Synthesis and anticonvulsant activity of novel purine derivatives

•Purine derivatives were synthesized.•Their anticonvulsant activities were evaluated.•Compound 5e showed significant anticonvulsant activity.•Compound 5e was evaluated in the sc-PTZ-induced seizures tests.•Compound 5e was proposed to be a promising anticonvulsant agent.

A series of new purines containing triazole and other heterocycle substituents was synthesized and evaluated for their preliminary anticonvulsant activity and neurotoxicity by using the maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ) and rotarod neurotoxicity (TOX) tests. Among the compounds studied, 9-decyl-6-(1H-1,2,4-triazol-1-yl)-9H-purine (5e) was the most potent compound, with a median effective dose of 23.4 mg/kg and a high protective index of more than 25.6 after intraperitoneal administration in mice. Compound 5e showed significant oral activity against MES-induced seizures in mice, with an ED50 of 39.4 mg/kg and a PI above 31.6. These results demonstrate that compound 5e possesses better anticonvulsant activity and is safer than the commercially available drugs carbamazepine and valproate in MES, scPTZ and TOX models.

Graphical abstractA series of new purines containing triazole and other heterocycle substituents was synthesized and evaluated for their anticonvulsant activity and neurotoxicity by using the maximal electroshock (MES) and rotarod tests.Figure optionsDownload full-size imageDownload as PowerPoint slide