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Their anticonvulsant activity was evaluated in standard animal models of epilepsy: the maximal electroshock (MES), the 6\u2005Hz, and the subcutaneous pentylenetetrazole (<jats:italic>sc<\/jats:italic>PTZ) tests. The <jats:italic>in\u2005vivo<\/jats:italic> studies revealed the most potent anticonvulsant activity for <jats:bold>15<\/jats:bold> (3\u2010(<jats:italic>sec<\/jats:italic>\u2010butyl)\u20101\u2010(2\u2010(4\u2010(3\u2010trifluoromethylphenyl)piperazin\u20101\u2010yl)\u20102\u2010oxoethyl)pyrrolidine\u20102,5\u2010dione), with ED<jats:sub>50<\/jats:sub> values of 80.38\u2005mg\/kg (MES) and 108.80\u2005mg\/kg (6\u2005Hz). The plausible mechanism of action was assessed in <jats:italic>in\u2005vitro<\/jats:italic> binding assays, in which <jats:bold>15<\/jats:bold> interacted effectively with voltage\u2010gated sodium (site 2) and L\u2010type calcium channels at a concentration of 100\u2005\u03bcM. Subsequently, the antinociceptive activity of compounds <jats:bold>7<\/jats:bold> and <jats:bold>15<\/jats:bold> was observed in the hot plate test of acute pain. Moreover, compounds <jats:bold>7<\/jats:bold>, <jats:bold>11<\/jats:bold> and <jats:bold>15<\/jats:bold> demonstrated an analgesic effect in the formalin test of tonic pain. The hepatotoxic properties of the most effective compounds (<jats:bold>7<\/jats:bold>, <jats:bold>11<\/jats:bold> and <jats:bold>15<\/jats:bold>) in HepG2 cells were also investigated.<\/jats:p>","DOI":"10.1002\/cmdc.202001007","type":"journal-article","created":{"date-parts":[[2021,2,6]],"date-time":"2021-02-06T01:48:11Z","timestamp":1612576091000},"page":"1619-1630","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Design, Synthesis and Biological Activity of New Amides Derived from 3\u2010Benzhydryl and 3\u2010<i>sec<\/i>\u2010Butyl\u20102,5\u2010dioxo\u2010pyrrolidin\u20101\u2010yl\u2010acetic Acid"],"prefix":"10.1002","volume":"16","author":[{"given":"Ma\u0142gorzata","family":"G\u00f3ra","sequence":"first","affiliation":[{"name":"Department of Medicinal Chemistry Jagiellonian University Medical College Faculty of Pharmacy  Medyczna 9 30-688 Krak\u00f3w Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1448-9826","authenticated-orcid":false,"given":"Anna","family":"Czopek","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry Jagiellonian University Medical College Faculty of Pharmacy  Medyczna 9 30-688 Krak\u00f3w Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Rapacz","sequence":"additional","affiliation":[{"name":"Department of Pharmacodynamics Jagiellonian University Medical College Faculty of Pharmacy  Medyczna 9 30-688 Krak\u00f3w Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Giza","sequence":"additional","affiliation":[{"name":"Department of Pharmacodynamics Jagiellonian University Medical College Faculty of Pharmacy  Medyczna 9 30-688 Krak\u00f3w Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulina","family":"Koczurkiewicz\u2010Adamczyk","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biochemistry Jagiellonian University Medical College Faculty of Pharmacy  Medyczna 9 30-688 Krak\u00f3w Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"El\u017cbieta","family":"P\u0119kala","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biochemistry Jagiellonian University Medical College Faculty of Pharmacy  Medyczna 9 30-688 Krak\u00f3w Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jolanta","family":"Obniska","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry Jagiellonian University Medical College Faculty of Pharmacy  Medyczna 9 30-688 Krak\u00f3w Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krzysztof","family":"Kami\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry Jagiellonian University Medical College Faculty of Pharmacy  Medyczna 9 30-688 Krak\u00f3w Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,3,2]]},"reference":[{"key":"e_1_2_7_1_1","doi-asserted-by":"crossref","unstructured":"E. 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