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Аbstract Significance. Nowadays non-steroidal anti-inflammatory drugs have found a wide application in treatment of medical conditions. Despite the clinical effectiveness of non-steroidal anti-inflammatory drugs, their administration is followed by a set of side effects. With aim to reveal the substances with a potency of altering pain threshold in animals, the action of 4-amino-5-methyl-4H-1,2,4-triazol-3-thiones on the nociceptive system in conditions of thermal irritation of rats’ extremities was studied. Aim. Study of the analgesic activity of 4-amino-5-methyl-4H-1,2,4-triazol-3-thiones. Materials and methods. Analgesic activity of the synthesized compounds was evaluated in terms of the set of experiments conducted on white rats of 180-240 g weight. The primary pain threshold after the administration of the substances was assessed using a “hot plate” test, involving a metal plate heated at 55 oC as an irritator. The time of the corresponding response (paw licking, jumping out, squeaking) was measured in seconds. Analgesic activity was assessed by observations of the alterations of pain threshold of the group of studied animals to whom the substances of research were administrated, comparing results with the control group and expressing them in percent. Results. According to the results, it was concluded that the compound of 4-(3,4-dimethoxebenzylidenamino)-5-methyl-4H-1,2,4-triazol-3-thione was the most potent, which reduced the sensitivity to thermal irritation of extremities in the group of animals by 127.78%; that said, its activity is higher than that for the reference drug Analgin, which was also evaluated in a “hot plate” test. It was established that substance (IV) was slightly more active than the reference drug Analgin, demonstrating 121.11% of analgesic activity. Processing of the experimental data revealed some dependencies between the chemical structure and pharmacological activity of the substances of research. Conclusion. The obtained results demonstrate that analgesic activity is existent among the set of 1,2,4-triazole derivatives, which mandates a deeper research of the effectiveness and safety of the most active compounds among the studied compounds.

Derivatives of 1,2,4-triazole are inherent in various types of biological activity. They can be used as pesticide and medicinal drugs (anticonvulsants, analgetics, antitumor and antibacterial). In this regard the search of new methods of synthesis and investigation of biological activity of 2-(4-R-5-(thiophene-2-ylmethyl)-4H-1,2,4-triazole-3-ylthio)acetate acids and their salts is relevant nowadays. With the aim of finding the new biologically active compounds 2-(4-R-5-(thiophene-2-ylmethyl)-4H-1,2,4-triazole-3-ylthio)acetate acids and their salts are synthesized, where R is methyl, ethyl, phenyl. The interaction of 4-R-5-(thiophene-2-ylmethyl)-4H-1,2,4-triazole-3-thions with monochloracetate acid in the medium of i-propyl alcohol in the presence of an equivalent amount of alkali the corresponding 2-(4-R-5-(thiophene-2-ylmethyl)-4H-1,2,4 triazole-3-ylthio)acetate acids are obtained on the basis of which the corresponding salts of morpholine, dimethylamine, monoethanolamine, pteridine, ZnSO4 , CuSO4, NaOH and KOH are obtained and the structure of the received compounds was confirmed on the basis of the data of elemental, IR-, 1H-NMR-spectroscopy. The synthesis of 2-(4-R-5-(thiophene-2-ylmethyl)-4H-1,2,4-triazole-3-ylthio) acetate acids and their salts was conducted. With the help of modern physico-chemical methods: elemental analysis, IR, 1H-NMR-spectroscopy the structure of synthesized compounds, and their individuality by HPLC-MS is proved. In the IR spectrum of the compound 2-(4-phenyl-5-(thiophene-2-ylmethyl)-4H-1,2,4-triazole-3-ylthio)acetate acid Ic available band fluctuations groups characteristic for the nucleus of 1,2,4-triazole: NH– in the range of 3 400–3 100 cm-1,–C=N– – 1 690–1 620 cm-1. Also present band fluctuations groups –C–S– at 691 cm-1. Available band fluctuations characteristic of the group –CH2 within 1496.59 cm-1 and group –COO-H– – 1722.70 cm-1. This suggests the possibility to further study the biological action of the synthesized compounds.

Purposeful synthesis of derivatives of 1,2,4-triazole is one of the most important branches of modern pharmaceutical science Modern pharmaceutical market of domestic medicines requires constant updates of existing range. It makes possible the synthesis of new compounds with a predicted biological activity. The main advantage of derivatives of 1,2,4-triazole is high efficiency and low toxic. That is promising factor for creation of new chemical compounds. Analysis of literary data of past few years has showed that there is not enough information about synthesis, physical, chemical and biological properties of derivatives of 4-amino-5-methyl-4H-1,2,4-triazole-3-thiol in the literature. So synthesis and further research of derivatives of 4-amino-5-methyl-4H-1,2,4-triazole-3-thiol is topical. The research took place at the Department of toxicological and inorganic Chemistry of Zaporizhzhia State Medical University (the head of the department – professor O. I. Panasenko). During the work the research were the physicochemical properties of newly synthesized of compounds in accordance with the methods described in the State Pharmacopoeia of Ukraine. As starting substance was used 4-amino-5-methyl-4H-1,2,4-triazole-3-thiol obtained by cyclization of of potassium 2-atsetilgidrazinkarboditioata in the medium hydrazine hydrate. It is planned to research of the compounds obtained in the antimicrobial, act-protective, antioxidative and hypolipidemic activity. 9 new compounds of ylidene derivatives of 4-amino-5-methyl-4H-1,2,4-triazole-3-thiol were synthesized in a research. The structure of the new synthesized of substances was confirmed by with by means of modern of instrumental methods analysis (1H-PMR-spectroscopy, chromato-mass-spectrometry, elemental analysis). The obtained data is possible to use in purposeful synthesis for the further research of biologically active compounds.

The successful use of drugs, derivatives of 1,2,4-triazole, creates the conditionsfor the production and investigation of properties of new derivatives of this heterocyclic system. The aim of this work was synthesis and study of physical and chemical properties of new derivatives of 1,2,4-triazole-3-thiol containing synthon of pyrrole. The object of the study was a 4-phenyl-5-(pyrrol-2-yl)-1,2,4-triazole-3-ylthio-R-carbothioamides. To achieve this goal it was necessary to solve following tasks: to conduct the selection of the optimum base structure to determine the most efficient way of chemical modification of the precursor of targeted synthesis, to carry out selection of necessary methods of synthesis, to investigate the physico-chemical properties and to set the structure of the obtained compounds. The synthesis of target products of the reaction was carried out using as starting material pyrrole, which with using the form non-catalytic form of reaction of the Fridel-Crafts was transformed into 2,2,2-trichloro-1-(pyrrol-2-yl), ethanol. The resulting material in the result of reaction of hydrazinolysis was converted into the pyrrol-2-carbohydrazide. The obtained intermediate product was used in the reaction of nucleophilic joining of phenylisothiocyanate with subsequent intramolecular alkaline heterocyclization. Synthesized thiol was used in the reaction of alkylation. The structure of the obtained substances are confirmed by using elemental analysis, 1H-NMR-spectroscopy, and their individuality – chromatographic methods of analysis. The resulting substances are an interesting object for further studies, especially biological activity.

Body fatigue has many definitions but in general it can be described as a feeling of heaviness which occurs at the initiation or support physical or mental activities related to work at their normal abilities. Fatigue can be divided into physical and mental fatigue. Fatigue therapy problem is directed to find effective drugs, which affect the mechanisms of fatigue development and are aimed at restoring the cell functions, in particular, increase enzymes activity of the antioxidant defense system. Thus, pharmaceutical and medical practice is more interested in the tools that can help to improve the body's physical abilities and also to postpone fatigue or accelerate the recovery period of the body, but have fewer side effects. In our opinion these future drugs could be the 1,2,4-triazole derivatives which have low toxicity and wide spectrum of pharmacological action. Thus, the objective of our research was to investigate the antifatigue action of 1,2,4-triazole derivatives, as well as establish the patterns between the chemical structure and pharmacological action. The research was carried out on a group of white non-linear rats weighing 163-214. The study of antifatigue activity has been used forced immersion method in water with a load of 10% of the rats weight. Among the alkyl derivatives of 5-(2-methylfuran-3-yl)-4-amino-4H-1,2,4-triazole-3-thiones (2a–g) the most expressive antifatigue action had the 3-octylthio-5-(2-methylfuran-3-yl)-4-amino-1,2,4-triazole (2f). Its application had led to the increasing of the forced swimming duration in comparison with the control group to 15.79%. It should be noted that the 2-methylfuran-3-yl administration to the С5 carbon atom leads to a slight increasing of the antifatigue actions at studied 1,2,4-triazole derivatives. After analyzing the data, we have established some patterns of dependings on the chemical structure of the antifatigue action of the synthesized compounds. For further in-depth research it is recommended to study the compound 1d, which by its antifatigue effect exceeds the referent Riboxinum.

Today, an increase of natural and technogenic situations leads to the disorders of the central nervous system, functional-metabolic processes, vascular diseases, in particular, acute cerebral blood flow disorders. In addition, the changes occurring on the molecular and cellular levels are in the basis of the functional violations of individual systems and the organism as a whole. Hypoxia not only complicates the disease course, but in most cases, determines its outcome. The important role in the fight against hypoxia belongs to antioxidants, which improve the circulating oxygen utilization by the body, reduce its need for the organs and tissues, which is not only expedient but necessary for the treatment of many acute and chronic pathological processes. So, the frequency of the hypoxic states and a wide range of factors causing them determine the relevance of new ways and methods finding to overcome the oxygen deficiency. The aim of this work is the purposeful search of some 5-[((5-(adamantane-1-yl)-4-R-4H-1,2,4-triazole-3-yl)thio)methyl]-N-R1-1,3,4-thiadiazole-2-amines and 5-[((5-(adamantane-1-yl)-4-R-4H-1,2,4-triazole-3-yl)thio)methyl]-4-R1-4H-1,2,4-triazole-3-thiols, the study of their physical and chemical properties and pharmacological screening of the antihypoxic activity of the obtained compounds. Materials and methods. The study of physical and chemical properties was conducted on certified and licensed modern equipment. Antihypoxic activity was studied during the modeling process of hypoxia with hypercapnia. Mexidol was used as a comparison drug in studies at a dose of 100 mg/kg. Results. As the result of the study, it was found that the synthesized compounds and the comparison drug influenced on rats’ life span differently. Compounds, the antihypoxic activity of which exceeded control have been discovered, and others’ were at the level of Mexidol. A number of compounds showed a somewhat less activity in comparison with control, and two compounds, among the investigated ones were weaker then comparison drug action, but they did not reduce the life expectancy of the investigated groups in comparison with control. The effect of the remaining compounds on the lifetime of the investigated group was at the level of control group that received the physiological solution. Conclusions. A series of new compounds of derivatives among 5-[((5-(adamantane-1-yl)-4-R-4H-1,2,4-triazol-3-yl)thio)methyl]-N-R1-1,3,4-thiadiazole-2-amines and 5-(5-(adamantane-1-yl)-4-R-4H-1,2,4-triazole-3-yl)thio)methyl)-4-R1-4H-1,2,4-triazole-3-thiols have been synthesized, the structure of which has been confirmed with the help of modern physical and chemical methods of analysis. The most active compounds among the studied ones were 3a and 2a, their antihypoxic activity exceeds control on 37.86 % and 36.30 % and Mexidol is on 7.35 % and 5.79 % respectively.

It should be noted, that the clinical and therapeutic effect of diuretic drugs is not necessarily associated with an increase diuresis. So, for example, diuretics are also prescribed as a means of dehydration emergency therapy for pulmonary edema, brain, in the integrated therapy of patients with arterial hypertension, with glaucoma, epilepsy, as well as for induction of forced diuresis in poisoning. Therefore, the search for new diuretic agents among heterocyclic systems can solve the problem of treating a complex of diseases of different genesis. The aim of this work was to study the diuretic activity of 4-R-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole derivatives. Materials and methods. The method of E. B. Berchin was used to establish the influence of synthesized compounds on the excretory function of the kidneys. All compounds for this research have been synthesized at the Toxicological and Inorganic Chemistry Department of ZSMU. Results and discussion. Diuretic activity of 4-R-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-thiol derivatives was investigated. Some regularities between “structure – activity” were established: the replacement of the phenyl radical in the 4-phenyl-5-(thiophen-2- ylmethyl)-4H-1,2,4-triazole-3-thiol molecule with ethyl or methyl leads to a slight increase in diuretic effect. The introduction of alkyl radical to 4-R-5-(thiophen-2-ylmethyl)-4H-1,2,4-triasole-3-thiol molecule results in diuretic effect increase. The introduction of 2-chloro-6- fluorobenzyl, 4-hydroxybenzyl and 3,5-dimethoxybenzyl radical to N’-R1 -iden-2-((4-methyl-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazol-3-yl) thio)acetohydrazide molecule also results in diuretic activity increase. Replacement of 3,4-difluorobenzyl radical with 4-fluorobenzyl, 2-bromobenzyl, 2-hydroxybenzyl to N’-R1 -iden-2-((4-phenyl-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazol-3-yl)thio)acetohydrazide molecule results in diuretic activity decrease. Conclusions. The diuretic activity of 4-R-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazoles derivatives was established by the method of Ye. B. Berchin. The derivatives of 4-R-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazoles exhibit both diuretic and antidiuretic effects. Some relationship between “structure – activity” was established. The most active compound was 3-(heptylthio)-4-methyl-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole.

The urgency of the search for new biologically active compounds among the 1,2,4-triasole derivatives is beyond doubt. The promise of this direction has been confirmed by many publications by both domestic and foreign scientists. It is known that various derivatives of 1,2,4-triazole are low-toxic or practically non-toxic compounds, while possessing a wide range of biological effects. As we know, one of the main priorities of the introduction of new substances is a minor toxicity. Therefore, purposeful synthesis of low-toxic compounds and focused study of acute toxicity are the priority tasks of pharmacological research. The aim of the work was to study the acute toxicity of the first synthesized S-derivatives of 4-R-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazoles. Materials and methods. An express method of V. B. Prozorovsky was selected for the study of acute toxicity. The basis of this method is the use of test substances in doses located on a logarithmic scale with an interval of 0.1, and all possible reliable LD50 results and their errors are calculated by pre-program of the probit analysis. Results. As a result of the studies, it was found that the acute toxicity of the synthesized compounds is within the limits of 193–770 mg/kg. According to K. K. Sidorov classification they are low-toxic or practically non-toxic compounds. The most toxic compound among thioles is 4-methyl-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-thiol – 304 ± 65 mg/kg. The acute toxicity of N'-R1-iden-2-((4-methyl-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazol-3-ylthio)acetohydrazides are within the range of 193–770 mg/kg. Conclusions. The acute toxicity of 4-R-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazoles S-derivatives is found to be within the range of 193–770 mg/kg. Some patterns of "structure-acute toxicity" are revealed.

Thanks to the rapid development of science, humanity has achieved remarkable success in various fields. This also applies to the synthesis of biological compounds. Over the centuries, scientists have invented many methods and drugs that are being actively used to date. Derivatives of 1,2,4-triazole can be the foundation for the manufacture of new native drugs that will compete with foreign ones. The aim of work was synthesis and confirmation the structure of 2-((4-(R-amino)-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazol-3-yl)thio)acetate acids salts. Materials and methods. As starting substances we used 2-((4-(R-amino)-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazol-3-yl)thio)acetic acids, which were synthesized by previously described methods. The structure of synthesized compounds was confirmed by the complex use of modern physical-chemical methods of analysis: elemental analysis, 1H-NMR spectroscopy, HPLC-MS. Results. Salts of 2-((4-(R-amino)-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazol-3-yl)thio)acetic acids were synthesized by the interaction of the appropriate acids with organic (morpholin, methanamin, 2-hydroxyethanamin), inorganic basics (aqueous ammonia solution, sodium hydroxide) and salts (zinc sulfate, ferrum (III) chloride, magnesium sulfate, copper (II) sulfate) in alcoholic or aqueous media. Conclusions. A series of novel 2-((4-(R-amino)-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazol-3-yl)thio)acetic acids salts were synthesized. The structure of synthesized compounds is established using modern physical-chemical methods of analysis.

The resistance of microorganisms to antimicrobial and antifungal drugs is still an actual issue in the modern world. Therefore, one of the possible ways to solve this problem is the creation of new drugs. Derivatives of 1,2,4-triazole are interesting in this aspect. In addition a lot of information is published in the scientific literature on the prospects of further research but research data on antimicrobial and antifungal action of 4-R-5-(5-bromthiophen-2-yl)-1,2,4-triazole-3-thiols and 4-R-methylidenamino-5-(thiophen-2-yl)-1,2,4-triazole-3-thiols is missing. The aim of the work. The study of antibacterial and antifungal activity of new 4-R-5-(5-bromthiophen-2-yl)-1,2,4-triazole-3-thiols and 4-R-methylidenamino-5-(thiophen-2-yl)-1,2,4-triazole-3-thiols and establishing the "structure-action" dependence. Materials and methods. For the studied compounds we prepared series of two-fold serial dilutions in Mueller-Hinton broth in a volume of 1 ml using an initial concentration of substance 1 mg/ml. Then in each tube we added 0,1 ml of microbial suspension (106 microbial cells/ml). As a standard test strains we used: Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Candida albicans. All test strains were obtained from the bacteriological laboratory of the State Institution "Zaporizhzhya Regional Laboratory Center for State Sanitary and Epidemiological Service of Ukraine." As a solvent of compounds we used dimethylsulfoxide (99,80%). Additionally a control culture media and solvent were held according to conventional methods. As comparison drugs we used Chlorhexidine-Zdorov'ya® (Ukraine) and Nistatin-Zdorov'ya® (Ukraine). Results. Analyzing the obtained data of antimicrobial and antifungal activity it was revealed that the compounds demonstrated selective antimicrobial action. Thus, 4-amino-5-(5-bromthiophen-2-yl)-1,2,4-triazole-3-thiol showed the highest antimicrobial effect against strains of Staphylococcus aureus exceeding Chlorhexidine and antifungal effect against strains of Candida albicans approaching to comparison drug Nistatin. At the row of 4-R-methylidenamino-5-(thiophene-2-yl)-1,2,4-triazole-3-thiols clear patterns were not found. 4-[(5-nitrofuran-2-yl)methylidenamino]-5-(thiophene-2-yl)-1,2,4-triazol-3-thiol is interesting because of its higher antimicrobial effect than Chlorhexidine against the strains of Escherichia coli and Staphylococcus aureus. For all other compounds minor antimicrobial effect and no antifungal activity were noted. Conclusions. Antimicrobial and antifungal activity of 13 new 1,2,4-triazole-3-thiol derivatives were first time studied. Compounds which showed the highest antimicrobial activity can be used in further biological tests.

In recent years we see significant increase of natural and technogenic situations that lead to disorders of functional and metabolic processes of central nervous system and cardiovascular diseases, including acute cerebrovascular accident. The leading factor in vascular brain pathology is hypoxia. Currently all body states, in which we see any reason decrease of oxygen delivery to tissues is considered as hypoxia. Paying into account the fact that available pharmacotherapeutic agents for the oxygen deficiency treatment tend to have limited efficacy, narrow range of active doses and often cause undesirable side effects, the special attention is paid to drugs that have an antihypoxic action and exclude the above mentioned effects. Aim. To study antihypoxic actions for the first time synthesized derivatives of 1,2,4-triazoles and to find the "structure - action" dependence. Materials and methods. Antihypoxic activity of 1,2,4-triazoles derivatives was studied at modeling hypoxia with hypercapnia. Rats were placed in same volume (1330 ml) sealed up jars, then overturned them down and put in a cell with water to prevent the flow of air. As a comparison drug in the study we used mexidol 100 mg / kg. Results. The study has identified three compounds that extend the comparison drug mexidol and prolong the life expectancy of 59.94 %, 47.79% and 53.31% (compounds 1, 2, 5, respectively). While mexidol was 42.54%. After analyzing the data and chemical structure of the synthesized compounds we have established some relative patterns between chemical structure and antihypoxic actions of 1,2,4-triazoles derivatives. Conclusions. As the result of the study, we have discovered the compound that exceeds the referent drug mexidol on 17.4%. In the study of the acute toxicity of 1,2,4-triazoles derivatives it was found that all compounds belong to IV Class of toxicity (LD50 = 331-770 mg / kg). The presence of two halogen atoms in the molecules of benzylidenhydrazides of 4-R-5-(thiophene-2-ylmethyl)-1,2,4-triazol-3-il) thioacetic acid shows expressive antihypoxic action.

Introduction. The process of new drugs creating includes a plurality of stages, which allow their application in medical practice in the future. These studies are a guarantee of the effectiveness and safety of the test compounds. One of the most important stages of preclinical research is the research of acute toxicity. The data of this experiment gives an estimate of toxic effect of new compounds on the organism of experimental animals that allows to judge about expediency of application of these substances in diseases therapy. The aim of toxicological researches of 4-amino-5-(4-(tert-butyl)phenyl)-4H-1,2,4-triazoles-3-thiol’s derivatives was to establish their damaging effect on the organism of experimental rats and identify possible influence of chemical structure on acute toxicity of the compounds. Methods and results. The tabular rapid-method by V. B. Prozorovsky was chosen. It’s based on the test-compounds dosing according to a logarithmic scale. Two animals were used for the study of one dose of the compound. Animals were pre-weighed and labeled, also an assessment of their external condition was carried out. According to the results of the study, it was found that the compounds belong to the IV class of toxicity according to the classification of K. K. Sidorov. Conclusion. Assessment of toxicity of 31 new compounds, namely derivatives of 4-amino-5-(4-(tert-butyl)phenyl)-4H-1,2,4-triazoles-3-thiol was carried out. The experiments allowed to establish LD50 of test compounds. The most toxic and the least toxic compounds were found. The results of research make it possible to determine some "structure-action" dependence.

Studying new biologically active substances nowadays become increasingly important. The current range of the pharmaceutical market requires constant updating of domestic products. The main requirements for new medications are high efficiency and low toxicity. Aim. Modern pharmaceutical science separates 1,2,4-triazole derivatives as a significant class to create new biologically active compounds. Our purpose is to find novel derivatives of 4-amino-5-methyl-4H-1,2,4-triazole-3-thiol, to study their antimicrobial and antifungal activity. Objects of research are derivatives of 4-amino-5-methyl-4H-1,2,4-triazole-3-thiol. Methods and results. The sensitivity of the microorganisms to the new synthesized compounds was determined by serial dilutions method in accordance with the “methodological guidelines” at the Department of Microbiology, Virology and Immunology (Zaporіzhzhia State Medical University). During initial studies with drug concentrations of 1 mg / ml, a series of two-fold serial dilutions of drug in the Mueller-Hinton solution in a volume of 1 ml were prepared, and then a microbial suspension was added to each tube in amount of 0.1 ml (106 microbial cells/ml). Reference test culture of Gram-positive and Gram-negative bacteria was used for primary screening studies of synthesized substances. As a set of standard test strains we took Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Candida albicans ATCC 885–653. All test strains have been obtained from the bacteriological laboratory of the State institution “Zaporizhzhіa Regional Laboratory Center of the State Sanitary and Epidemiological Service of Ukraine”. As a control of the antimicrobial activity of compounds we used 0.05 % chlorhexidine “Fargomed”. Total results of antifungal and antimicrobial activity. The results showed that the leader compound is 4-((4-brombenzyliden)amino)-5-methyl-4H-1,2,4-triazole-3-thiol, which showed antifungal and antimicrobial activity against Candida albicans MIC – 7,8–62.5 ug/ml, MBtsK – 15.6–250 ug/ml. Recovery of this compound, namely transition to 4-((4-bromobenzyl)amino)-5-methyl-4H-1,2,4-triazole-3-thiol, has no antifungal activity, but demonstrates antimicrobial activity against Staphylococcus aureus. Conclusions. Researches have established some “structure–effect” relationship, and also found the compound, the antifungal activity of which is higher than in the reference chlorhexidine preparation.

Scientific publications of recent years clearly demonstrate the prospects of finding new molecules among 1,2,4-triazole derivatives. The whole series of drugs, which are 1,2,4-triazole derivatives (fluconazole, ribavirin, avesstym, tryfuzol and others), are included into the practice of modern medicine, pharmacy and veterinary. Aim. We have studied and analyzed the available scientific sources over the past five years in order to systematize the available literature of recent years about research regarding heterocyclization reactions of 3-thio- and 3-thio-4-amino derivatives of 1,2,4-triazole. During this studying we used methods of observation, systematization and content analysis. Results. It has been found that a comprehensive approach to an objective analysis of scientific literature confirms the possibility of limitless and very attractive scientific research of new molecules that are formed during heterocyclization of 3-thio- and 3-thio-4-amino derivatives of 1,2,4-triazole. Conclusions. Our research shows the promising future for the new original drugs based on 3-thio- and 3-thio-4-amino substituted of 1,2,4-triazole.

Aim. Analysis of the scientific literature over the past decade has shown that large synthetic possibilities towards creating new and effective drug substances have heterocyclic compounds, in particular the derivatives of 1,2,4-triazole. 1,2,4-Triazole is a structural fragment of many synthetic drugs. The special interest cause ylidene hydrazides of 2-(5-R-1,2,4-triazole-3-ylthio)acetic acids as potential biologically active compounds, among which highly effective medicines can be found. With the aim of finding new biologically active compounds the derivatives of 2-((4-R-5-(thiophene-2-ylmethyl)-4H-1,2,4-triazole-3-yl)thio)aceticohydrazides have been synthesized, their physical-chemical properties have been studied with the use of modern methods, namely elemental analysis, IR,1H-NMR spectroscopy, and their individuality by HPLC-MS. Materials and methods. N'-R1-еden-2-((4-R-5-(thiophene-2-ylmethyl)-4H-1,2,4-triazole-3-yl)thio)aceticohydrazides were received by adding aromatic (2-BrC6H4, 2,3-(OCH3)2C6H3, 3,5-(OCH3)2C6H3, 4-N(CH3)2C6H4, 3,4-F2C6H3, 2-NO2C6H4,4-NO2C6H4, 4-OHC6H4, 2-OHC6H4, 4-FC6H4, 2-CI-6-FC6H3) or heterocyclic (2-SC4H3, 5-NO2-2-C4H2O) aldehyde to an equivalent amount of the appropriate 2-((4-R-5-(thiophene-2-ylmethyl)-4H-1,2,4-triazole-3-yl)thio)aceticohydrazide in the acetic acid medium. The study of physical-chemical properties of obtained compounds was carried out according to the methods outlined in SPU. Chromato-mass-spectral studies were performed on hazarding chromatograph Agilent 1260 Infinity HPLC equipped with mass spectrometer Agilent 6120 with ionization in electro-spray (ESI). Conclusion. This suggests the possibility for further study of biological action of the synthesized compounds. As a result of studies the N'-R1-eden-2-((4-R-5-(thiophene-2-ylmethyl)-4H-1,2,4-triazole-3-yl)thio)aceticohydrazides have been synthesized and their physical-chemical properties have been studied.

Aim. The research of antimicrobial and antifungal activity of 7-((3-thio-4-R-4H-1,2,4-triazoles-3-yl)methyl)theophylline S-derivatives has been erformed. Methods and results. Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Pseudomоnas aeruginosa ATCC 27853, Candida albicans ATCC 885-653 have been taken as a set of standard test-strains. It has been proved that the most active alkyl-derivatives are 7-((3-thio-4-R-4H-1,2,4-triazole-3-yl)methyl)theophylline. Among the synthesized salts, which turned to be active against Staphylococcus aureus, the 2-(5-((theophylline-7-yl)methyl)-4-phenyl-4H-1,2,4-triazole-3-ylthio)acetate ammonium has attracted our attention. Conclusion. The perspective class of compounds for further research on this type of biological activity has been defined.

The purpose of the work was to study the antimicrobial activity of 2-((4-R-3-(morfolinomethylene)-4H-1,2,4-triazole-5-yl)thio) acetic acid salts by "hanging drop" and “serial dilution” methods in broth (limiting concentration option) and establish some patterns of "structure – action" depending. Materials and methods. The objects of research were 9 new compounds of 2-((4-R-3-(morfolinomethylene)-4H-1,2,4-triazole-5-yl)thio) acetic acid salts. These compounds are the crystal substances which are odorless, soluble in water and organic solvents. To achieve a more objective picture of the research we applied two methods: "hanging drop" and “serial dilution” in broth (limiting concentration option). To study the effectiveness of substances we used the test cultures of E. coli, Salmonella typhymurium, Staphylococcus epidermidis, P. aeruginosa. Results and discussion. In the study we have found that 2-((4-R-3-(morfolinomethylene)-4H-1,2,4-triazole-5-yl)thio) acetic acid salts can differently inhibit the growth of test cultures. The results show that the data obtained by two methods correlated with each other. Thus, the 2-((4-R-3-(morfolinomethylene)-4H-1,2,4-triazole-5-yl)thio) acetic acid salts are active against most strains of E. Coli. and Salmonella typhymurium. Analyzing the impact of 2-((4-R-3-(morfolinomethylene)-4H-1,2,4-triazole-5-yl)thio) acetic acid salts we have noted that the replacement of the phenyl radical (PKR-135, 139) on the free amino group at N4 nitrogen of 1,2,4- triazole cycle (PKR-173, 177) leads to the disappearance of antimicrobial activity against the studied strains. It was established that the transition from morfolin cation (PKR-133) to the piperydyn cation (PKR-134) in the molecules of 2-((4-phenyl-3-(morfolinometylen)-4H-1,2,4-triazole-5-yl) thio) acetic acid is accompanied by a significant increase in antimicrobial effect. It was interesting that among all the cations in the molecules of 2-((4-amino-3-(morfolinometylen)-4H-1,2,4-triazole-5-yl) thio) acetic acid salt (PKR-173, 174, 177, 234) only the presence of sodium cation (PKR-174) leads to a pronounced antimicrobial effect against studied strains. Conclusions. The study had found that the most effective in relation to the main groups of pathogenic bacteria are substances PKR-134, 135, 136, 139 and 174. Certain regularities based on "structure-action" have been established, this information can be integrated into future targeted search of substances with antimicrobial properties.

Aim. 1,2,4-triazole derivatives are widely used in medical practice due to its wide range of biological effect and small toxicity. This fact makes this class of organic heterocyclic compounds especially interesting and promising for the study of their physical-chemical and biological properties. Thirteen novel compounds, namely 3-(4- (tert-butyl)phenyl)-5-(R-ylthio)-4H-1,2,4-triazole-4-amines, that were not previously described in the literature, have been synthesized with the aim of search for new potentially biologically active compounds. Methods and results. In order to create new biologically active compounds 13 novel 3-(4-(tert-butyl)phenyl)-5-(R-ylthio)-4H-1,2,4-triazole-4-amines have been synthesized, preparative methods of their synthesis have been proposed, the structure of synthesized compounds has been confirmed by IR-, 1H NMR-spectroscopy, chromatography-mass spectrometry and elemental analysis. In addition, the compounds have been tested for antimicrobial and antioxidative activities. Conclusions. A preparative methods of synthesis of 3-(4-(tert-butyl)phenyl)-5-(R-ylthio)-4H-1,2,4-triazol-4-amines that can be used for chemical modeling of new biologically active compounds are described. The structure of the synthesized compounds was confirmed by complex of modern methods of investigation, namely: IR-, 1H NMR-spectroscopy, chromatography-mass spectrometry and element analysis. This indicates the possibility of using these substances to further biological studies.

Publications of domestic and foreign scientists in the last ten years clearly show that the search for new molecules among 1,2,4-triazole furan derivatives has not only theoretical interest in the study of physical and chemical properties of compounds, but also has a practical significance on the implementation of the most active agents in various spheres of human activity. The most striking example is the registration of new domestic veterinary drug «Tryfuzol 1% solution for injections» (registration certificate AB-05486-01-14 from 01.10.2014). Active substance of the «Tryfuzol» is a water-soluble substance, which is furan derivative of 1,2,4-triazole-3-thione according to the chemical formula. Aim. Further research of reactions which are related to the study of physical and chemical properties of new 1,2,4-triazole-3-thione derivatives with heterocyclic furan system fragments, is an important task in the search for new biologically active compounds needed for the potential drugs creation. Methods and results. For the first time we have synthesized the number of 4-amino-5-(furan-2, 2-metylfuran-3-yl)-1,2,4-triazole-3-thiol alkyl derivatives. As alkylating agents we have used appropriate bromalkans. Conclusions. The structure of the synthesized compounds has been confirmed by complex physical and chemical analysis methods (elemental analysis, NMR spectroscopy, chromatography-mass spectrometry), and their individuality has been confirmed chromatographically.

Aim. To study biological properties of the compounds formed by the combination of the 1,2,4-triazoles, furans and other functional substitutes. Methods and results. It is known that 1,2,4-triazole heterocyclic system is promising for creation of new biologically active molecules. The entire series of drugs, the active ingredient of which is a derivative of the 1,2,4-triazole (fluconazole, ribavirin, avesstim, trifuzol and others) has entered in the practice of modern medicine, pharmacy and veterinary medicine. Special attention to the creation of potential drugs deserves the opportunity of combining fragments of 1,2,4-triazole, the "nucleus" of furan and other substitutes. Literary sources show different types of pharmacological activity of the compounds formed by such "symbiosis". Subsequent chemical transformations of these structures contribute to the establishment of consistent pattern between the structure and biological activity of the corresponding 1,2,4-triazole derivatives, and this in turn has positive effect on the most rapid identification of the most promising classes of compounds. Conclusion. Despite the huge number of publications devoted to the study of the biological properties of the 1,2,4-triazole derivatives with furan fragment, there is no systematization of the results of these research.

The aim of study was to investigate diuretic activity of 1,2,4-triazole derivatives which contain С5 atom 5-bromfuran-2-yl substituent in the 1,2,4-triazole nucleus, and to establish interrelation between chemical structure and diuretic action of 1,2,4-triazole derivatives. Methods and results. For the investigation of the diuretic activity were used 15 compounds, namely 3-(5-bromofuran-2-yl)-4-R-(4H)-1,2,4-triazole-5-thiones, their S-derivatives and 2-(5-bromofuran-2-yl)-5-R'-thiazolo[3,2-b][1,2,4]triazole-6(5H)-ones. During the study Ye. B. Berkhin’s method has been used to establish the influence of the compounds on the renal excretory function. Conclusion. The most active substance among 1,2,4-triazole derivatives was morpholinium 2-((5-bromofuran-2-yl)-4-ethyl-1,2,4-triazole-3-ylthio)acetate.

The amount of antibiotics has increased over the past decade. This also resulted in increase of microorganisms’ resistance to this class of drugs. Therefore, the synthesis of new compounds that have exhibited antimicrobial and antifungal activity and low level of side effects is an important issue of modern pharmacy. The 1,2,4-triazole system is very promising in this aspect. The aim was to study the antimicrobial and antifungal activity of 4-R-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-thiol and 3-(alkylthio)-4-R-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole. Methods and results. In the study "serial dilutions" method has been used. The criteria for the activity of given compound was the minimum inhibitory concentration (MIC) which is the lowest concentration of drug that inhibits the growth of the test culture and the minimum bactericidal concentration (MBC) which is the lowest concentration of drug that causes bactericidal effect. Test compounds are derivatives of 4-R-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-thiol and 3-(alkyl-thio)-4-R-5-(thiophene-2-ylmethyl)-4H-1,2,4-triazole which exhibit antifungal and antimicrobial activity. Conclusion. The most active of the studied 1,2,4-triazole derivatives is 4 (4-methyl-3-(octylthio)-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole), which manifests as antifungal and antimicrobial activity. Some regularity between structure and action has been investigated.

Development of sensitive, acurate, reproducible HPLC-DMD-MS method for determination of the residualamounts of active drug substance "Tryfuzol" in poultryhomogenatesamples and application of this method for testing chiken groups is an important task for the confirmation of thi drug safety. The substance extraction conditions were optimized for methods development. It was established optimum extraction condition. Chromatographic conditions and massspectrometric studies were optimized. As mobilephase, a flowrate of 0.4 ml min-1 isocraticelution 0.1% (v / v) formicacid in water (A) acetonitrile containing 0.1% (v / v) formicacid (B). The composition of the mobile phase of 70% / 30% (v / v). Total running time is 5 minutes. Wave length of the detectoris 276 nm. Control of substances availability was carried by retention time and under UV and massspectra. The technique complies with relevant regulations. The absence of saidsubstance in the study chiken group was proven by using developed techniques.

Aim. Selection, synthesis and biological properties of new compound play major role in creating original medicines. Methods and results. Therefore, to find new bioactive compounds 3-(alkylthio)-4-R-5-(thiophene-2-ylmethyl)-4H-1,2,4-triazoles, where R - methyl, ethyl, phenyl, have been synthesized, by alkylation reaction of 4-R-5-(thiophene-2-ylmethyl)-4H-1,2,4-triazole-3-thiols with 1-bromobutane, or 1-bromopentane, or 1-bromohexane, 1-bromoheptane, 1-bromooctane, 1-bromononane, 1-bromodekane in the n-butanol medium and their physical-chemical properties have been studied using modern physical-chemical methods of analysis, elemental analysis, IR spectroscopy, and their individuality using HPLC-MS. Conclusion. This suggests the possibility of further studying the biological effect of the synthesized compounds.

Aim. To analyze the carbonyl derivatives of 7-((3-thio-4-R-4H-1,2,4-triazole-5-yl)methyl)theophylline their mother substance was synthesized and its interaction with α-haloketones series was carried out. Methods and results. The physical-chemical properties of the obtained compounds have been studied and their structures have been confirmed by elemental analysis, infrared spectrometry, 1H NMR spectrometry, UV spectrophotometry and gas chromatography mass spectrometry. Preliminary computer study of acute toxicity and biological activity has been also carried out. It has been determined that the obtained compounds may exhibit diuretic and analeptic activity and 1,2,4-triazole fragment can theoretically increase it. Conclusion. Preliminary prediction of acute toxicity has showed that the compounds are low-toxic.

Aim. A number of new 3,5-R-4-(3-(5-nitrofuran-2-yl)allylidenami-no)-1-R1-4H-1,2,4-triazole halides have been synthesized, the structure of synthesized compounds has been proved by modern physical-chemical methods. Methods and results. Experimental substantiation of the antimicrobial activity of newly synthesized derivatives of 3,5-R-4-(3-(5-nitrofuran-2-yl)allylidenamino)-1-R1-4H-1,2,4-triazole halides using disco-diffusion method on Mueller Hinton medium has been performed. Conclusion. Analysis of the results of microbiological research allowed to determine the substituent’s influence on the antimicrobial activity of 3,5-R-4-(3-(5-nitrofurans-2-yl)allylidenamino)-1-R1-4H-1,2,4-triazolo halides derivatives. The results indicate the prospects for further study.

Inflammatory process is the leading pathogenic link of many diseases, which constitute about 80% of all pathologies in medical practice of any physician profession. Currently in a complex therapy of acute and chronic diseases a large number of drugs mainly from the group of non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticosteroids areusedas analgesics and anti-inflammatory preparations. NSAIDs is a group of substances with different structure (although, most of them are related to organic acids) with the overall therapeutic and adverse effects. The NSAID prototype is aspirin, so sometimes such drugs are called as similar to aspirin drugs. Most currently usedNSAIDs, inhibit cyclooxygenase-1 (constitutive iso-ferment) and cyclooxygenase-2 (isoferment, induced during the inflammation), disrupting the synthesis of prostaglandins and thromboxanes. The aim of this work was the valuation of anti-inflammatory activity of the 2-(5-((theophylline-7'-yl)methyl)-4-R-4Н-1,2,4-triazole-3-ylthio)-аcetic acidsalts on the model of acute inflammation "formalin-induced edema of the extremities" on rats and establishing the dependenceof pharmacological activityfrom structure. The objects of our research were 14 new compounds, namely salts of 2-(5-((theophylline-7'-yl)-methyl)-4-phenyl-4Н-1,2,4-triazole-3-ylthio)аcetic acid that have been synthesized at the Department ofToxicological and Inorganic Chemistry, of Zaporizhzhia state medical university. These compounds are crystalline substances, unscented, soluble in water or organic solvents. In accordance with the research results it has been found that 2-(5-((theophylline -7'-yl)methyl)-4-R-4Н-1,2,4-triazolo-3-ylthio)acetic acid and its diethylethanol-ammonium salt, by the strength of anti-inflammatory action exceeds the standard of comparison, namely diclofenac,both during 2 hours (at 26,63% and 42,15% respectively, p ˂ 0,01) and during 4 hours (at 1,79% and 6,96% respectively, p ˂ 0,05). Piperidine 2-(5-((theophylline-7'-yl)methyl)-4-phenyl-4Н-1,2,4-triazole-3-ylthio)acetateshould also be noted among the studied substances, as it shows high anti-inflammatory effect, the power of which is close to the action of sodium diclofenac (less active on 6,68%, p ˂ 0,05).