title: Synthesis and Pharmacological Evaluation of Novel 1-(1,4-Alkylaryldisubstituted-4,5-dihydro-1H-imidazo)-3-substituted Urea Derivatives.
abstract: Novel 1-(1,4-alkylaryldisubstituted-4,5-dihydro-1H-imidazo)-3-substituted urea derivatives have been synthesized and evaluated for their central nervous system activity. Compounds 3a-m were prepared in the reaction between the respective 1-alkyl-4-aryl-4,5-dihydro-1H-imidazol-2-amines 1a-c and appropriate isocyanates 2 in dichloromethane. The compounds were subjected to in silico ADMET studies in order to select best candidates for in vivo experiments. The effects of the compounds on the spontaneous locomotor activity and amphetamine-evoked hyperactivity were estimated. Analgesic activity, without or in the presence of naloxone, was assessed in the writhing test. The tendency to change the HTR, evoked by l-5-HTP and the involvement in alteration in body temperature in mice was studied. Additionally, to check possible occurrence of drug-induced changes in the muscle relaxant activity of mice, which may have contributed to their behaviour in other tests, the rota-rod and chimney tests were performed. The new urea derivatives exerted significant activities in the performed pharmacological tests, although the presented results show a preliminary estimation, and thus, need to be extended for identification and understanding the complete pharmacological profile of the examined compounds.
authors.affiliation: 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 Chodźki St., Lublin PL-20093, Poland. elzbieta.szacon@umlub.pl.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Szacoń
authors.affiliation: 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 Chodźki St., Lublin PL-20093, Poland. marzena.rzadkowska@umlub.pl.
authors.forename: Marzena
authors.initials: M
authors.lastname: Rządkowska
authors.affiliation: 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 Chodźki St., Lublin PL-20093, Poland. agnieszka.kaczor@umlub.pl.|School of Pharmacy, University of Eastern Finland, Yliopistonranta 1, P.O. Box 1627, Kuopio FI-70211, Finland. agnieszka.kaczor@umlub.pl.
authors.forename: Agnieszka A
authors.initials: AA
authors.lastname: Kaczor
authors.affiliation: Department of Pharmacology and Pharmacodynamics, Faculty of Pharmacy with Division of Medical Analytics, Medical University of Lublin, 4A Chodźki St., Lublin PL-20093, Poland. ewa.kedzierska@umlub.pl.
authors.forename: Ewa
authors.initials: E
authors.lastname: Kędzierska
authors.affiliation: Department of Pharmacology and Pharmacodynamics, Faculty of Pharmacy with Division of Medical Analytics, Medical University of Lublin, 4A Chodźki St., Lublin PL-20093, Poland. jolanta.orzelska@umlub.pl.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Orzelska-Górka
authors.affiliation: Department of Pharmacology and Pharmacodynamics, Faculty of Pharmacy with Division of Medical Analytics, Medical University of Lublin, 4A Chodźki St., Lublin PL-20093, Poland. sylwia.fidecka@umlub.pl.
authors.forename: Sylwia
authors.initials: S
authors.lastname: Fidecka
authors.affiliation: 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 Chodźki St., Lublin PL-20093, Poland. dariusz.matosiuk@umlub.pl.
authors.forename: Dariusz
authors.initials: D
authors.lastname: Matosiuk
mesh_terms: D018712:Analgesics, Non-Narcotic / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D015195:Drug Design; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051379:Mice; D011957:Receptors, Opioid / Q000187:drug effects; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D018712:Analgesics, Non-Narcotic; D007093:Imidazoles; D011957:Receptors, Opioid; D014508:Urea
keywords: 1-alkyl-4-aryl-4,5-dihydro-1H-imidazo-2-amines; antinociceptive compounds; central nervous system (CNS) activity; in silico ADMET studies