed, synthesized and evaluated using pentylenetetrazole (PTZ) and picrotoxin as convulsion-inducing models. Moreover, the most active compounds were tested against electrical induced convulsion using maximal electroshock (MES) models of seizures. Most of the tested compounds showed considerable anticonvulsant activity in at least one of the anticonvulsant tests. Compounds 13 and 14g were proved to be the most potent compounds of this series with relatively low toxicity in the median lethal dose test when compared with the reference drug. Molecular modeling studies were done to verify the biological activity. The obtained results showed that the most potent compounds could be useful as a template for future design, optimization, and investigation to produce more active analogues. 2016 Elsevier B.V.English2,3-Dihydrophthalazine-1,4-dioneAnticonvulsantGABA-AMolecular modelingBioactivityDrug dosageMolecular modeling2,3-Dihydrophthalazine-1,4-dioneActive compoundsAnticonvulsantAnticonvulsant activityBiological evaluationMedian lethal doseMolecular modeling studiesPotent compoundsDrug productsArticlehttps://doi.org/10.1016/j.molstruc.2016.10.052PubMed ID :