Synthesis of New 3-Morpholyl-Substituted 4-Aryl-2-Arylimino-2,3-Dihydrothiazole Derivatives and Their Anti-Inflammatory and Analgesic Activity

: pp. 532 - 542
Danylo Halytsky Lviv National Medical University
Danylo Halytsky Lviv National Medical University
National University of Pharmacy
National University of Pharmacy
National University of Pharmacy
Lviv National Medical University named after Danylo Halytskiy
I. Horbachevsky Ternopil National Medical University
Lviv Polytechnic National University
National University of Life and Environmental Sciences of Ukraine
Danylo Halytsky Lviv National Medical University
Danylo Halytsky Lviv National Medical University
Institute of Pharmacology and Toxicology, National Academy of Medical Sciences

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 bromoacetophenones 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 mechanism 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 compounds 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-inflammatory activity.

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