Syntheses of some 1-benzyl-2-(substituted)-4,5- diphenyl-1H-imidazole derivatives and investigation of their analgesic activities

SUMMARY In this study, twenty eight 1,2,4,5-tetrasubstituted-lH-imidazole derivatives were synthesized. Twenty two of the synthesized compounds are reported the first time. In the syntheses, benzoin derivative obtained using benzaldehyde was further oxidized to obtain benzil derivative. 2,4,5-Trisubstituted imidazole compounds were obtained as a result of the reaction of benzil derivatives with some substituted or nonsubstituted aldehyde derivatives. 1,2,4,5-Tetrasubstituted imidazole compounds were achieved by the treatment of purified imidazole compounds with benzyl chloride in the presence of sodium hydride. All of the synthesized compounds were purified using crystallization method and their structure elucidations were performed using spectral methods and elemantary analysis. Acute Lethal Toxicity (LD50) Test using Lorke method was applied to all compounds for toxicological and pharmacological studies. Derivatives, whose LD50 values were determined, then examined for their analgesic activities. Mechanical (Tail-Clip) and thermal (52.5 °C hot water) methods were used in these tests. At the end of the studies, analgesic activity was observed for some compounds in a series of 28 compounds; however, analgesic activity almost equivalent to morphine and statistically significant was determined for especially compound number 10. Some physicochemical parameters (steric, hydrophobic and electronic) of the compounds were determined to form the basis for the SAR studies which are planned as the continuation of this study. Steric, electronic and some hydrophobic parameter values were determined directly using table values, while RM hydrophobic parameter values were calculated using experimental data. Key words: Benzoin condensation, imidazole, trisubstituted imidazole, tetrasubstituted imidazole, analgesic activity