The derivatives of 1,2,4-triazole are of the great scientific interest in the fields of pharmaceutics, agricultural chemistry, and construction The production of Trifuzol-Neo has already been launched, and it is now commercially available. Compounds based on 1,2,4-triazole may also be useful in veterinary practice due to their antiviral activity. Trifuzol-Neo, or piperidinium ([5-(2-furanyl)-4-phenyl-4Н-1,2,4-triazol-3-yl]thio)acetate (Figure 1), has already proved to be an effective immunostimulator for poultry.Since that, the quality control of raw materials and the ready product is required during the production stage. Currently, there is only one method for determination of the assay of Trifuzol-Neo, which involves HPLC-DMD (Center of Medical Research Information and Patent and Licensing Practice of Ukraine. The main disadvantages of HPLC-DMD are the use of relatively high amounts of costly solvents (acetonitrile in this case), considerable baseline instability, and time-consuming system stabilization. Gas-chromatography is able to avoid these constrictions since it involves gas as a mobile phase, which is a more cost-effective and reproducible alternative. The newly developed GC/MS method for Trifuzol-Neo assay determination consists of the following steps: weighing 20.0mg of Trifuzol-Neo powder, dillution in 20mL methanol, injection of 0.5uL of the obtained solution to GC column (at least three times). The same operations are done with a Trifuzol-Neo standard.
Фізико-хімічні властивості S-похідних 5-(3-фторфеніл)-4-аміно-1,2,4-тріазол-3-тіолуЗапорізький державний медичний університет, УкраїнаСьогодні серед багатьох учених користується популярністю спроба поєднання гетероциклу 1,2,4-тріазолу з різними фармакологічно активними фрагментами інших органічних молекул. Раніш нами відзначалось, що введення до структури 1,2,4-тріазолу фторфенільного радикала призводить до формування нових властивостей сполук, а це, своєю чергою, стимулює та надихає учених на пошук нових речовин саме в ряді фторфенілпохідних 1,2,4-тріазол-3-тіолу. Мета роботи -синтезувати нові S-похідні 5-(3-фторфеніл)-4-аміно-1,2,4-тріазол-3-тіолу, дослідити фізико-хімічні властивості вперше отриманих 3-3,4]тіадіазолів здійснені на сертифікованому та ліцензійному обладнанні фізико-хімічних лабораторій Запорізького державного медичного університету згідно з планами дослідження. Подібно до попередніх випадків як вихідну речовину використали гідразид 2-фторбензойної кислоти. Тепер відомо, що синтез 4-амінопохідних 1,2,4-тріазолу здійснюють через проміжну стадію отримання відповідних ксантогенатів. Взявши за основу представлену методику, синтезували 5-(3-фторфеніл)-4-аміно-1,2,4-тріазол-3-тіол. Результати. Будова молекул усіх синтезованих 3-(3-фторфеніл)-6-(арил-, гетерил)-[1,2,4]тріазол[3,4-b][1,3,4]тіадіазолів доведена з використанням сучасних фізико-хімічних методів аналізу (елементний аналіз, 1 H ЯМР-спектроскопія, хромато-мас-спектрометрія), а їхня індивідуальність підтверджена хроматографічно. Сигнали ароматичних протонів 3-(3-фторфеніл)-6-феніл-[1,2,4] тріазоло[3,4-b][1,3,4]-тіадіазолу в 1 H ЯМР-спектрі реєструвались у вигляді дуплетів, триплета та мультиплетів із відповідними хімічними зсувами. Аналізуючи значення констант піків псевдомолекулярних йонів вихідної сполуки та відповідних 3-(3-фторфеніл)-6-(арил-, гетерил)-[1,2,4]тріазол[3,4-b][1,3,4]тіадіазолів, можна з упевненістю стверджувати, що розраховані значення мас відповідають тим, що знайдені у процесі аналізу. Висновки. Використовуючи відому методику синтезу, нами вперше отриманий 5-(3-фторфеніл)-4-аміно-1,2,4-тріазол-3-тіол, який піддали циклізації у присутності відповідних арил-, гетерилкарбонових кислот у середовищі POCl 3 . Отримано при цьому ряд нових 3-(3-фторфеніл)-6-(арил-, гетерил)-[1,2,4]тріазол[3,4-b][1,3,4]тіадіазолів. Проходження реакції циклізації та підтвердження будови 3-(3-фторфеніл)-6-(арил-, гетерил)-[1,2,4]тріазол[3,4-b][1,3,4]тіадіазолів, що одержали, доведено використанням сучасних комплексних методів аналізу (елементний аналіз, 1 H ЯМР-спектроскопія, хромато-мас-спектрометрія). Ключові слова: S-похідні 1,2,4-тріазолу, синтез, фізико-хімічні властивості. Актуальні питання фармацевтичної і медичної науки та практики.
Експериментальна та клінічна фармакологія Experimental and clinic pharmacology
Today, the process of body fatigue has many definitions, but in general it is characterized as a feeling of heaviness arising from the initiation or support of voluntary physical or mental activity associated with working at the level of one’s normal abilities. Fatigue of the body, as a physiological norm, can be divided into physical fatigue and mental fatigue. The solution to the problem of therapy for the process of fatigue should be expressed in the creation of new effective compounds that can affect the mechanisms of fatigue development and can be oriented towards restoration of cell function, as well as increase the activity of enzymes of the antioxidant defense system of the body in a certain way. The aim of our work was to investigate the actoprotective activity of new derivatives of 5-(thiophen-3-ylmethyl)-4-R1-1,2,4-triazole-3-thiol and to establish certain patterns between the chemical structure and pharmacological activity of the studied compounds. The studies used new derivatives of 5-(thiophen-3-ylmethyl)-4-R1-1,2,4-triazole-3-thiol, which were first synthesized in the laboratory of organic synthesis of the Department of Natural Sciences for foreign students and toxicological chemistry of Zaporizhzhia State Medical University. o determine the dosage conditions of the studied compounds, a preliminary study was made of the general toxic effect and acute toxicity of the studied compounds, which was carried out according to the well-known express method of V. B. Prozorovsky, and the degree of toxicity was evaluated by K. K. Sidorov. The experiments were performed on a group of white nonlinear rats weighing 230–245 g. In the study of actoprotective activity was used the method of forced immersion in water with a load of 10% of the weight of the rat. The data obtained were processed statistically using the standard Microsoft Office 2007 software package and “STATISTICA @ for Windows 6.0”. The reliability of intergroup differences according to the experimental data was established using Student’s t-test. The level of statistical significance of differences in research results is p < 0.01. Analyzing the results of the experiment, it was found that some compounds that were studied in a number of new derivatives of 5-(thiophen-3-ylmethyl)-4-R1-1,2,4-triazole-3-thiol have a pronounced actoprotective effect. The actoprotective activity of the new derivatives of 5-(thiophen-3-ylmethyl)-4-R1-1,2,4-triazol-3-thiol was studied. A number of compounds have been identified that are superior in activity to the comparison drug riboxin. In some cases, patterns of the influence of various substituents on the indices of the actoprotective action of the synthesized compounds were established.
There are engaged scientists practically from all over the world to the 1,2,4-triazole system research but the greatest attention deserve the achievements of domestic scientists who managed from the very beginning to register new original medicines in Ukraine. There is no doubt that the original attempt of combining various typical fragments with the nucleus of 1,2,4-triazole is gaining popularity among researchers. The purpose of our work was to synthesized and investigate a row of new 5-(3-fluorophenyl)-4-methyl-1,2,4-triazole-3-thiols by a Sulfur atom, to study the physical-chemical properties of previously unsubscribed compounds. The chemical names of the compounds are given in accordance with the IUPAC nomenclature (1979) and the IUPAC recommendations (1993). Investigations of the physical-chemical properties of the obtained compounds were carried out according to the methods which are given in the State Pharmacopoeia of Ukraine. The melting point was determined on an automatic device for determining the melting point OptiMelt Stanford Research Systems MPA100 (USA). The elemental structure of the new compounds was established on the element analyzer Elementar Vario L cube (CHNS) (standard - sulfanilamide). The data of elemental analysis correspond to the calculated. The 1Н NMR-spectra of the compounds were recorded using a «Mercury 400» spectrometer, the solvent DMSO-d6, the internal standard – tetramethylsilane (TMS) and decrypted using the SpinWorks computer program. Chromate-mass spectra were recorded on an Agilent 6890N/5973N/FID spectrometer produced by Agilent Technologies with a Dean microflow switch. By the experiment results there were obtained eleven previously unidentified individual compounds light yellow and white color which are soluble in organic solvents and insoluble in water. The crystallization process was carried out in isopropanol. Using a complex approach with the use of modern physical-chemical methods of analysis we confirmed the structure of 5-(3-fluorophenyl)-4-methyl-1,2,4-triazole-3-thiol, 3-alkylthio-5-(3-fluorophenyl)-4-methyl-1,2,4-triazole, 1,4-bis((5-(3-fluorophenyl)-4-methyl-1,2,4-triazole-3-yl)thio)propane and 1,4-bis((5-(3-fluorophenyl)-4-methyl-1,2,4-triazole-3-yl)thio)butane. The individuality of the synthesized compounds was confirmed chromatographically, the constants peaks of the pseudo molecular ions of the synthesized compounds coincide with the calculated values of the molecular masses. We first synthesized 5-(3-fluorophenyl)-4-methyl-1,2,4-triazol-3-thiol which was further used as a starting material in the synthesis of new 3-alkylthio-5-(3-fluorophenyl)-4-methyl-1,2,4-triazole, 1,4-bis((5-(3-fluorophenyl)-4-methyl-1,2,4-triazol-3-yl)thio)propane and 1,4-bis((5-(3-fluorophenyl)-4-methyl-1,2,4-triazol-3-yl)thio)butane. Complex physical-chemical methods of analysis confirmed the structure of synthesized compounds.
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