A targeted search for potential drugs of neurotropic action involves the choice of a basic "pharmacophore", which is advisable to carry out on the basis of the achieved principle among the classes of chemical compounds where active pharmaceutical substances with high targeted activity have already been identified. Therefore, the pyrrolidine core, which is the basic fragment of nootropics of the racetam group, is promising for the rational design of biologically active compounds of nootropic action. Its combination with other heterocyclic fragments, in particular, the 1,2,4-triazole ring, allows for these "hybrid" molecules to expect a permanent change in the magnitude of the pharmacological effects. Creation of a virtual library of compounds, 3D-pharmacophore screening and molecular docking is a promising way to optimize a targeted search for substances with a given pharmacological activity. The aim. To optimize targeted search for new nootropic compounds. Materials and methods. The base generation for the virtual screening was carried out using the Marvin Sketch 20.5 software. For receptor-oriented flexible docking, the Autodock 4.2 software package was used. Results. New derivatives of 1-benzyl-4-pyrrolidin-2-one were selected as the object of the study. Based on the results of the 3D pharmacophore screening and molecular docking to nootropic targets of the virtual base compounds, scoring functions were calculated. A detailed analysis of the geometrical arrangement of "hit compounds" at the active sites of nootropic receptors (PDB ID: 5UOW, 5CXV, 6PV7) made it possible to formulate hypotheses regarding possible ways of interaction of "hybrid" compounds with biotargets. The activity of promising molecules with respect to the studied receptors can be realized by creating complexes between them, the stability of which is ensured mainly due to the energetically favourable geometric arrangement of ligands in the active center of these acceptors, the formation of hydrogen bonds between them, and intermolecular electrostatic and donor-acceptor interactions. Conclusions. Structural modification of the pyrrolidine ring by combining with 1,2,4-triazole scaffold containing substituents of various electronic nature has been proposed. Using 3D-pharmacophore screening, the virtual base of 1-benzyl-4-pyrrolidin-2-one derivatives was analyzed in order to search among them for new molecules of nootropic action. Docking studies have identified a promising group of derivatives of 1-benzyl-4 (4-R-5sulfanylidene-4,5 dihydro-1H-1,2,4-triazol-3-yl) pyrrolidin-2-one, which have affinity for nootropic biotargets and are promising for further synthetic and pharmacological studies

Aim. Using in silico technologies to search for potential SARS-CoV-2 inhibitors among novel tetracyclic ring systems, which are the common core of Crinipellin.Materials and methods. The study object was new compounds previously synthesized via oxidative dearomatization of Crinipellin A. The method of the flexible molecular docking was applied in the study.Results and discussion. Using the molecular docking, the affinity of five compounds for the receptor-ACE2 SARS-CoV-2 (PDB ID: 7DF4), a spike protein SARS-CoV-2 (PDB ID: 1WNC), a PL protein SARS-CoV-2 (PDB ID: 7CJD) and a reverse transcriptase enzyme SARSCoV-2 (PDB ID: 6YYT) was studied. The results of the molecular docking obtained suggest that 8,8-dimethyl-5-(phenylsulfonyl)-3,3a,4,5,8,9-hexahydroindeno[3a,4-b]furan-2(7H)-one may be a potential SARS-CoV-2 inhibitor; it is the basis for its further experimental pharmacological study.Conclusions. The study constitutes one of the stages of searching for SARS-CoV-2 inhibitors. According to the results obtained, a way to search for potential SARS-COV-2 inhibitors based on Crinipellin A derivatives was proposed. Using the most promising compound with hexahydroindeno[3a,4-b]furan core further studies open up another direction for searching for compounds of SARS-COV-2 inhibitors and will save time and laboratory animals while conducting targeted experimental research.

In the current realities the healthcare requires development and introduction of original medicines into production along with manufacture of generic drugs -only this way can raise the pharmaceutical industry of Ukraine to the higher level of quality and to rank it together with the leading European states. In this regard, creation of new effective medicines is a rather topical issue of modern pharmacy. Recently, along with the high pharmacological activity, the simplicity of synthetic methods and availability of the chemical raw material, which provide a relatively law prime cost of finished products, become the most important parameters for the choice of the research objects. With the aim of searching for new biologically active substances we paid attention to the derivatives of 1,3,4-thiadizole, which had already shown themselves as high-efficient bioactive substances exhibiting various types of the pharmacological action [2,3,5,6, 8, 10, 11]. Currently, data on promising applications of derivatives of 1,3,4-thiadiazole for treating cancer appear in scientific literature more often [5,[10][11]. At the moment, the fundamental research of new derivatives are conducted on the basis of this heterocycle as potential antimicrobial agents [3, 6] and аnticonvulsants [2, 8]. Thus, the further search of new bioactive substances among the derivatives of 1,3,4-thiadizole is one of the promising directions.The aim of this work was to extend the range of potential bioactive substances on the basis of 5-R-phenylamino-2-mercapto-1,3,4-thiadiazoles. The synthesis of derivatives of 5-R-phenylamino-2-mercapto-1,3,4-thiadiazoles 1.1-1.2 was carried out by the interaction of carbonic disulphide and R-phenylthiosemicarbazide in the dimethylformamide medium at the temperature of 75°C with satisfactory yields (78-80%) by the known method [8].The structure of the compounds obtained was confirmed by modern physical and chemical methods. Formation of the thiadiazole cycle was proven by the absence of NH-NH signal in the 1 Н NMR-spectra of the compounds synthesized at δ 10.60-10.64 ppm and the presence of a singlet of the mercapto group at approximately 3.40 ppm [1, 9].The target compounds -аnilides of 5-(2,5-dimethoxy) phenylamino-1,3,4-thiadiazole-2-yl-thioacetate acid 3.1-3.8 and аmides of 5-phenylamino-1,3,4-thiadiazole-2-ylthioacetate acid 4.1-4.3 were obtained by S-alkylation with anilidies 2.1-2.8 and alkylamides 2.9-2.11 of chloracetate acid.5-R-phenylamino-2-mercapto-1,3,4-thiadiazoles 1.1-1.2 were obtained in ethanol in the presence of the equimolar quantity of potassium hydroxide according to the Scheme given below.The research results have proven that application of the method allows obtaining the target products with satisfactory yields and sufficient purity (Tab. 1). All compounds obtained after crystallization from ethanol are white crystalline substances with distinct melting points, soluble in most organic solvents (Tab. 1). To study the course of the alkylation reaction when using various alkali reagents the amides of ...

The aim. Selection and development of methods for the tasks of forensic pharmaceutical examination as case materials suspected of falsification or non-medical use of dicyclomine hydrochloride in combination with paracetamol in the form of tablets. Materials and methods. The study presents the developed methods of detection and identification of dicyclomine by TLC, IR spectroscopy and GC-MS, which were performed using reagents that meet the EP, USP and USPU requirements, Class A glassware and qualified devices. Identification by IR spectroscopy was performed in the range from 500 to 4000 cm-1 on the device “Nicolet 380 FT-IR Spectrometer by Thermo Fisher Scientific”. TLC was performed on Sorbfil plates for TLC-PET-H-UV and Sorbfil plates for TLC-AF-UV (CJSC “Sorbpolymer”, Russia). The following systems were used as mobile phases: dioxane-chloroform-acetone-25 % ammonia solution (47.5:45:5:2.5); toluene-acetone-ethanol-25 % ammonia solution (45:45:7.5:2.5); ethyl acetate-methanol-25 % ammonia solution (17:2:1)). The resulting chromatographic zones were detected by irradiation with UV light and further treatment with color reagents (30 % iron (III) chloride solution; Dragendorff's reagent modified by Munier; Marquis reagent; Froehde reagent; Mandelin reagent; FPN reagent). Analysis by gas chromatography with mass detection was performed using a gas chromatograph with a mass spectrometric detector GCMS-QP2020. Data were analyzed using the program: GCMSsolution, LabSolutions Insight (Shimadzu Corporation, Tokyo, Japan). Results. For the first time, the conditions for the extraction of dicyclomine hydrochloride from aqueous solutions were studied and the optimal conditions for their isolation as an object of forensic pharmaceutical examination is defined. The method of detection of dicyclomine hydrochloride and paracetamol in the drug “Trigan-D” by the methods of thin-layer chromatography, gas-liquid chromatography and chromato-mass spectrometry was developed, and the detection limits of the substances under study were determined. Conclusion. The developed methods for dicyclomine hydrochloride in the form of tablets with paracetamol meet the requirements of the current legislation of Ukraine and the Ministry of Justice of Ukraine. The data obtained prove the high sensitivity and reproducibility of the methods and prove the possibility of their introduction into the practice of forensic pharmaceutical examination

A series of 3-substituted guinazolinone derivatives have been synthesized in good to excellent yields and high selectivity by one-pot reaction using anthranilic acid, amine and orthoester in ethanol under mild conditions, respectively. The reaction was efficiently promoted by Bi(OTf)3 and the catalyst could be recovered easily after the reactions and reused without evident loss of reactivity. Docking studies have shown that the tested molecules have an affinity for anticancer targets. The data obtained can be used in planning experimental screening for antitumor activity.