E.E. Klen, I.L. Nikitina, F.A. Khaliullin, G.F. Ischakova, E.K. Alekhin, О.A. Ivanova

The 1,2,4-triazole compounds are considered as interesting heterocycles since they possess important pharmacological activities. This fact allows us to hope for the developing bioactive compounds among 1,2,4-triazoles containing thietane moiety and, in this study, to synthesize a series of new 3,5-disubstituted 1-(thietanyl-3)-1,2,4-triazoles. We first synthesized nine new 5-aminoderivatives of 3-bromo-1-(thietanyl-3)-1,2,4-triazole (IIа-и) by the reactions of 3,5-dibromo-1-(thietanyl-3)-1,2,4-tria¬zole (I) with excess of amines in butanole with 25 - 98% yield. 5-Alkoxy-3-bromo-1-(thietanyl-3)-1,2,4-triazoles (IIIа-д) were obtained by the reactions of 3,5-dibromo-1-(thietanyl-3)-1,2,4-tria¬zole (I) with sodium alkoxide in appropriate alcohol. The structure of new compounds was confirmed by NMR, IR spectra and elemental analysis. The spectral data were consisted with the proposed structures. In the NMR spectra additional signals due to substitute at C5 position with corresponding chemical shifts were observed. The hexobarbital sleeping test was carried out and the quantity of cytochrome P450 and b5 in the liver were determined to study the effects of thietanyl-1,2,4-triazoles on activity of the liver monooxygenase system. Among the compounds is tested, IIа, IIи and IIв, exhibit insignificant inhibitive effect on the liver monooxygenase system. One of tested compounds is 3-bromo-5-pyperidino-1-(thietanyl-3)-1,2,4-triazole IIз, it exhibits statistically reliable stimulating effect on the liver monooxygenase system.