Introduction. Irrational use of antimicrobial drugs, chemical and biological agents leads to the emergence and spread of resistance in microorgan-isms. Therefore, there is an increasing need for the search and development of new antimicrobial compounds. Dihydroxanthone derivatives, which have a wide spectrum of action, are one of the promising groups of antimicrobial substances. New derivatives of 4,4a-dihydroxanthone were obtained at the St. Petersburg State Chemical and Pharmaceutical University (SPCFU) at the Department of Organic Chemistry. Synthetic 4,4a-dihydroxanthones are structurally similar to antimicrobial xanthones of natural origin – fomalevones A and C. Therefore, 4,4a-dihydroxanthones are promising compounds for the creation of new antimicrobial substances. Purpose of the study. To establish the relationship between the chemical structure of the synthesized dihydroxanthones and their antimicrobial ac-tivity and to standardize the active compound. Materials and methods. 20 new derivatives of 4,4a-dihydroxanthone were synthesized. The structure and identity of the compounds was estab-lished using physical and chemical methods of analysis. The antimicrobial activity of these derivatives was studied by double serial dilution method. Quality standards for the most promising compound 5-bromo-7-chloro-4,4-dimethyl-9-oxo-4,4a-dihydroxanthone (a17) were developed. Results. In preliminary studies, we found that 4,4a-dihydroxanthones synthesized in SPCFU have a pronounced effect against gram-positive bacteria. It was found, that the antibacterial activity of 4,4a-dihydroxanthone derivatives depended on their structure. The presence of substituents with acceptor properties led to an increase in activity, while donor substituents reduced the antimicrobial effect of the compounds. 5-Bromo-7-chloro-4,4-dimethyl-9-oxo-4,4a-dihydroxanthone (a17) turned out to be the most active compound, and we carried out its standardization for some indicators. Conclusions. During the study of the antimicrobial activity of the synthesized dihydroxanthones, it was found that they are active against gram-positive bacteria. The antibacterial activity of 4,4a-dihydroxanthone derivatives depends on their structure. Among them, the most active compound was identified – leader a17, which has a pronounced antistaphylococcal effect. Its standardization has been carried out for some indicators.

Introduction. The development of methods for analyzing new potentially active pharmaceutical substances is an important part of substance standardization. An integrated approach to confirming the structure of a substance is especially important when the substance may exist in different tautomeric forms, since the properties of the substance may change depending on tautomerism, affecting, among other things, the pharmacological activity.Aim. The aim of our study was to determine the tautomeric composition of the potential active pharmaceutical substance 5-butyl-6-hydroxy-2,3-diphenylpyrimidin-4(3H)-one in solid state and solution for the subsequent development of its dosage form and determination of bioavailability.Material and methods. The object of the study was the substance 5-butyl-6-hydroxy-2,3-diphenylpyrimidin-4(3H)-one. Spectra were taken to confirm the structure: infrared on a PerkinElmer Spectrum 3 device (PerkinElmer Inc., USA) in the frequency range from 4000 to 400 cm–1, nuclear magnetic resonance 1H and 13C on a pulsed broadband spectrometer Bruker AM-500 (400 and 100 MHz) (Bruker, Germany) in DMSO-d6 solvent, ultraviolet using SF-2000 (LLC "OKB Spektr", Russia) in the wavelength range of 250–400 nm, and high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) was also carried out.Results and discussion. A feature of pyrimidine hydroxy derivatives is the presence of tautomeric forms, which can affect both the physicochemical properties of the substance and its pharmacological activity. The study found that in the solid state, 5-butyl-6-hydroxy-2,3-diphenylpyrimidin-4(3H)-one is in equilibrium between the diketo form and the enol form, and when the substance is dissolved in dimethyl sulfoxide (DMSO), the enol form is predominant. The purity was confirmed by HPLC-MS/MS.Conclusion. The structure of 5-butyl-6-hydroxy-2,3-diphenylpyrimidin-4(3H)-one was confirmed by IR and NMR spectroscopy. UV spectra were obtained, and HPLC-MS/MS was performed to exclude possible absorption of ultraviolet radiation by impurities.

Reactions of ethyl 3-(4-oxo-4H-chromen-3-yl)prop-2-enoates with 1,2-binucleophilic agents (hydrazine, phenylhydrazine, hydroxylamine) leads to the formation of some new pyrazole and isoxazole derivatives. The reactions proceed under mild conditions (ethanol, room temperature) to form the title products with high yields (71–99%).

O-Alkyl hydrazinecarbothioates, which are potential building blocks in the synthesis of heterocycles and antimicrobial agents, were obtained from primary alcohols in 38–89% yields by a one-pot method. The obtained compounds are characterized by thione-thiol tautomerism in a solution. An experimental screening for antibacterial and antifungal activity of hydrazinecarbothioates was performed, the highest activity was found against B. cereus and St. aureus strains.

The reaction of N-(2-methylpropenyl)pyrrolidine with 3-vinylchromones containing non-acidic electron-withdrawing groups (ester, nitrile) was studied. The conditions, that make it possible to manage the side [1,5] sigmatropic rearrangement, were found. As a result, new derivatives of 4,4a-dihydroxanthone containing ester and nitrile groups were obtained.

A procedure has been developed for the synthesis of 6,7-dihydroindazoles and 7,8-dihydroquinazolines by reaction of 3,4-dihydroxanthone derivatives with 1,2- and 1,3-binucleophiles (hydrazine, guanidine). The reaction occurred under mild conditions (methanol, 20-65°C) with high yields.

The reaction of (4-chlorobenzoyl)pyruvic acid methyl ester with a mixture of aromatic aldehyde and 4-aminobenzoic acid ethyl ester in glacial acetic acid afforded ethyl 4-[5-aryl-3-hydroxy-2-oxo-4-(4-chlorobenzoyl)-2,5-dihydro-1H-pyrrol-1-yl]benzoates.

A procedure for the synthesis of 2-anilino-6-hydroxy-3-phenylpyrimidin-4(3H)-one (mafedine) without using alkali metal ethoxides has been developed and optimized. Mafedine-related compounds that can be formed as possible impurities have been prepared, and conditions for joint determination of these impurities by HPLC with spectrophotometric detection have been found. The structure of the mafedine decomposition product in solution has been identified by HPLC-ESI/MS.

The primary reference sample (RS) use is one of the conditions necessary for conducting pharmaceuticals appropriate quality control. Therefore, their development is an urgent problem for the pharmaceutical industry, especially for new biologically active compounds that can be further used as pharmaceuticals. The aim of the work is to develop a primary standard sample of new sodium 1,2-dipheny l-5-butyl-6-oxo-1,6-dihydropyrimidine-4-olate. This substance can be used in medical practice as an anti-inflammatory agent. Primary RS was obtained by additional purification of the additional pharmaceutical substance by threefold recrystallization of acetone. The work on its certification was the following: the structure was confirmed, such indicators as weight loss on drying, inorganic impurities (chlorides, sulphated ash, heavy metals), related impurities were determined. The main component quantitative content has been established using the material balance.

Introduction. The standard samples (SS) use is a necessary condition for the medicines' quality control implementation. Their development is an urgent problem for the pharmaceutical industry, especially for new biologically active compounds that can be further used as pharmaceuticals.Aim. This work aim is to establish the 5-butyl-1,2-diphenyl-6-oxo-1,6-dihydro pyrimidone-4-olate sodium quantitative content, for which anti-inflammatory and analgesic activity was previously proven, in a standard sample.Materials and methods. This work aim is to establish the 5-butyl-1,2-diphenyl-6-oxo-1,6-dihydro pyrimidone-4-olate sodium quantitative content, for which anti-inflammatory and analgesic activity was previously proven, in a standard sample. The main method for establishing a substance quantitative content in the SS is the material balance method. The water determination was carried out according to K. Fisher's method (semimicro method). Sulphated ash was determined according to the XIV edition Russian Federation State Pharmacopoeia General Pharmacopoeia Monograph "Sulphated ash". Related impurities and their content were assessed using the HPLC method on a Flexar liquid chromatograph equipped with a diode array detector (Perkin Elmer, USA). The residual solvents' determination was carried out by the headspace method using a gas chromatograph GC-2010Plus Shimadzu with a flame ionization detector. As an additional method for establishing the main component quantitative content, acidimetric titration with the equivalence point potentiometric indication was carried out.Results and discussion. The percentage was determined for the following indicators: water, residual organic solvents, related impurities, sulphated ash. Using the material balance method, it was found that the 5-butyl-1,2-diphenyl-6-oxo-1,6-dihydropyrimidin-4-olate sodium percentage in a standard sample is 96.01 ± 0.50 %. It was found by acidimetric titration that the 5-butyl-1,2-diphenyl-6-oxo 1,6-dihydropyrimidin- 4-olate sodium quantitative content in SS is 95.12 ± 0.02 %. The difference in the certified value can be explained by the fact that during titration, the SS aciform is released, which precipitates in an aqueous medium and contributes to a shift in the equilibrium and pH value. Consequently, the equivalence point is reached somewhat earlier. However, the data are practically comparable, but it is necessary to use the value obtained by the material balance method.Conclusion. A standard sample certification parameters were determined: water content, residual organic solvents, sulphated ash, related impurities. The main component quantitative content was determined using the material balance method and titrimetry (acidimetry with the equivalence point potentiometric indication).

A number of new pyrazole and pyrimidine derivatives containing an allylmorpholine fragment were obtained by reactions of chromone-containing allylmorpholines with 1,2- and 1,3-binucleophiles (hydrazine, guanidine, acetamidine). The syntheses were carried out under mild conditions (ethanol, room temperature), and the target products were isolated with high yields. The obtained compounds are of interest as potential cholinesterase inhibitors.

In order to predict the biological activity of the new derivatives of 4,4a-dihydroxanthone, the PASS (Prediction ofActivity Spectra for Substances) computer program was used. It allows predicting the biological activity spectrum of chemical compounds based on the analysis of structure-activity interrelation. Derivatives of 4,4a-dihydroxanthone were synthesized at the Department of Organic Chemistry of the Saint Petersburg State Chemical Pharmaceutical University. As a result of the screening, it was found that 4,4a-dihydroxanthones can exhibit antibacterial, antifungal, antitumor, and antiviral effects. Antimicrobial activity of the obtained compounds was studied against Gram-positive and Gram-negative bacteria, as well as fungi. Dihydroxanthones were shown to have an inhibitory effect on Gram-positive bacteria. Relationship between the structure of derivatives and their antimicrobial activity is established. The presence of electron-withdrawing substituents led to an increase in activity, and electron-donating substituents reduced the antibacterial effect of the compounds. The most active compound, 5-bromo-7-chloro-4,4a-dihydrox-anthone, was found to be active against certain clinical strains of staphylococci.

The reaction of carboxylic acid amides with malonyl chloride in acetonitrile or tetrahydrofuran without heating leads to the formation of previously unknown 2-substituted 5-hydroxypyrano[2,3-d][1,3]oxazines. The structure of the obtained compounds was established by high resolution mass spectrometry, NMR spectroscopy, and X-ray analysis.

The reaction of formylation by Vilsmeier - Haack was held. The effect of excess phosphorus oxychloride in the direction of the reaction. Optimal conditions were conducting formylation reaction to obtain a single compound with a high yield. The result of the reaction product mixture was conducted chromatographic separation on a column packed with silica gel 60 Silica.

A procedure has been developed and optimized for the synthesis of 3-{[4-methyl-3-(4-methylpiperazin-1-yl)]pent-1-en-1-yl}-4 H -chromen-4-ones (as dihydrochlorides) by an unusual version of the Morita–Baylis–Hillman reaction. A number of the title compounds with various substituents in the chromene fragment and their deamination products have been synthesized, and their inhibitory activity against butyrylcholinesterase has been studied.

The method of obtaining new heterocyclic compounds - chlorides 2-[(Z)-1-(3,5-diaryl-1,3,4-thiadiazol-2(3H)-iliden)methyl]-3,5-diaryl-1,3,4-thiadiazol-3 was developed. The structure and individuality of the obtained compounds are proved by the physico-chemical methods for the identification of organic compounds: 1Н and 13С NMR, IR spectrometry, mass spectrometry. Antibacterial activity was defined against Escherihia coli, Staphylococcus aureus, Bacillus cereus. It was shown that these compounds have a pronounced antibacterial activity against gram-positive bacteria. The most active compound has been identified, which can potentially be used in medicine as an antimicrobial agent.

The method of obtaining new heterocyclic compound - chloride 2-[(1Z)-1-(3,5-diphenyl-1,3,4-thiadiazol-2(3H)-ilidene)methyl]-3,5-diphenyl-1,3,4-thiadiazol-3-Ia was developed. Its structure was proved by physicochemical methods of identification of organic compounds: 1Н- and 13С-NMR-, IR-spectrometry, mass spectrometry. Antifungal activity was defined against С. albicans, T. rubrum, T. mentagrophytes, F. proliferatum, S. brevicaulis . It was shown that this compound has potent antifungal activity and can potentially be used in medicine as antimicrobial with fungicidal action.