{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T02:47:17Z","timestamp":1789872437322,"version":"4.0.1"},"reference-count":36,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2014,9,5]],"date-time":"2014-09-05T00:00:00Z","timestamp":1409875200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2014,11]]},"abstract":"<jats:sec><jats:label\/><jats:p>Twenty\u2010two differently substituted 1<jats:italic>H<\/jats:italic>\u2010isoindole\u20101,3(2<jats:italic>H<\/jats:italic>)\u2010diones (<jats:bold>30<\/jats:bold>\u2013<jats:bold>39<\/jats:bold>), 8\u2010azaspiro[4.5]decane\u20107,9\u2010diones (<jats:bold>40<\/jats:bold>\u2013<jats:bold>45<\/jats:bold>), and 3\u2010azaspiro[5.5]undecane\u20102,4\u2010diones (<jats:bold>46<\/jats:bold>\u2013<jats:bold>51<\/jats:bold>) were synthesized and tested for anticonvulsant activity. These molecules were designed as analogs of previously obtained azaspirosuccinimides (<jats:bold>1<\/jats:bold>\u2013<jats:bold>24<\/jats:bold>). Initial anticonvulsant screening was performed in mice using the maximal electroshock (MES) and subcutaneous pentylenetetrazole (<jats:italic>sc<\/jats:italic>PTZ) seizure tests. The acute neurological toxicity was determined applying the minimal motor impairment rotorod test. The preliminary pharmacological results showed that 15 new compounds were effective in at least one animal model of epilepsy, from which nine molecules showed protection against both MES and<jats:italic>sc<\/jats:italic>PTZ seizures. The structure\u2013activity relationship analysis revealed that anticonvulsant activity was connected closely with the structure of the imide fragment; the most favorable one was the hexahydro\u20101<jats:italic>H<\/jats:italic>\u2010isoindole\u20101,3(2<jats:italic>H<\/jats:italic>)\u2010dione core. 2\u2010(2\u2010Chlorophenyl)hexahydro\u20101<jats:italic>H<\/jats:italic>\u2010isoindole\u20101,3(2<jats:italic>H<\/jats:italic>)\u2010dione (<jats:bold>31<\/jats:bold>) showed activity in the 6\u2010Hz psychomotor seizure model, which identifies substances effective in partial and therapy\u2010resistant epilepsy. 3\u2010[(4\u2010Chlorophenyl)amino]\u20103\u2010azaspiro[5.5]undecane\u20102,4\u2010dione (<jats:bold>47<\/jats:bold>) was active in the<jats:italic>in vitro<\/jats:italic>hippocampal slice culture neuroprotection assay.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ardp.201400179","type":"journal-article","created":{"date-parts":[[2014,9,5]],"date-time":"2014-09-05T10:33:27Z","timestamp":1409913207000},"page":"840-852","source":"Crossref","is-referenced-by-count":17,"title":["Synthesis, Anticonvulsant Properties, and SAR Analysis of Differently Substituted Pyrrolidine\u20102,5\u2010diones and Piperidine\u20102,6\u2010diones"],"prefix":"10.1002","volume":"347","author":[{"given":"Krzysztof","family":"Kami\u0144ski","sequence":"first","affiliation":[{"name":"Department of Medicinal Chemistry Jagiellonian University Medical College Krak\u00f3w Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beata","family":"Wiklik","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry Jagiellonian University Medical College Krak\u00f3w Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jolanta","family":"Obniska","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry Jagiellonian University Medical College Krak\u00f3w Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,9,5]]},"reference":[{"key":"e_1_2_6_2_1","volume-title":"The Goodman & Gilman's the Phamacological Basis of Therapeutics","author":"McNamara J. 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