Synthesis, Physicochemical, and Anticonvulsant Properties of New N‐Mannich Bases Derived from Pyrrolidine‐2, 5‐dione and Its 3‐Methyl Analog. Issue 10 (19th August 2014)

• Record Type: Journal Article
• Authors: Rybka, Sabina; Obniska, Jolanta; Rapacz, Anna; Filipek, Barbara; Kamiński, Krzysztof
• Is Part Of: Archiv der Pharmazie. Volume 347:Issue 10(2014:Oct.)
• Page Start: 768
• Page End: 776
• Publication Date: 2014-08-19
• Subjects: Pharmaceutical chemistry -- Periodicals; Pharmacology -- Periodicals; 615.19
• DOI: 10.1002/ardp.201400152
• Languages: English
• ISSNs: 0365-6233

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="ardp201400152-sec-0001" sec-type="section"> <p>A series of 22 new <italic>N</italic>‐[(4‐phenylpiperazin‐1‐yl)‐methyl]‐3‐methyl‐pyrrolidine‐2, 5‐dione and pyrrolidine‐2, 5‐dione derivatives were synthesized and evaluated for their anticonvulsant activities in the maximum electroshock (MES) and subcutaneous pentylenetetrazole (<italic>sc</italic>PTZ) seizure tests after intraperitoneal injection into mice. The neurotoxicity was determined applying the rotarod test. The <italic>in vivo</italic> results in mice showed that seven compounds were effective in the MES or/and <italic>sc</italic>PTZ seizure tests. The quantitative evaluation in both tests after i.p. administration into mice revealed that the most active compounds were <italic>N</italic>‐[{4‐(3, 4‐dichlorophenyl)‐piperazin‐1‐yl}‐methyl]‐3‐methylpyrrolidine‐2, 5‐dione (<bold>12</bold>) with ED<sub>50</sub> = 16.13 mg/kg (MES), ED<sub>50</sub> = 133.99 mg/kg (<italic>sc</italic>PTZ) and <italic>N</italic>‐[{4‐(3, 4‐dichlorophenyl)‐piperazin‐1‐yl}‐methyl]‐pyrrolidine‐2, 5‐dione (<bold>23</bold>) with ED<sub>50</sub> = 37.79 mg/kg (MES), ED<sub>50</sub> = 128.82 mg/kg (<italic>sc</italic>PTZ), whereas <italic>N</italic>‐[{4‐(3‐trifluoromethylphenyl)‐piperazin‐1‐yl}‐methyl]‐pyrrolidine‐2, 5‐dione (<bold>24</bold>) was effective only in the MES test with ED<sub>50</sub> = 16.37 mg/kg. These molecules showed higher potency and also lower neurotoxicity than the reference antiepileptic drugs such as ethosuximide and valproic acid.</p> </sec> </abstract>