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. 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. Osteogenic agents are used for pathologies associated with impaired bone formation, complications of bone fractures, the use of implants and endoprostheses, and tumor lesions of bone tissue. High osteogenic activity in vivo on the model of experimental osteomyelitis, in vitro and in situ on mesenchymal stem cells was revealed for calcium chelidonate, which is a promising substance for the production of osteogenic drugs.Aim. Development of a method for obtaining the calcium chelidonate substance by chemical synthesis and methods of its standardization.Materials and methods. The synthesis of chelidonic acid was carried out on the basis of diethyloxalate; calcium chelidonate – using synthesized chelidonic acid and anhydrous calcium chloride. The structure of the substances was confirmed by optical spectral methods, mass spectrometry, elemental and X-ray structural analysis. The quantitative content was assessed using a liquid chromatograph. Statistical processing of the results of quantitative measurements was carried out in the STATISTICA 8,0 program.Results and discussion. As a result of the synthesis, chelidonic acid (4-oxo-4H-piran-2,6-dicarboxylic acid) was obtained, which is colorless or cream-tinged crystals. The structure of the resulting compound is confirmed by spectral characteristics and elemental analysis data. A method for obtaining the calcium chelidonate substance has been worked out, while the yield of the target product was 100 ± 5 %. By X-ray structural analysis, it was found that the synthesized compound is calcium chelidonate trihydrate [Ca(ChA)(H₂O)₃]_n with M.M. (C₇H₈O₉Ca) 276,15. Methods for establishing authenticity, purity and quantification of the substance have been developed. The amount of impurities in the resulting substance did not exceed 0.1 %, and the content of the main component ranged from 99,2 ± 0,20 to 100,4 ± 0,35 %.Conclusion. Due to the limited resource reserves and the complexity of the process of extracting chelidonic acid from plant raw materials, a method for the chemical synthesis of calcium chelidonate substance with osteogenic activity is proposed. The obtained results provide prospects for further research in the direction of the development and introduction of synthetic calcium chelidonate as a new osteogenic drug, provided that the specific biological activity is comparable to the natural analogue.

Introduction. One of the widely used specific anti-HER₂ (human epidermal growth factor receptor 2) MAb drugs is trastuzumab. Trastuzumab is highly effective for malignant HER₂ hyperexpression reduction, which results in HER₂ oncogenicity decrease. As any other biotherapeutics trastuzumab can cause immunological adverse reactions, e.g. immunogenicity or anti-drug antibodies (ADAs) production.Aim. The aim of this study was to develop and validate the analytical method for anti-trastuzumab antibodies determination in human blood serum.Materials and methods. The semi-quantitative anti-trastuzumab antibody determination was carried out by the ELISA method combined with ACE technique, using spectrophotometric detection in the visible range of the spectrum.Results and discussion. The developed method was validated for cut point, selectivity, sensitivity, "hook" effect, drug tolerance, precision and stability (short-term and long-term). To decrease the background noise from non-specific binding of sera components, the minimum required dilution value was determined at 10 % serum. The calculated values for screening cut point (normalization factor) and confirmatory cut point were 0.004 and 34.59 %, respectively. The sensitivity of the developed method was estimated at 99.5 ng/mL of anti-trastuzumab antibodies.Conclusion. The obtained results allow us to use the developed ACE ELISA method for the determination of anti-trastuzumab antibodies in human serum during trastuzumab safety clinical trials.

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. Vascular pathologies associated with thromboembolism are common complications and the leading cause of morbidity and mortality among patients of various nosological groups. Previously, we obtained water-soluble 2-hydroxy-4-oxo-4-R-2-butenoates of hetarylammonium, which exhibit a significant pharmacological effect on the blood coagulation system». A compound with a pronounced anticoagulant effect was found in various routes of administration. It was of interest to study various methods of confirming the authenticity of a potential anticoagulant.Aim. Development of methods for identification of a potential anticoagulant 2-hydroxy-4-oxo-(4-chlorophenyl)-2-butenoate of thiazolinammonium.Materials and methods. The studies were carried out on three series of the substance 2-hydroxy-4-oxo-(4-chlorophenyl)-2-butenoate of thiazolinammonium obtained in laboratory conditions. The melting point of BAS was measured by the capillary method according to GF XV OFS.1.2.1.0011 "Melting point". The solubility of the substance was determined in accordance with GF XV of the OFS.1.2.1.0005 "Solubility". The absorption spectra in the IR region were taken in accordance with GF XV of the OFS.1.2.1.1.0002 "Spectrophotometry in the middle infrared region". Absorption spectra in the UV region were taken in accordance with GF XV of the OFS.1.2.1.1.0003 "Spectrophotometry in the ultraviolet and visible regions". In carrying out qualitative reactions, reagents prepared in accordance with GF XV of the OFS were used.1.3.0001 "Reagents. Indicators".Results and discussion. A description of the substance has been carried out. The melting point and solubility of the compound were determined. Spectra in the IR and UV regions of the spectrum were taken. Methods were selected, and qualitative reactions of authenticity of a potential anticoagulant were carried out.Conclusion. The studied characteristics of the new BAS can be used in the standardization of the substance according to the indicators "Description", "Solubility", "Identification", "Melting point". These indicators characterize the physico-chemical properties of 2-hydroxy-4-oxo-(4-chlorophenyl)-2-butenoate of thiazolinammonium, and will be included in the draft regulatory documentation for the substance in the future.