Abstract
A series of new 1-(thiazol-2-yl)pyrrolidin-2-one 5a-m and 2-(thiazol-2-yl)isoindoline-1,3-dione 6a-n derivatives were synthesized and evaluated for anticonvulsant activity. The activity was established in three seizure models: PTZ, picrotoxin and MES. Selected compounds were elected for neurotoxicity by the rotarod test. The most active compound of the series was 1-(4-(naphthalen-2-yl)thiazol-2-yl)pyrrolidin-2-one (5g), showing a PTZ effect dose (ED50) value of 18.4 mg/kg in mice. The median toxic dose (TD50) was 170.2 mg/kg, which provided a protection index (PI = TD50/ED50) of 9.2. A computational study was also carried out, including prediction of pharmacokinetic properties and docking studies. The structural assignments of the newly synthesized compounds were elucidated on the basis of spectroscopic data and single-crystal X-ray crystallography.
A series of new thiazole-based pyrrolidinones 5a-m and isoindolinediones 6a-l were synthesized and tested as anticonvulsant. The most active compound was 1-(4-(naphthalen-2-yl)thiazol-2-yl)pyrrolidin-2-one (5g), showing ED50 value 18.4 mg/kg.
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