{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:20:16Z","timestamp":1770596416144,"version":"3.49.0"},"reference-count":48,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2015,2,26]],"date-time":"2015-02-26T00:00:00Z","timestamp":1424908800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"publisher","award":["\u2018\u2018The equipment of innovative laboratories doing research on new medicines used in the therapy of civilization and neoplastic diseases\u2019\u2019 within the Operational Program Development of Eastern Poland 2007\u20132013, Priority Axis I modern Economy, operations I.3"],"award-info":[{"award-number":["\u2018\u2018The equipment of innovative laboratories doing research on new medicines used in the therapy of civilization and neoplastic diseases\u2019\u2019 within the Operational Program Development of Eastern Poland 2007\u20132013, Priority Axis I modern Economy, operations I.3"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"publisher","award":["Marie Curie fellowship for AAK"],"award-info":[{"award-number":["Marie Curie fellowship for AAK"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013923","name":"CSC","doi-asserted-by":"publisher","award":["1500"],"award-info":[{"award-number":["1500"]}],"id":[{"id":"10.13039\/501100013923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013327","name":"ICM","doi-asserted-by":"publisher","award":["G30-18"],"award-info":[{"award-number":["G30-18"]}],"id":[{"id":"10.13039\/100013327","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>A series of 10 novel urea derivatives has been synthesized and evaluated for their central nervous system activity. Compounds 3a\u20133h were prepared in the reaction between the respective 1-alkyl-4-aryl-4,5-dihydro-1H-imidazol-2-amines 1a and 1b and appropriate benzyl-, phenethyl-isocyanate or ethyl 4-isocyanatobenzoate and ethyl isocyanatoacetate 2 in dichloromethane. Derivatives 4c and 4g resulted from the conversion of 3c and 3g into the respective amides due to action of an aqueous ammonia solution. The results obtained in this study, based on literature data suggest a possible involvement of serotonin system and\/or the opioid system in the effects of tested compounds, and especially in the effect of compound 3h. The best activity of compound 3h may be primarily attributed to its favourable ADMET properties, i.e., higher lipophilicity (related to lower polar surface area and greater molecular surface, volume and mass than for other compounds) and good blood-brain permeation. This compound has also the greatest polarizability and ovality. The HOMO and LUMO energies do not seem to be directly related to activity.<\/jats:p>","DOI":"10.3390\/molecules20033821","type":"journal-article","created":{"date-parts":[[2015,2,26]],"date-time":"2015-02-26T10:07:43Z","timestamp":1424945263000},"page":"3821-3840","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Synthesis, Central Nervous System Activity and Structure-Activity Relationships of Novel 1-(1-Alkyl-4-aryl-4,5-dihydro-1H-imidazo)-3-substituted Urea Derivatives"],"prefix":"10.3390","volume":"20","author":[{"given":"El\u017cbieta","family":"Szaco\u0144","sequence":"first","affiliation":[{"name":"Department of Synthesis and Chemical Technology of Pharmaceutical Substances with Computer Modeling Lab, Faculty of Pharmacy with Division of Medical Analytics, Medical University of Lublin, 4a Chod\u017aki St., Lublin PL-20093, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marzena","family":"Rz\u0105dkowska","sequence":"additional","affiliation":[{"name":"Department of Synthesis and Chemical Technology of Pharmaceutical Substances with Computer Modeling Lab, Faculty of Pharmacy with Division of Medical Analytics, Medical University of Lublin, 4a Chod\u017aki St., Lublin PL-20093, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agnieszka","family":"Kaczor","sequence":"additional","affiliation":[{"name":"Department of Synthesis and Chemical Technology of Pharmaceutical Substances with Computer Modeling Lab, Faculty of Pharmacy with Division of Medical Analytics, Medical University of Lublin, 4a Chod\u017aki St., Lublin PL-20093, Poland"},{"name":"School of Pharmacy, University of Eastern Finland, Yliopistonranta 1, P.O. Box 1627, Kuopio FI-70211, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ewa","family":"K\u0119dzierska","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacodynamics, Faculty of Pharmacy with Division of Medical Analytics, Medical University of Lublin, 4A Chod\u017aki St., Lublin PL-20093, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylwia","family":"Fidecka","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacodynamics, Faculty of Pharmacy with Division of Medical Analytics, Medical University of Lublin, 4A Chod\u017aki St., Lublin PL-20093, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dariusz","family":"Matosiuk","sequence":"additional","affiliation":[{"name":"Department of Synthesis and Chemical Technology of Pharmaceutical Substances with Computer Modeling Lab, Faculty of Pharmacy with Division of Medical Analytics, Medical University of Lublin, 4a Chod\u017aki St., Lublin PL-20093, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2015,2,26]]},"reference":[{"key":"ref_1","first-page":"208","article-title":"Availability and utilization of opioids for pain management: Global issues","volume":"14","author":"Manjiani","year":"2014","journal-title":"Ochsner. 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