Synthesis and pharmacological activity of new carbonyl derivatives of 1-aryl-2-iminoimidazolidine. Part 1. Synthesis and pharmacological activity of chain derivatives of 1-aryl-2-iminoimidazolidine containing urea moiety.
The synthesis and physicochemical properties of new carbonyl derivatives of 1-aryl-2-iminoimidazolidine are presented. Isomeric 1-(1-arylimidazolidine-2-ylidene)-3-arylureas (series A) and 1-aryl-2-imine-3-arylaminocarbonylimidazolidines (series B) were obtained after the condensation reaction of 1-aryl-2-iminoimidazolidines and arylisocyanates. 1-Aryl-2-iminoimidazolidines were synthesised in a two-step reaction from the respective anilines. The molecular structure of 1-(1-phenylimidazolidine-2-ylidene)-3-(4-chlorophenyl)urea (A2) has been determined by X-ray crystallography. The representatives of both investigated series were evaluated in behavioural animal tests. They exhibited significant, especially analgesic, activity on the animal central nervous system (CNS). They displayed substantial effect on the serotonine and catecholamine neurotransmission as well, at very low toxicity (LD(50) over 2000 mg kg(-1) i.p.). In the binding affinity tests they exhibited moderate affinity (on the micromolar level) toward opioid (mu) and serotonine (5HT(2)) receptors. The derivatives of series A had moderate affinity toward benzodiazepine (BZD) receptor as well. Distinctive differences observed in their activity spectra can be connected with the presence of particular structural features such as relative orientation of the two aromatic rings and the carbonyl moiety.
Matosiuk
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Department of Synthesis and Technology of Drugs, Medical University, Staszica 6, PL-20-081, Lublin, Poland. darek@eskulap.am.lublin.pl
Fidecka
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Antkiewicz-Michaluk
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Dybała
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Kozioł
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D000700:Analgesics / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002490:Central Nervous System / Q000187:drug effects; D002491:Central Nervous System Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray / Q000379:methods; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D051379:Mice; D011485:Protein Binding; D011963:Receptors, GABA-A / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism; D014508:Urea / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*
D000700:Analgesics; D002491:Central Nervous System Agents; D007093:Imidazoles; D011963:Receptors, GABA-A; D017450:Receptors, Opioid, mu; D011985:Receptors, Serotonin; D014508:Urea; C006048:imidazolidinyl urea