{"title":"几种3-(5-(4-甲氧基苯基)吡唑-3-基)-6- r -[1,2,4]三唑[3,4-b][1,3,4]噻二唑的合成及性质","authors":"S. Fedotov, A. S. Hotsulia, O. Panasenko","doi":"10.14739/2409-2932.2022.2.259227","DOIUrl":null,"url":null,"abstract":"Pyrazole and 1,2,4-triazole derivatives play an important strategic role in modern medicine and pharmacy. This fact is due to the significant possibilities of chemical modification and significant pharmacological potential among the derivatives of these heterocycles. The introduction of 1,2,4-triazole and pyrazole fragments into the structure of new substances allows to influence the formation of a certain type of activity. The structural combination of these heterocycles in one molecule increases the likelihood of interaction with various biological targets. At the same time, the creation of condensed systems involving 1,2,4-triazole is undoubtedly scientifically attractive and promising.\nThe aim of the research was to study the conditions for obtaining 3-(5-(4-methoxyphenyl)pyrazol-3-yl)-6-R-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles and studying the properties of these compounds.\nMaterials and methods. The first stage of the synthetic part of the work involved the use of diethyl oxalate and 1-(4-methoxyphenyl)ethan-1-one with the participation of sodium hydride in toluene. The obtained ethyl 4-hydroxy-4-(4-methoxyphenyl)-2-oxobut-3-ethanoate in the next step was used in the process of conversion into ethyl 5-(4-methoxyphenyl)pyrazole-3-carboxylate with the participation of hydrazine hydrate. Further modification of the molecule was the stepwise formation of the structure of 4-amino-5-(5-(4-methoxyphenyl)pyrazol-3-yl)-1,2,4-triazole-3-thiol. The next stage of the work involved the interaction with carboxylic acids in the environment of phosphorus oxychloride. To determine the composition and identify the structure of the isolated substances, 1H NMR and infrared spectra were recorded, as well as qualitative and quantitative indicators of the elemental composition of the synthesized structures were obtained. The individual nature of the presence of substances and the degree of their purity were determined using high performance liquid chromatography.\nResults. Synthesis of 3-(5-(4-methoxyphenyl)pyrazol-3-yl)-6-R-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles was performed and optimal conditions were determined the process of obtaining these substances. The structure of the products of chemical transformation was confirmed and the results of the study of physical properties were recorded. The results of docking studies allowed to confirm the prospects of the chosen direction of synthetic transformations, which ultimately allowed to determine the biological potential of the obtained compounds. The model enzyme was 14-α-demethylase lanosterol (code 3LD6), information on which was used from the database of the Protein Structures Database (PDB).\nConclusions. As a result of the molecular docking, data were obtained that form an idea of a certain level of probability of the effect of synthesized compounds on the activity of 14α-demethylase lanosterol, which justified the need for further study of antifungal activity.","PeriodicalId":10800,"journal":{"name":"Current issues in pharmacy and medicine: science and practice","volume":"6 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Synthesis and properties of some 3-(5-(4-methoxyphenyl)pyrazol-3-yl)-6-R-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles\",\"authors\":\"S. Fedotov, A. S. Hotsulia, O. Panasenko\",\"doi\":\"10.14739/2409-2932.2022.2.259227\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Pyrazole and 1,2,4-triazole derivatives play an important strategic role in modern medicine and pharmacy. This fact is due to the significant possibilities of chemical modification and significant pharmacological potential among the derivatives of these heterocycles. The introduction of 1,2,4-triazole and pyrazole fragments into the structure of new substances allows to influence the formation of a certain type of activity. The structural combination of these heterocycles in one molecule increases the likelihood of interaction with various biological targets. At the same time, the creation of condensed systems involving 1,2,4-triazole is undoubtedly scientifically attractive and promising.\\nThe aim of the research was to study the conditions for obtaining 3-(5-(4-methoxyphenyl)pyrazol-3-yl)-6-R-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles and studying the properties of these compounds.\\nMaterials and methods. The first stage of the synthetic part of the work involved the use of diethyl oxalate and 1-(4-methoxyphenyl)ethan-1-one with the participation of sodium hydride in toluene. The obtained ethyl 4-hydroxy-4-(4-methoxyphenyl)-2-oxobut-3-ethanoate in the next step was used in the process of conversion into ethyl 5-(4-methoxyphenyl)pyrazole-3-carboxylate with the participation of hydrazine hydrate. Further modification of the molecule was the stepwise formation of the structure of 4-amino-5-(5-(4-methoxyphenyl)pyrazol-3-yl)-1,2,4-triazole-3-thiol. The next stage of the work involved the interaction with carboxylic acids in the environment of phosphorus oxychloride. To determine the composition and identify the structure of the isolated substances, 1H NMR and infrared spectra were recorded, as well as qualitative and quantitative indicators of the elemental composition of the synthesized structures were obtained. The individual nature of the presence of substances and the degree of their purity were determined using high performance liquid chromatography.\\nResults. Synthesis of 3-(5-(4-methoxyphenyl)pyrazol-3-yl)-6-R-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles was performed and optimal conditions were determined the process of obtaining these substances. The structure of the products of chemical transformation was confirmed and the results of the study of physical properties were recorded. The results of docking studies allowed to confirm the prospects of the chosen direction of synthetic transformations, which ultimately allowed to determine the biological potential of the obtained compounds. The model enzyme was 14-α-demethylase lanosterol (code 3LD6), information on which was used from the database of the Protein Structures Database (PDB).\\nConclusions. As a result of the molecular docking, data were obtained that form an idea of a certain level of probability of the effect of synthesized compounds on the activity of 14α-demethylase lanosterol, which justified the need for further study of antifungal activity.\",\"PeriodicalId\":10800,\"journal\":{\"name\":\"Current issues in pharmacy and medicine: science and practice\",\"volume\":\"6 1\",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2022-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current issues in pharmacy and medicine: science and practice\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.14739/2409-2932.2022.2.259227\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current issues in pharmacy and medicine: science and practice","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.14739/2409-2932.2022.2.259227","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
摘要
吡唑和1,2,4-三唑衍生物在现代医学和药学中具有重要的战略地位。这是由于这些杂环化合物的衍生物具有显著的化学修饰可能性和显著的药理潜力。在新物质的结构中引入1,2,4-三唑和吡唑片段,可以影响某种活性的形成。这些杂环在一个分子中的结构组合增加了与各种生物靶点相互作用的可能性。同时,建立含有1,2,4-三唑的缩合体系无疑在科学上具有吸引力和前景。本研究的目的是研究3-(5-(4-甲氧基苯基)吡唑-3-基)-6- r -[1,2,4]三唑[3,4-b][1,3,4]噻二唑的合成条件,并研究这些化合物的性质。材料和方法。第一阶段的合成部分的工作涉及使用草酸二乙酯和1-(4-甲氧基苯基)乙比1- 1,并在甲苯中加入氢化钠。下一步得到的4-羟基-4-(4-甲氧基苯基)-2-氧丁-3-乙醇酸乙酯在水合肼的参与下转化为5-(4-甲氧基苯基)吡唑-3-羧酸乙酯。分子的进一步修饰是逐步形成4-氨基-5-(5-(4-甲氧基苯基)吡唑-3-基)-1,2,4-三唑-3-硫醇的结构。下一阶段的工作涉及在氯氧磷环境中与羧酸的相互作用。为了确定分离物质的组成和结构,记录了1H NMR和红外光谱,并获得了合成结构元素组成的定性和定量指标。用高效液相色谱法测定了物质存在的个体性质及其纯度。合成了3-(5-(4-甲氧基苯基)吡唑-3-基)-6- r -[1,2,4]三唑[3,4-b][1,3,4]噻二唑,并确定了合成这些物质的最佳工艺条件。确定了化学转化产物的结构,记录了物理性质的研究结果。对接研究的结果可以确定合成转化方向的选择前景,从而最终确定所获得化合物的生物潜力。模型酶为14-α-去甲基化羊毛甾醇(代码3LD6),其信息来自Protein Structures database (PDB)数据库。通过分子对接得到的数据表明,合成的化合物对14α-去甲基化酶羊毛甾醇活性的影响有一定的概率,这证明了进一步研究抗真菌活性的必要性。
Synthesis and properties of some 3-(5-(4-methoxyphenyl)pyrazol-3-yl)-6-R-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles
Pyrazole and 1,2,4-triazole derivatives play an important strategic role in modern medicine and pharmacy. This fact is due to the significant possibilities of chemical modification and significant pharmacological potential among the derivatives of these heterocycles. The introduction of 1,2,4-triazole and pyrazole fragments into the structure of new substances allows to influence the formation of a certain type of activity. The structural combination of these heterocycles in one molecule increases the likelihood of interaction with various biological targets. At the same time, the creation of condensed systems involving 1,2,4-triazole is undoubtedly scientifically attractive and promising.
The aim of the research was to study the conditions for obtaining 3-(5-(4-methoxyphenyl)pyrazol-3-yl)-6-R-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles and studying the properties of these compounds.
Materials and methods. The first stage of the synthetic part of the work involved the use of diethyl oxalate and 1-(4-methoxyphenyl)ethan-1-one with the participation of sodium hydride in toluene. The obtained ethyl 4-hydroxy-4-(4-methoxyphenyl)-2-oxobut-3-ethanoate in the next step was used in the process of conversion into ethyl 5-(4-methoxyphenyl)pyrazole-3-carboxylate with the participation of hydrazine hydrate. Further modification of the molecule was the stepwise formation of the structure of 4-amino-5-(5-(4-methoxyphenyl)pyrazol-3-yl)-1,2,4-triazole-3-thiol. The next stage of the work involved the interaction with carboxylic acids in the environment of phosphorus oxychloride. To determine the composition and identify the structure of the isolated substances, 1H NMR and infrared spectra were recorded, as well as qualitative and quantitative indicators of the elemental composition of the synthesized structures were obtained. The individual nature of the presence of substances and the degree of their purity were determined using high performance liquid chromatography.
Results. Synthesis of 3-(5-(4-methoxyphenyl)pyrazol-3-yl)-6-R-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles was performed and optimal conditions were determined the process of obtaining these substances. The structure of the products of chemical transformation was confirmed and the results of the study of physical properties were recorded. The results of docking studies allowed to confirm the prospects of the chosen direction of synthetic transformations, which ultimately allowed to determine the biological potential of the obtained compounds. The model enzyme was 14-α-demethylase lanosterol (code 3LD6), information on which was used from the database of the Protein Structures Database (PDB).
Conclusions. As a result of the molecular docking, data were obtained that form an idea of a certain level of probability of the effect of synthesized compounds on the activity of 14α-demethylase lanosterol, which justified the need for further study of antifungal activity.