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In accordance with the basic principle proposed by Lipinski's rule, the probable bioavailabilities of the <jats:bold>F1<\/jats:bold>\u2013<jats:bold>F4<\/jats:bold> phthalimides were assessed. The obtained values indicate good absorption after oral administration and the ability to cross the blood\u2013brain barrier. The four compounds <jats:bold>F1<\/jats:bold>\u2013<jats:bold>F4<\/jats:bold> differing in the type of pharmacophore in the phenyl group of the 2\u2010hydroxy\u20103\u2010(4\u2010aryl\u20101\u2010piperazinyl)propyl on the imide nitrogen atom (R, <jats:bold>F1<\/jats:bold>\u2013<jats:bold>F3<\/jats:bold>) and the 4\u2010benzhydryl analog (<jats:bold>F4<\/jats:bold>) were selected for in vitro and in vivo studies. Based on the in vitro studies, the effects of compounds <jats:bold>F1<\/jats:bold>\u2013<jats:bold>F4<\/jats:bold> on cell viability\/proliferation and COX\u20102 levels were evaluated. Moreover, using in vivo methods, the compounds were tested for antinociceptive activity in models of acute pain (the writhing and the hot\u2010plate tests) in mice. Their influence on the motor coordination effect and locomotor activity was also tested. The obtained results revealed that the compounds <jats:bold>F1<\/jats:bold>\u2013<jats:bold>F4<\/jats:bold> strongly suppress the pain of peripheral origin and to a lesser extent (<jats:bold>F1<\/jats:bold>\u2013<jats:bold>F3<\/jats:bold>) pain of central\/supraspinal origin. In the in vitro studies, <jats:bold>F1<\/jats:bold>\u2013<jats:bold>F4<\/jats:bold> reduced the COX\u20102 level in lipopolysaccharide\u2010activated RAW 264.7 cells, which suggests their anti\u2010inflammatory activity.<\/jats:p>","DOI":"10.1002\/ardp.202100423","type":"journal-article","created":{"date-parts":[[2022,4,9]],"date-time":"2022-04-09T09:24:44Z","timestamp":1649496284000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Synthesis and antinociceptive activity of four 1<i>H<\/i>\u2010isoindolo\u20101,3(2<i>H<\/i>)\u2010diones"],"prefix":"10.1002","volume":"355","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6377-5749","authenticated-orcid":false,"given":"Anna","family":"Dziubina","sequence":"first","affiliation":[{"name":"Department of Pharmacodynamics Faculty of Pharmacy, Jagiellonian University Medical College  Krak\u00f3w Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6543-4753","authenticated-orcid":false,"given":"Dominika","family":"Szkatu\u0142a","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry Wroc\u0142aw Medical University  Wroc\u0142aw Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3501-8350","authenticated-orcid":false,"given":"Joanna","family":"Gdula\u2010Argasi\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Pharmacobiology Faculty of Pharmacy, Jagiellonian University Medical College  Krakow Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4670-1665","authenticated-orcid":false,"given":"Jacek","family":"Sapa","sequence":"additional","affiliation":[{"name":"Department of Pharmacodynamics Faculty of Pharmacy, Jagiellonian University Medical College  Krak\u00f3w Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,4,9]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0896(02)00152-9"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharep.2017.01.033"},{"key":"e_1_2_7_4_1","first-page":"1","volume":"660","author":"Antunesa R.","year":"2003","journal-title":"Structure"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1248\/cpb.52.1021"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2004.06.026"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1248\/cpb.52.498"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/md15010007"},{"key":"e_1_2_7_9_1","first-page":"133","volume":"56","author":"\u015aladowska H.","year":"2001","journal-title":"Pharmazie"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-827X(02)01302-2"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-827X(03)00062-4"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.farmac.2004.08.011"},{"key":"e_1_2_7_13_1","first-page":"245","volume":"63","author":"\u015aladowska H.","year":"2006","journal-title":"Acta Pol. 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