Synthesis, anticonvulsant activity and molecular modeling study of some new hydrazinecarbothioamide, benzenesulfonohydrazide, and phenacylacetohydrazide analogues of 4(3H)-quinazolinone

A new series of quinazoline analogues was designed and synthesized to get the target compounds 18–21, 30–41, 46–53, and 57–76. The Obtained compounds were evaluated for their anticonvulsant activity using PTZ and picrotoxin convulsive models. Compounds 47, 63, 68 and 73 proved to be the most active compounds in this study with a remarkable 100% protection against PTZ induced convulsions. Compounds 47, 63, 68 and 73 proved to be 10, 4, 4, and 5 fold more active, respectively than the used positive control sodium valproate. Structure activity correlation concluded valuable pharmacophoric information which confirmed by molecular modeling studies. Molecular docking study of 68 suggested its agonistic behavior toward GABAA receptor. The studied quinazoline analogues could be considered as useful templates for future development and further derivatization.

Structures of compounds 47, 63, 68 and 73, the most active anticonvulsants with a remarkable 100% protection against PTZ induced convulsions.Figure optionsDownload as PowerPoint slide