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The spatial structural features of 3-bromo-3-ethoxycarbonyl-2,4-dioxo-1,2,3,4-tetrahydroquinolines have been studied by X-ray analysis. It has been experimentally confirmed that these compounds can be regarded as potential brominating agents.The bromination route of ethyl 1R-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acids using molecular bromine in acetic acid depends on the presence of water in the reaction mixture. Its presence predetermines the formation of 1-R-3-bromo-3-ethoxycarbonyl-2,4-dioxo-1,2,3,4-tetrahydroquinolines. This reaction occurs instantly upon addition of bromine. On the other hand, after thorough dehydration of the reagents and solvent an electrophilic attack occurs only at position 6 of the quinolone ring and in this case completion of the bromination requires several hours [2]. In practice, carrying out the reaction with a strictly stoichiometric ratio of the reacting material and in absolutely anhydrous conditions could not always be achieved. As a consequence there was sometimes observed a partial formation of the 3-bromo-substituted isomers which, in contrast to the colorless 6-bromoquinolines, are bright yellow in color. This process does not, however, cause a significant problem since the high solubility in most organic solvents allows a ready removal of the unwanted admixture from the target 6-bromo derivatives.This formation of the 6-bromoquinolines has been confirmed by us via a counter synthesis using intermediate products with a well known position for the bromine atom in the molecule [3], e.g. from X-ray analysis. At the same time, the steric structural features of their 3-bromo-substituted isomers has remained obscure for a long time.In one of the bromination experiments [2] of ethyl 4-hydroxy-2-oxo-1-propyl-1,2-dihydroquinoline-3-carboxylate (1), prolonged cooling of the filtrate remaining after separation of the basic 6-bromoquinoline 2 at -25ºC caused the growth of several yellow single crystals which were subjected to X-ray analysis.

INTRODUCTION: Along with the efficacy and safety of drugs, the interaction of drugs with each other and with other accompanying substances is important, too. There are no data about the interaction or influence of antacids and other drugs with polyvalent cations on the metronidazole bioavailability. The purpose of this research was the studying of the metronidazole release kinetics from the tablets in an environment that simulates stomach conditions with the addition of metal salts, which are part of the widespread drugs. The research was conducted to assess the impact of possible interactions between the active substance and polyvalent metal cations on their bioavailability and efficacy. MATERIAL AND METHODS: Metronidazole tablets were chosen as research object. 0.1 N HCl solution with addition of metal salts was chosen as medium dissolution. The "PharmaTest-DT70" Device with basket, the "Evolution 60S" Spectrophotometer as well as the "AB 204 S/A METTLER TOLEDO" analytical balances were used in the study. RESULTS:Research of chemical interaction between metronidazole and metal salts, which are part of the widespread drugs, in the experiment "in vitro" was carried out. Metal salts don't influence the metronidazole release from the tablets, as evidenced by dissolution profiles and similarity factors for each of the cases. CONCLUSIONS:The chemical interactions between the chosen medicines were not observed in the "in vitro" experiment. Thus, separate intake of metronidazole with other drugs, containing metal cations, is important for further research in the "in vivo" experiment.

Comparison of chromatographic methods of analysis in a thin layer of the sorbent for identification of famotidine in tabletsToday three national manufacturers produce famotidine tablets, but the SPhU does not contain any monograph for this dosage form.Aim. To verify TLC and study the possibility of using the HPTLC method for identification of famotidine in tablets. Materials and methods. The objects of the study were three batches of famotidine tablets. TLC and HPTLC were used as the methods of the study.Results and discussion. The possibility of using TLC and HPTLC methods for identification of famotidine tablets was confirmed in the study. The main spots of the test solutions corresponded to the size and the Rf value of the main spots of the standard solution. The Rf value for all solutions was 0.5.Conclusions. Thus, TLC as well as HPTLC can be recommended for inclusion to the SPhU; however, HPTLC is more economically advantageous. Порівняння хроматографічних методів аналізу в тонкому шарі сорбенту при проведенні ідентифікації фамотидину у таблеткахМета роботи. На теперішній час три вітчизняних виробники випускають таблетки фамотидину, однак ДФУ не містить монографії на цю форму. Метою дослідження було провести верифікацію ТШХ та вивчити можливість застосування ВЕТШХ для ідентифікації фамотидину в таблетках.Матеріали та методи. Об'єктами дослідження було обрано три серії таблеток фамотидину. Методи дослідження -ТШХ та ВЕТШХ.Результати та їх обговорення. У ході дослідження було підтверджено можливість застосування методик ТШХ та ВЕТШХ для ідентифікації фамотидину у таблетках. Основні плями, отримані при хроматографуванні випробовуваних розчинів, відповідають за розмірами та положенням основній плямі, отриманій при хроматографуванні розчину порівняння. Rf для всіх розчинів становить 0,5.Висновки. Таким чином, як ТШХ, так і ВЕТШХ можуть бути рекомендовані для включення до ДФУ, однак ВЕТШХ є більш економічно вигідною. Ключові слова: фамотидин; ідентифікація; верифікація; тонкошарова хроматографія А. В. Мигаль, М. Маркса, О. С. Головченко, В. А. Георгиянц, Л. Иванаускас Сравнение хроматографических методов анализа в тонком слое сорбента при проведении идентификации фамотидина в таблетках Цель работы. На сегодняшний день три отечественных производителя выпускают таблетки фамотидина, однако несмотря на это, ГФУ не содержит монографии на эту форму. Целью исследования было провести верификацию ТСХ и изучить возможность использования ВЭТСХ для идентификации фамотидина в таблетках. Материалы и методы. Объектами исследования были выбраны три серии таблеток фамотидина, методами исследования были выбраны ТСХ и ВЭТСХ.Результаты и их обсуждение. В ходе исследования была подтверждена возможность использования методик ТСХ и ВЭТСХ для идентификации фамотидина в таблетках. Основные пятна, полученные при хроматографировании испытуемых растворов, соответствуют размерам и положению основного пятна, полученного при хроматографировании раствора сравнения. Rf для всех растворов составил 0,5.Выводы. Таким образом, как ТСХ, так и ВЭТСХ мо...

The aim. Synthesis of 1-benzylsubstituted derivatives of N-[(2,4-dichlorophenyl)methyl]-2-(2,4-dioxo-1h-quinazolin-3-yl)acetamide, and determination of affinity to GABAergic biotargets with the following anticonvulsant activity estimation using PTZ-induced seizures model in mice. Materials and methods. Standard organic synthesis methods were used; the structure of the synthesized compounds was proved by elemental analysis, 1H and 13C NMR spectroscopy, and LC/MS method; composition of the synthesized compounds – by elemental analysis, their individuality – by TLC and LC/MS methods. AutoDockTools-1.5.6, as well as AutoDock Vina software, was used to perform molecular docking. Anticonvulsant activity was studied using pentylenetetrazole-induced seizures in mice. Results. A targeted N-[(2,4-dichlorophenyl)methyl]-2-(1-(R-benzyl)-2,4-dioxo-quinazolin-3-yl)acetamides were obtained by alkylation of N-[(2,4-dichlorophenyl)methyl]-2-(2,4-dioxo-1H-quinazolin-3-yl)acetamide by corresponding 1-chloromethylbenzene in dimethylformamide environment with excess of potassium carbonate at a temperature 70-80 ˚С. Prediction of activity of 1-benzyl derivatives in the pentylenetetrazole-induced seizures in an in vivo experiment was carried out according to the obtained results of docking studies – affinity calculation for GABA receptor and GABA enzyme active sites, as well as analysis of conformational placement in them. In relation to the binding energy, the studied ligands were inferior to the reference drugs: GABA receptor positive allosteric modulators – benzamidine and diazepam, and GABA inhibitor – vigabatrin. The synthesized substances did not show anticonvulsant activity: only 2 compounds have shown a tendency to their activity manifestation according to the criterion of integral protective indicator – reduction of mortality by 17 % compared to control, as well as prolonging the time death of the animals. Comparison with the preliminary obtained results of the activity of the promising anticonvulsant N-[(2,4-dichlorophenyl)methyl] -2-(2,4-dioxo-1H-quinazolin-3-yl) acetamide N-[(2,4-dichlorophenyl)methyl]-2-(2,4-dioxo-1H-quinazolin-3-yl)acetamide made possible to prove the pharmacophore role of the cyclic amide fragment in anticonvulsant activity manifestation. Conclusion. The synthesis of N-[(2,4-dichlorophenyl)methyl]-2-(1-(R-benzyl)-2,4-dioxo-quinazolin-3-yl)acetamides, which have not still described in the literature, was carried out, as well as the structure of the mentioned compounds was proved. Unfortunately, the substances did not show anticonvulsant activity on the model of pentylenetetrazole-induced seizures. However, the obtained results allowed establishing the key role of the NHCO cyclic fragment on anticonvulsant activity. A positive correlation between the results of in vivo studies and in silico calculations was found – the model of pentylenetetrazole-induced seizures and docking into the active sites of PAMs GABAА receptor and enzyme inhibitor GABAАТ, which allows to recommend the given docking methodology as a tool to streamline and optimize the screening on the mentioned model