Introduction.New potential biologically active compounds with different pharmacological activities were found among pyrimidine derivatives. Simple and available synthesis of tetrahydropyrimidine-5-carboxamides was developed in Perm State Pharmaceutical Academy. Products of this reaction previously shown high analgesic and anti-inflammatory activities.Aim.To get previously unknown functionalized pyrimidines and to study their analgesic, anti-inflammatory and antipyretic activities.Materials and methods.11 compoundsN,6-diaryl-4-methyl-2-thioxo-1,2,3,6-tetrahydropyrimidine-5-carboxamides are objects of research. Their structure has been confirmed by spectroscopy methods. The biological activities were carried out by recommended methods for preclinical study of new pharmacological substances.Results and discussion.This paper presents the results of preclinical tests of the obtained compounds.Conclusion.Some compounds demonstrated high analgesic, anti-inflammatory and antipyretic activities and could be recommend for further study as perspective non-steroidal drugs.

Introduction. Antioxydant activity, membrane stabilizing and cytoprotective effect of dihydropyrimidin analoges are widely described in various literary sources. One of the importantant mechanisms of action of antioxidants is their antihypoxic activity. It is the ability to increase tissue resistance to hypoxia. The search for drugs to increase the body's resistance under hypoxic conditions is an actual task in experimental and clinical pharmacology.Aim. Study of the antihypoxic activity of new S-analogs of dihydropyrimidin-2-ones and their condensed derivatives in various models of hypoxia.Materials and methods. 13 compounds S-analogs of dihydropyrimidin-2-ones and their condensed derivatives are objects of research. Their structure has been confirmed by spectroscopy methods. The antihypoxic activity was carried out by recommended methods for preclinical study of new pharmacological substances.Results and discussion. This paper presents the results of testing the obtained compounds of different structures on three models of hypoxia. The activity of a number of condensed tricyclic derivatives of dihydropyrimidine-2-thiones was studied in more detail using a model of acute normobaric hypoxia with hypercapnia.Conclusion. The compounds did not demonstrate high antihypoxic activity; some «structure-property» patterns were revealed.

Introduction. Environmental monitoring is an important area of modern scientific research. This is due to the anthropogenic impact on the environment, which often negatively affects the diversity of the Russian medicinal flora. The use of modern instrumental analytical methods of medicinal plant raw materials is relevant due to the intensive development of science. The content of heavy metals, the elemental composition and the level of background radiation are important characteristics of ecological purity and safety of medicinal plant raw materials. These characteristics are of interest for assessing the possibility of harvesting and using medicinal plants at localization. The generally accepted instructions for harvesting were used.Aim. Investigation of the possibilities of using X-ray fluorescence and radiation methods for environmental monitoring of medicinal plant raw materials.Materials and methods. The research object was Achilleae millefolii herba. The harvestment of plant raw materials was carried out in the Bardymsky, Chernushinsky, Uinsky, Kishertsky, Oktyabrsky, Suksunsky, Ordinsky, Sivinsky districts of the Perm Region in the summer in 2022–2023. The X-ray fluorescence analyzer (XFA) ARL QUANT'X EDXRF was used to determine heavy metals and assess the elemental composition of plants. The analysis was carried out according to the methodology that was developed by scientists of the Pharmacognosy Department at the Perm State Pharmaceutical Academy. The radiation background in raw materials was assessed by using a special dosimeter RADEX RD1503.Results and discussion. As a result, it was found that harvesting of Achilleae millefolii herba is possible in the Perm Region studied areas. Bardymsky, Uinsky, Kishertsky, Ordinsky, Chernushinsky districts are the most recommended for harvesting plant raw materials. Samples from these areas are ecological purity and safe for use as medicinal raw materials and have a diverse elemental composition. The content of heavy metals does not exceed the maximum permissible concentrations according to the regulatory documentation requirements. The background radiation level does not exceed the threshold value compared to other areas in the Russian Federation.Conclusion. X-ray fluorescence analysis is a suitable and reliable analytical method for determining elements in plant raw materials. XFA is a multi-element express method that allows analyzing a sample with minimal sample preparation. The advantages of the method are good reproducibility, high sensitivity, and efficiency. Research continues.

Introduction. Molecular modeling methods are very popular in the scientific community at the present time. The value of the pharmacological action depends on the affinity of the substance to the biological target. Molecular docking makes it possible to assess the degree of affinity of the studied compound with the active center of the molecular target. The enzyme cyclooxygenase (COX) plays a key role in the cascade of synthesis of proinflammatory cytokines and, as a consequence, in pain.Aim. To identify the dependence "structure – analgesic activity" using the method of molecular docking for cyclooxygenase type 1 and type 2 in the series of 5-N-arylaminocarbonyl-6-(get)aryl-4-methyl-1,2,3,6-tetrahydropyrimidine-2-thions.Materials and methods. 19 compounds 5-N-arylaminocarbonyl-6-(get)aryl-4-methyl-1,2,3,6-tetrahydropyrimidine-2-thions are objects of research The study of the interaction of tetrahydropyridine derivatives with COX 1 and 2 was carried out by the method of molecular docking by the AutoDock 4 program using scoring functions.Results and discussion. Molecular docking of 5-N-arylaminocarbonyl-6-(get)aryl-4-methyl-1,2,3,6-tetrahydropyrimidine-2-thions (I–XIX) with COX 1 and 2 is described. Quantitative studies of the "structure – analgesic activity" in the studied series of compounds of the dependence of experimental values of analgesic activity (АА_ex.) on scoring functions (Be_COX1, Ki_COX1, Be_COX2, Ki_COX2) and physico-chemical descriptors (log P_pred., рКа_pred., рКv_pred.) were performed. By checking on an independent sample of 5 compounds, equation No. 3 (АА_pred. 3 = 32,6215 – 4,4894 × Be_cox1 + 0,0066 × Ki_cox1 + 3,6032 × log P_pred. (R = 0,854, F = 9,01, S = 7,73, Q²_LOO = 0,53) was found, with a high value of the correlation coefficient of the predicted values АА_ex. with experimental values (R_pred. = 0,878) and a minimum forecast error (S_pred. = 6,74).Conclusion. The "structure-activity" models for predicting analgesic activity in a series of 5-N-arylaminocarbonyl-6-(get)aryl-4-methyl-1,2,3,6-tetrahydropyrimidine-2-thions are obtained. The result of the prediction of biological activity is confirmed by the values of the correlation coefficient (R) obtained when testing models on independent samples.

Introduction. The use of anticoagulants is relevant in therapeutic, cardiological, neurological practice, geriatrics, obstetrics and gynecology, as well as in complications associated with COVID-19 infection and vaccination. In-depth studies of additional pleiotropic effects of existing anticoagulants are being conducted. The anti-inflammatory effect of heparins and direct oral anticoagulants was found. Special emphasis is placed on the existing close relationship between coagulation and inflammatory processes. The interaction of anticoagulants with nonsteroidal anti-inflammatory drugs when taken together is actively discussed. The combination of anticoagulant and anti-inflammatory action in one chemical molecule can solve the problem of polypragmasia.Aim. To study the anti-inflammatory activity of promising 2-hydroxy-4-oxo-4-R-2-butenoates of heterylammonium, which have an effect on the blood clotting system.Materials and methods. For further study of anti-inflammatory activity, 2-hydroxy-4-oxo-4-R-2-butenoates of heterylammonium, which have an effect on the blood clotting system, were selected. The anti-inflammatory effect was studied on a model of acute inflammatory edema in mongrel rats of both sexes weighing 180–250 g. The studied compounds were administered intragastrically. Diclofenac sodium and nimesulide substances administered similarly were used as comparison drugs. Acute toxicity of substances that showed activity was studied on white nonlinear mice of both sexes weighing 18–22 g with the definition of LD₅₀.Results and discussion. All the studied 2-hydroxy-4-oxo-4-R-2-butenoates of heterylammonium have anti-inflammatory effects of varying severity. Data on the study of acute toxicity during intragastric administration, allow us to attribute the studied compounds to the 4.5 class of the hazard classification of chemical products.Conclusion. The anti-inflammatory activity of 14 2-hydroxy-4-oxo-4-R2-butenoates of heterylammonium has been studied. Five butanoate have an effect lower than comparison drugs, eight compounds are comparable to the effect of reference drugs, one compound is superior to nimesulide. The studied compounds can be assigned to class 4,5 of the hazard classification of chemical products. Medicinal candidates have been selected for further pharmacological, toxicological and technological study.