SYNTHESIS AND ANTIDEPRESSANT ACTIVITY OF 2-BROMO-1-(THIETAN-3-YL) IMIDAZOLE-4, 5-DICARBOXYLIC ACID DERIVATIVES
Objective: Synthesis of the salts and diylidenehydrazidÐµs of 2-bromo-1-(thietan-3-yl) imidazole-4,5-dicarboxylic acid to evaluate the antidepressant activities.
Methods: The structures of the synthesised compounds were confirmed by elemental analysis and 1Ð NMR spectral data. The melting points of the compounds were determined on a Stuart SMP30 apparatus. The X-ray diffraction data for compound IIc were obtained at room temperature on a Xcalibur Gemini Ð•os. The antidepressant activity was investigated in the tail suspension and forced swimming tests. The locomotor activity and anxiety were studied in the open field test.
Results: All synthesised compounds showed antidepressant activity after single intraperitoneal injection to male mice at doses equimolar to 10 mg/kg of imipramine. One of the compounds, 2-bromo-1-(thietan-3-yl) imidazole-4,5-dicarboxylic acid di[(4-hydroxy-3-methoxyphenyl) methylidenehydrazide], reduced the anxiety and decreased the locomotor activity at statistically significant levels. Other compounds did not have sedative and/or stimulating effects.
Conclusion: Among the synthesised 2-bromo-1-(thietan-3-yl) imidazole-4,5-dicarboxylic acid derivatives, compounds with marked antidepressant activity were identified. An obvious advantage of these products is low toxicity.
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