کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1363891 | 981524 | 2008 | 11 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Design, synthesis, and anticonvulsant activity of N-phenylamino derivatives of 3,3-dialkyl-pyrrolidine-2,5-diones and hexahydro-isoindole-1,3-diones Design, synthesis, and anticonvulsant activity of N-phenylamino derivatives of 3,3-dialkyl-pyrrolidine-2,5-diones and hexahydro-isoindole-1,3-diones](/preview/png/1363891.png)
In the present study on the development of new anticonvulsants, the library of differently substituted N-phenylamino pyrrolidine-2,5-dione and hexahydro-isoindole-1,3-dione derivatives was synthesized. The anticonvulsant activity of all the compounds was evaluated using the maximal electroshock (MES) and pentylenetetrazole (scPTZ) screens, which are the most widely employed seizure models for early identification of candidate anticonvulsants. Their neurotoxicity was determined applying the rotorod test. The pharmacological results revealed that the majority of compounds were effective in electrical (MES) and/or pentylenetetrazole induced seizure (scPTZ) models. The quantitative in vivo anticonvulsant evaluation of N-phenylamino-3,3-dimethyl-pyrrolidine-2,5-dione (15), conducted at the time of peak pharmacodynamic activity (TPE), showed the MES ED50 value of 69.89 mg/kg in rats. The median toxic dose (TD50) was 500 mg/kg, providing compound 15 with a protective index (TD50/ED50) of 7.15 in the MES test.
The majority of compounds investigated showed activity in the MES and scPTZ screens the most widely employed seizure models for early identification of candidate anticonvulsants.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry - Volume 16, Issue 9, 1 May 2008, Pages 4921–4931