Synthesis of new 3-morpholyl-substituted 4-aryl-2-arylimino-2,3-dihydrothiazole derivatives and their anti-inflammatory and analgesic activity

Abstract

New 4-aryl-3-(morpholin-4-yl)-2-arylimino-2,3- dihydrothiazole derivatives 1.1-1.16 were obtained using the Hantzsch reaction by condensation of N-(morpholin-4- yl)-N'-arylthioureas with the corresponding α-bromoace- tophenones in alcohols. Synthesized hydrobromides 1.1-1.8 were formed as crystalline precipitates during the boiling of the reaction mixture. Bases 1.9-1.16 were obtained by neutralizing the corresponding hydrobromides with NH4OH solution. It has been proposed a possible mecha- nism of the reaction that is based on the study of the structure of the synthesized compounds. The structures of the synthesized compounds were confirmed by 1H NMR spectroscopy with its special techniques (NOESY and ROESY experiments). It has been shown the formation of the isomer 4-(4'-chlorophenyl)-3-(morpholin-4-yl)-2-(4'- chlorophenylamino)-2.3-dihydrothiazole on the basis of compound 1.14. Pharmacological screening of synthesized derivatives of 4-aryl-2-arylimino-2,3-dihydrothiazole com- pounds revealed the analgesic effect in the model of visceral pain caused by the introduction of acetic acid to white mice. The anti-inflammatory effect of the synthesized compounds was evaluated in vivo by reducing limb edema in rats with carrageenan-induced inflammation. Thus, the synthesized compounds have analgesic and anti-inflam- matory activity.