Synthesis and biological activity of new О-(thietan-3-yl)-2-thiopyrimidine amide- and hydrazone derivatives

   Aim. Synthesis of new O-(thietan-3-yl)-2-thiopyrimidine amide- and hydrazone derivatives with antioxidant, antiaggregatory, and anticoagulant activity.

   Material and methods. New O-(thietan-3-yl)-2-thiopyrimidine amide derivatives were obtained by counter synthesis: the thietanylation of 6-methylpyrimidin-2-ylthioacetic acid amides and the interaction of ethyl 2-[6-methyl-4-(thietan-3-yloxy)pyrimidin-2-ylthio]acetate with aliphatic amines. New hydrazone derivatives of O-(thietan-3-yl)-2-thiopyrimidine were obtained by interaction 2-[6-methyl-4-(thietan-3-yloxy)pyrimidin-2-ylthio]acetohydrazide with aldehydes and ketones of various structures. The structure and purity of the synthesized compounds were confirmed by thin-layer chromatography, melting point determination, nuclear magnetic resonance and infrared spectra, as well as elemental analysis. The antioxidant properties of the compounds were evaluated in vitro in three model systems using a chemiluminescent express method. The effect on platelet aggregation was studied using the Born [1] aggregometry method on an «AT-02» aggregometer (RPC «Medtech», Russia). Anticoagulant activity was determined using generally accepted clotting tests on a Solar CGL 2110 turbidimetric hemocoagulometer (CJSC «SOLAR», Russia).

   Results. Methods for synthesizing new O-(thietan-3-yl)-2-thiopyrimidine amido- and hydrazone derivatives were developed, the structure of the obtained compounds was determined, studies of antioxidant, antiaggregation, and anticoagulation activity were conducted, and the most promising compounds were selected for further in-depth studies.

   Conclusions. New amido- and hydrazone derivatives of O-(thietan-3-yl)-2-thiopyrimidine with antioxidant, antiaggregation, and anticoagulation activity have been synthesized.

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