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Molecules 2015, 20(3), 3821-3840; doi:10.3390/molecules20033821

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

1
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
2
School of Pharmacy, University of Eastern Finland, Yliopistonranta 1, P.O. Box 1627, Kuopio FI-70211, Finland
3
Department of Pharmacology and Pharmacodynamics, Faculty of Pharmacy with Division of Medical Analytics, Medical University of Lublin, 4A Chodźki St., Lublin PL-20093, Poland
*
Authors to whom correspondence should be addressed.
Academic Editor: Derek J. McPhee
Received: 27 December 2014 / Revised: 21 January 2015 / Accepted: 9 February 2015 / Published: 26 February 2015
(This article belongs to the Section Medicinal Chemistry)
View Full-Text   |   Download PDF [2383 KB, uploaded 26 February 2015]   |  

Abstract

A series of 10 novel urea derivatives has been synthesized and evaluated for their central nervous system activity. Compounds 3a3h 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. View Full-Text
Keywords: central nervous system activity; opioid receptors; urea derivatives central nervous system activity; opioid receptors; urea derivatives
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Szacoń, E.; Rządkowska, M.; Kaczor, A.A.; Kędzierska, E.; Fidecka, S.; Matosiuk, D. 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. Molecules 2015, 20, 3821-3840.

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