{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T20:23:30Z","timestamp":1773087810906,"version":"3.50.1"},"reference-count":29,"publisher":"Wiley","issue":"3-4","license":[{"start":{"date-parts":[[2017,3,20]],"date-time":"2017-03-20T00:00:00Z","timestamp":1489968000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Polish National Scientific Centre, Poland","award":["DEC-2013\/11\/B\/NZ7\/02081"],"award-info":[{"award-number":["DEC-2013\/11\/B\/NZ7\/02081"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2017,4]]},"abstract":"<jats:sec><jats:label\/><jats:p>The focused library of new amides derived from 3,3\u2010diphenyl\u20102,5\u2010dioxo\u2010pyrrolidin\u20101\u2010yl\u2010acetic acid (<jats:bold>2a\u2013t<\/jats:bold>) and 3,3\u2010diphenyl\u2010propionic acid (<jats:bold>3a\u2013t<\/jats:bold>) as potential anticonvulsant agents was synthesized. The final products were obtained in the amidation reaction of the given carboxylic acid (<jats:bold>2<\/jats:bold>,<jats:bold>3<\/jats:bold>) with appropriate secondary amines in the presence of carbonyldiimidazole (CDI) as a coupling reagent. The initial anticonvulsant screening was performed in mice intraperitoneally (<jats:italic>i.p<\/jats:italic>.) using the \u201cclassical\u201d maximal electroshock (MES) and subcutaneous pentylenetetrazole (<jats:italic>sc<\/jats:italic>PTZ) seizure models, whereas the acute neurological toxicity was determined applying the rotarod test. Additionally, several compounds were studied also in the 6\u2010Hz seizures recognized as the animal model of human pharmacoresistant epilepsy. In this series, compound<jats:bold>3q<\/jats:bold>displayed a broad spectrum of activity across the preclinical seizure models (ED<jats:sub>50<\/jats:sub>MES\u2009=\u200931.64\u2009mg\/kg; ED<jats:sub>50<\/jats:sub><jats:italic>sc<\/jats:italic>PTZ\u2009=\u200975.41\u2009mg\/kg, ED<jats:sub>50<\/jats:sub>6\u2010Hz (32\u2009mA)\u2009=\u200938.15\u2009mg\/kg). Consequently, compound<jats:bold>3q<\/jats:bold>revealed a wider spectrum of protection, higher activity or\/and a better safety profile than the commonly used antiepileptic drugs such as phenytoin, ethosuximide, valproic acid, or\/and levetiracetam. Notably, the<jats:italic>in vitro<\/jats:italic>studies showed that the most possible mechanism of action of<jats:bold>3q<\/jats:bold>may be connected to the interaction with neuronal voltage\u2010sensitive sodium channels (site 2). Other substances were active predominantly in the chemically induced seizures. The results of the current studies indicate that the presence of the pyrrolidine\u20102,5\u2010dione ring is important but not indispensable for anticonvulsant activity.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ardp.201600368","type":"journal-article","created":{"date-parts":[[2017,3,20]],"date-time":"2017-03-20T07:38:40Z","timestamp":1489995520000},"source":"Crossref","is-referenced-by-count":8,"title":["Synthesis and Anticonvulsant Properties of New 3,3\u2010Diphenyl\u20102,5\u2010dioxo\u2010pyrrolidin\u20101\u2010yl\u2010acetamides and 3,3\u2010Diphenyl\u2010propionamides"],"prefix":"10.1002","volume":"350","author":[{"given":"Jolanta","family":"Obniska","sequence":"first","affiliation":[{"name":"Department of Medicinal Chemistry Jagiellonian University Medical College Krak\u00f3w Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Rapacz","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy Department of Pharmacodynamics Jagiellonian University Medical College Krak\u00f3w Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabina","family":"Rybka","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry Jagiellonian University Medical College Krak\u00f3w Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ma\u0142gorzata","family":"G\u00f3ra","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry Jagiellonian University Medical College Krak\u00f3w Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3594-1241","authenticated-orcid":false,"given":"Pawe\u0142","family":"\u017bmudzki","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry Jagiellonian University Medical College Krak\u00f3w Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2103-371X","authenticated-orcid":false,"given":"Krzysztof","family":"Kami\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry Jagiellonian University Medical College Krak\u00f3w Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,3,20]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.64.12_suppl_3.S2"},{"key":"e_1_2_6_3_1","unstructured":"http:\/\/www.who.int\/mediacentre\/factsheets\/fs999\/en\/(WHO Epilepsy)."},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1004418"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1586\/ern.10.71"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2011.08.016"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-894X(03)00535-3"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ardp.201400152"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2015.07.017"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5b00578"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2016.02.026"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2015.12.027"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2016.04.066"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.3998\/ark.5550190.0004.502"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nurt.2006.11.009"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1358\/mf.2009.31.2.1338414"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2011.01.003"},{"key":"e_1_2_6_18_1","volume-title":"Antiepileptic Drugs","author":"White S. H.","year":"2002"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2005.12.041"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0920-1211(01)00302-3"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-014-0266-1"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nurt.2006.11.010"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1946.9.3.231"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2016.04.033"},{"key":"e_1_2_6_25_1","first-page":"81","volume":"3","author":"Boissier J. R.","year":"1960","journal-title":"Med. Exp"},{"key":"e_1_2_6_26_1","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/S0022-3565(25)05160-2","volume":"107","author":"Brown W. C.","year":"1953","journal-title":"J. Pharmacol. Exp. Ther"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12893"},{"key":"e_1_2_6_28_1","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0022-3565(25)03549-9","volume":"96","author":"Litchfield J. T.","year":"1949","journal-title":"J. Pharmacol. Exp. Ther"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.06-07-02064.1986"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.79.11.3656"}],"container-title":["Archiv der Pharmazie"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fardp.201600368","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ardp.201600368","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T04:52:20Z","timestamp":1750135940000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ardp.201600368"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,3,20]]},"references-count":29,"journal-issue":{"issue":"3-4","published-print":{"date-parts":[[2017,4]]}},"alternative-id":["10.1002\/ardp.201600368"],"URL":"https:\/\/doi.org\/10.1002\/ardp.201600368","archive":["Portico"],"relation":{},"ISSN":["0365-6233","1521-4184"],"issn-type":[{"value":"0365-6233","type":"print"},{"value":"1521-4184","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,3,20]]},"article-number":"1600368"}}