Pyrimidine base derivatives, having a wide spectrum of pharmacological activity along with low toxicity, are used as active ingredients of many drugs. Thus, many compounds of the uracil series have antitumor, anti-inflammatory, antiviral, immunomodulatory effects, in connection with which the synthesis of new biologically active derivatives of the pyrimidine series is relevant. It is known that the mechanism of hepatotoxicity of chemical compounds is largely associated with the activation of lipid peroxidation, therefore, uracil derivatives containing a proton-donor group in position C5 were chosen as objects of study, which significantly increases the antioxidant properties of the compound. For the synthesis of uracil derivatives at N¹, N³ positions, modification of 5-hydroxy- and 5-amino-6-methyluracils with pre-protected C5 functional groups with various alkyl substituents was carried out. The method of preliminary etching of cells with the hepatotoxicant tetrachloromethane and their treatment with the studied compounds was selected as a study of hepatoprotective activity. The introduction of various alkyl substituents at the N¹, N³ positions of 5-hydroxy and 5-amino-6-methyluracils leads to an increase in the solubility of these compounds, the hepatoprotective activity of the synthesized compounds was revealed. New di- and monoalkyl derivatives of 5-hydroxy- and 5-amino-6-methyluracil were obtained, their hepatoprotective activity was tested in vitro. According to the test results, five of the new 20 synthesized compounds promote cell survival when pre-treated with tetrachloromethane.