Synthesis and Antidepressant Activity of Thietane-Containing 4-(2-oxo-2-phenylethyl)-1H-1,2,4-triazol-4-ium Bromides

Thietane-containing 4-(2-oxo-2-phenylethyl)-1H-1,2,4-triazol-4-ium bromides were synthesized by quaternization of thietanyltriazoles with phenacyl bromides. The starting thietanyltriazoles were obtained by the reaction of 1,2,4-triazoles and 2-chloromethylthiirane followed by oxidation of 1-(thietan-3-yl)-1,2,4-triazole to 1-(1-oxidotheitan-3-yl)-1,2,4-triazole and 1-(1,1-dioxidothietan-3-yl)-1,2,4-triazole. The structures of the synthesized compounds were confirmed by IR, PMR, and C-13 and N-15 NMR spectroscopy. An in vivo study of the antidepressant activity revealed the promising compound 1-(1,1-dioxidothietan-3-yl)-4-(2-oxo-2-phenylethyl)-1H-1,2,4-triazol-4-ium bromide (IXa), which statistically significantly reduced the duration of immobilization in the forced swimming test by 44% as compared to the control group. Compound IXa is a low-toxic substance (class 4 toxicity) with a high bioavailability predicted according to in silico calculations.