Synthesis and anticonvulsant activity of 7-phenyl-6,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidin-5(4H)-ones and their derivatives

Herein, we described the syntheses and anticonvulsant activities of 7-(substituted-phenyl)-6,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidin-5(4H)-ones (1a–1o) and their derivatives. Most of the synthesized compounds exhibited potent anticonvulsant activities in the maximal electroshock test (MES). The most promising compound 1i showed significant anticonvulsant activity in MES test with ED50 value of 19.7 mg/kg. It displayed a wide margin of safety with protective index much higher than the standard drugs. In addition, the potence of compound 1i against seizures induced by Pentylenetetrazole, Isoniazid, Thiosemicarbazide, 3-Mercaptopropionic acid, and Bicuculline in the chemical-induced seizure tests suggested that compound 1i displayed broad spectrum activity in several models, and it is likely to have several mechanisms of action including inhibiting voltage-gated ion channels and modulating GABAergic activity.

Graphical abstractA series of novel 7-phenyl-6,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidin-5(4H)-ones and its derivatives were synthesized and their anticonvulsant effects on mice were assessed. Their structure–activity relationships were also discussed.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights►7-(Substituted-phenyl)-6,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidin-5(4H)-one derivatives were synthesized.►Their good anticonvulsant activities were found including the best one 1i (ED50 19.7 mg/kg and PI 34.8).►Compounds possessing a triazole displayed better activity and PI than others.►Compound 1i displayed broad spectrum activity in several models.