1,2,4-triazoles belong to a well-known сlass of heterocyclic compounds that are of both theoretical and practical interest. This class has been known for about 100 years, and in recent decades 1,2,4-triazoles have become one of the most attractive objects of research in the chemistry of heterocyclic compounds due to their unique properties. Recently, a considerable number of innovative synthesis methods have been developed and interesting modification of chemical variations has been proposed, for example, a three-component reaction of aryldiazonium salts with fluorinated diazoreagents and nitriles, or a combination of a fragment of 1,2,4-triazole with coumarins or naphthalene-substituted compounds in one combined molecule, and so on. As a result, scientists have obtained new derivatives of 1,2,4-triazoles with a certain number of structural features that contribute to the production of promising substances with antimicrobial, antifungal, antitubercular, antioxidant, antitumor effects, etc. These derivatives are used not only in the medical and veterinary sphere, but also in the agricultural and industrial sectors. They have found their application as dyes, corrosion inhibitors, photosensitizers, fungicides, plant growth regulators, etc. The aim of our work was to analyze and summarize the known literature data on new synthetic approaches to the production of new derivatives of 1,2,4-triazole and systematize information related to the biological properties of these compounds.
Acute toxicity studies are an integral part of preclinical studies of any new biologically active compound. It should be noted that it is this stage of research that is crucial regarding the possibility of further use of a pharmacologically active substance as a drug. This indicator also helps to determine the initial dose for clinical trials and establish a range of potentially safe doses. The data obtained will help determine the direction of new chemical syntheses, replenish the relevant libraries in silico, as well as reveal many other fundamentally important parameters that characterize the interaction in the compound – living organism system. The aim of this research is to study the acute toxicity of 2-((4-phenyl-5-(thiophene-3-ylmethyl)-1,2,4-triazole-3-yl)thio)sodium acetate. Materials and methods. Previously, a prediction was made using the GUSAR computer program, which helped determine the dose intervals. Acute toxicity was determined by the experimental method of Kerber in vivo using white nonlinear Wistar rats. The rats were weighed, labeled, and divided into five groups of six individuals of each. Results. After the introduction of compound moving activity decreased, drowsiness, pupil miosis, and thirst were observed. In the fifth group, with the maximum dilution, all rats died within two hours after administration of the test compound. During the death, convulsions were observed. In the fourth group five animals died, and in the third – two rats died. In the first two groups, all the rats survived. During follow-up, the animals behaved normally. Based on the results of the research, calculations were made and the LD50 indicator was determined. Conclusions. According to the results, the studied compound belonged to the V class of toxicity (almost non-toxic), and the resulting LD50 value was 1125 mg/kg. This indicator confirmed the prospects for further study of this compound.
Nitrogen-containing heterocyclic compounds are widely represented in modern organic chemistry. A special place among the huge number of substances presented is occupied by derivatives of 1,2,4-triazole due to their uniqueness and prospects. In recent years, these derivatives have remained the object of close attention of both synthetic chemists and researchers engaged in the search for new biologically active substances of a wide spectrum of action, the synthesis of optical materials, dyes, corrosion inhibitors, veterinary drugs, etc. It is known from the literature that the combination of the aromatic heterocycle of thiophene and 1,2,4-triazole is a promising area for research. The result of such combinations is a number of compounds obtained with fairly high yields and a wide range of activities. Thus, further chemical modification of 1,2,4-triazole derivatives by additional administration of a typical thiophene pharmacophore is an urgent task. The aim of the study is to obtain new compounds in a number of S-substituted 5-thiophene-(3-ylmethyl)-4R-1,2,4-triazole-3-thiols and study their physico-chemical properties using complex analysis methods. The study of the physical and chemical properties of the compounds obtained was carried out according to methods that meet the standards of the state pharmacopoeia of Ukraine. The synthesis of new compounds was carried out according to generally accepted methods. The previously obtained 5-thiophene-(3-ylmethyl)-4h-1,2,4-triazole-3-thiol and 5-thiophene-(3-ylmethyl)-4-phenyl-1,2,4-triazole-3-thiol were used as starting compounds. Preparation of thioethanones was performed in an alkaline medium in the presence of methanol. The acids were obtained in an alcohol-alkaline medium with the addition of monochloroacetic acid. To obtain esters, two conventional methods were used. The first method is based on the alkylation in an alkaline-alcohol medium of the starting thiols with isopropyl ester of monochloroacetic acid. The second method is the classical esterification reaction. To confirm the structure and study of the physical and chemical properties, all the resulting compounds were crystallized. As a result, some new compounds that were not previously described were obtained, namely: thioethanones, thioacetamides, thioacetic acids, thioacetates, and a number of other thiopo-derivatives of these initial compounds. The structure and individuality of the obtained molecules were confirmed by elemental analysis (CHNS), IR and 1H NMR spectra. A number of new S-derivatives of 5-thiophene-(3-ylmethyl)-4R-1,2,4-triazole-3-thiols have been obtained. The physical and chemical properties of the obtained compounds are determined and their structure is confirmed using modern analysis methods. Some compounds will be transferred for further research.
Heterocyclic compounds are one of the most important branches of modern organic chemistry and are widely used in medicine, pharmacy, agriculture, and in the production of new materials. One of these compounds is 1,2,4-triazole, which has attracted the attention of scientists around the world for many years. The aim of the work is to synthesize new derivatives of 5-(thiophene-3-ylmethyl)-4R-1,2,4-triazole-3-thiols and study their physical-chemical properties, conducting primary pharmacological screening. Materials and methods. Organic synthesis classical methods were used in the study, as well as a complex of physical-chemical analysis methods (1H NMR spectroscopy, elemental analysis, Elisa and chromato-mass spectral studies) were done. Prediction of pharmacological activity was carried out by using the PASS online computer program. Results. Two initial compounds were obtained: 5-(thiophene-3-ylmethyl)-4phenyl-1,2,4-triazole-3-thiol and 5-(thiophene-3-ylmethyl)-4H-1,2,4-triazole-3-thiol. During their further chemical transformation, a number of new corresponding alkyl derivatives were obtained. The structure of the synthesized compounds was confirmed using modern physical-chemical methods of analysis. Based on the results of pharmacological screening, the high activity of the obtained compounds can be predicted. Conclusions. 5-(thiophene-3-ylmethyl)-4H-1,2,4-triazole-3-thiol, 5-(thiophene-3-ylmethyl)-4-phenyl-1,2,4-triazole-3-thiol and a number of their alkyl derivatives were synthesized. The structure and individuality were proved thanks to modern physical and chemical methods of analysis. Having analyzed the results of primary pharmacological screening of a number of obtained compounds, some of them were selected for further study.
In the latest conditions of development and formation of the pharmaceutical industry, the introduction of new synthetic medicines requires continuous monitoring of the quality and safety of their use. For many years, synthetic drugs have remained an essential tool in the prevention and control of diseases of various etiologies. Among the synthetic class of substances, first of all, those that are low-toxic, safe, and effective deserve attention. In recent decades scientific publications prove the prospects of searching for new biologically active compounds among derivatives of 1,2,4-triazoles with fragments of various heterocyclic systems. Scientists claim that the combination of several structural fragments of heterocycles in one molecule leads to the emergence of new types of biological action, and sometimes to an increase in known pharmacological effects. At the same time, the synthesized compounds belong to the class of low-toxic or practically non-toxic substances. The aim of our work is to analyze foreign and native sources on the biological activity of 1,2,4-triazole derivatives. Conclusions. Among these derivatives, molecules that exhibit broad antifungal and antimicrobial activity, antitubercular, antiviral, actoprotective, antihypoxic, analgesic effects, etc. were found. After analyzing the known data, a number of «structure-action» regularities were established. The obtained results will be useful for further research work of scientists.
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