Синтез та діуретична дія 8-амінозаміщених 7-(2-гідрокси-3-п-метоксифеноксипропіл-1)-3-метилксантину

It has been found that natural xanthines, as well as their synthetic analogs, possess the diuretic effect. Analysis of the literature proves that there is a great opportunity of applying synthetic derivatives of N-methylated xanthines as potential diuretics.Aim. To develop preparative methods of the synthesis of 8-aminosubstituted of 7-(2-hydroxy-3-p-metoxyphenoxypropyl-1)-3-methylxanthine and study their physical, chemical and biological properties. Results. The synthesis of a series of 8-aminosubstituted of 7-(2-hydroxy-3-p-metoxyphenoxypropyl-1)-3-methylxanthine was carried out. According to the results of the biological testing the compounds synthesized belong to the toxicity of class IV. 7-(2-Hydroxy-3-p-methoxyphenoxypropyl-1)-8-(furyl-2-methylamino)-3-methylxanthine xanthine shows the highest diuretic activity, and hence, requires a more in-depth study since it is twice more active than hydrochlorothiazide. It should be emphasized that all compounds synthesized exhibit a marked diuretic effect. Experimental part. 8-Bromo-7-(2-hydroxy-3-p-methoxyphenoxypropyl-1)-3-methylxanthine was obtained by heating 8-bromo-3-methylxanthine with p-methoxyphenoxymethyloxirane in butanol-1 and in the presence of N,N-dimethylbenzylamine. 8-Aminosubstitutied of 7-(2-hydroxy-3-p-metoxyphenoxypropyl-1)-3-methylxanthine was obtained by boiling of bromoalcohol with the primary and secondary amines. The structure of the compounds synthesized was unambiguously confirmed by NMR-spectroscopy. The acute toxicity of the compounds obtained was studied by Kerber method. The study of the diuretic activity of the compounds was carried out using Ye. Berkhin method. Hydrochlorothiazide was used as a reference substance. Conclusions. Simple methods for the synthesis of 8-amino-7- (2-hydroxy-3-p-methoxyphenoxypropyl-1)-3-methylxanthines have been developed. The structure of the compounds synthesized has been confirmed by the method of NMR 1H-spectroscopy. The acute toxicity and the diuretic activity of the compounds obtained have been studied.Известно, что как природные ксантины, так и их синтетические аналоги обладают диуретическим действием. Анализ данных литературы свидетельствует о значительной перспективе использования синтетических производных N-метилированных ксантинов в качестве потенциальных диуретических средств. Цель данной работы – разработка препаративных методов синтеза 8-аминозамещенных 7-(2-гидрокси-3-п-метоксифеноксипропил-1)-3-метилксантина и изучение их физико-химических и биологических свойств. Результаты и их обсуждение. Синтезирован ряд 8-аминозамещенных 7-(2-гидрокси-3-п-метоксифеноксипропил-1)-3-метилксантина. По результатам биологических испытаний синтезированные соединения относятся к IV классу токсичности. 7-(2-Гидрокси-3-п-метоксифеноксипропил-1)-8-(фурил-2-метиламино)-3-метилксантин имеет наибольшую диуретическую активность, а следовательно необходимо доскональное изучение, поскольку он более чем в 2 раза активнее  гидрохлортиазида. Необходимо подчеркнуть, что все синтезированные соединения оказывают выраженное диуретическое действие. Экспериментальная часть. 8-Бром-7-(2-гидрокси-3-п-метоксифенокси­пропил-1)-3-метилксантин получен нагреванием 8-бром-3-метилксантина с п-метоксифеноксиметилоксираном в бутаноле-1 в присутствии N,N-диметилбензиламина. 8-Аминозамещенные 7-(2-гидрокси-3-п-метокси­феноксипропил-1)-3-метилксантина синтезированы путем кипячения бромоспирта с первичными и вторичными аминами. Структура синтезированных соединений однозначно доказана методом ПМР-спектроскопии. Острая токсичность синтезированных соединений изучалась по методу Кербера. Изучение диуретической активности полученных соединений проводили по методу Берхина Е. Б. В качестве эталона сравнения использовали гидрохлортиазид. Выводы. Разработаны простые в выполнении методики синтеза 8-аминозамещенных 7-(2-гидрокси-3-п-метоксифеноксипропил-1)-3-метилксантина. Структура синтезированных соединений доказана методом ПМР-спектроскопии. Изучена острая токсичность и диуретическая активность полученных веществ.Відомо, що як природні ксантини, так і їх синтетичні аналоги виявляють діуретичну дію. Аналіз даних літератури свідчить про значну перспективу використання синтетичних похідних N-метильованих ксантинів в якості потенційних діуретичних засобів. Метою даної роботи є розробка препаративних методів синтезу 8-амінозаміщених 7-(2-гідрокси-3-п-метоксифеноксипропіл-1)-3-метилксантину та вивчення їх фізико-хімічних та біологічних властивостей. Результати та їх обговорення. Був синтезований ряд 8-амінозаміщених 7-(2-гідрокси-3-п-метоксифеноксипропіл-1)-3-метилксантину. За результатами біологічних випробувань синтезовані сполуки відносяться до IV класу токсичності. 7-(2-Гідрокси-3-п-метоксифеноксипропіл-1)-8-(фурил-2-метиламіно)-3-метилксантин виявляє найвищу діуретичну активність, а отже потребує більш досконалого вивчення, оскільки він більш ніж у 2 рази активніший за гідрохлортіазид. Необхідно підкреслити, що всі синтезовані сполуки виявляють виразну діуретичну дію.Експериментальна частина. 8-Бромо-7-(2-гідрокси-3-п-метоксифеноксипропіл-1)-3-метилксантин отримали нагріванням 8-бромо-3-метилксантину з п-метоксифеноксиметилоксираном у бутанолі-1 в присутності N,N-диметилбензиламіну. 8-Амінозаміщені 7-(2-гідрокси-3-п-метоксифеноксипропіл-1)-3-метилксантину синтезовані шляхом кип’ятіння бромоспирту з первинними та вторинними амінами. Структура синтезованих сполук була однозначно доведена методом ПМР-спектроскопії. Гостра токсичність синтезованих сполук була вивчена за методом Кербера. Вивчення діуретичної дії отриманих сполук проводили за методом Берхіна Є. Б. В якості еталону порівняння використовували гідрохлортіазид. Висновки. Були розроблені прості у виконанні методики синтезу 8-амінозаміщених 7-(2-гідрокси-3-п-метоксифеноксипропіл-1)-3-метилксантину. Структура синтезованих сполук була доведена методом ПМР-спектроскопії. Вивчена гостра токсичність та діуретична активність отриманих речовин

The preventive destruction of a hazardous asteroid

One means of countering a hazardous asteroid is discussed: destruction of the object using a nuclear charge. Explosion of such an asteroid shortly before its predicted collision would have catastrophic consequences, with numerous highly radioactive fragments falling onto the Earth. The possibility of exploding the asteroid several years before its impact is also considered. Such an approach is made feasible because the vast majority of hazardous objects pass by the Earth several times before colliding with it. Computations show that, in the 10 years following the explosion, only a negligible number of fragments fall onto the Earth, whose radioactivity has substantially reduced during this time. In most cases, none of these fragments collides with the Earth. Thus, this proposed method for eliminating a threat from space is reasonable in at least two cases: when it is not possible to undergo a soft removal of the object from the collisional path, and to destroy objects that are continually returning to near-Earth space and require multiple removals from hazardous orbits

Poetics of Book “Journey of Russian Imperial Sloop “Diana” from Kronstadt to Kamchatka ...” by V. M. Golovnin: Features of Documentary and Fiction Prose

Observations are presented on the features of the documentary and artistic organization of the book by V. M. Golovnin “Journey of Russian Imperial Sloop “Diana” from Kronstadt to Kamchatka...” (1819). Such issues as the thematic content of “Journey...”, the role of the author’s worldview in creating a single artistic whole, and the features of the aesthetic organization of documentary material are considered. The significance of the study is seen in the need to update the memory of the personality and literary work of V. M. Golovnin, an outstanding figure of Russian culture at the beginning of the 19th century. The presented material will allow supplementing with new facts the picture of the genre and style genesis of documentary and artistic genres in the Russian historical and literary process of the early 19th century. The relevance of the study is determined by the attention of modern literary criticism to the poetics of documentary and artistic genres. The novelty of the research is seen in the appeal to a little-known work of Russian literature of the first third of the 19th century. It is reported that the author showed the maritime way of life with its regulations, traditions, experience of intercultural communication. The work is considered in the main thematic lines: everyday life of a round-the-world sea expedition, seascape, battle studies, ethnographic sketches. It is noted that a value-semantic principle is revealed behind the empirical material, which gives the narrative artistic completeness and deeply brings Golovnin's “Journey ...” with the tradition of Russian classical literature

THE EGALITARIAN PRINCIPLES OF THE OLD BOHEMIAN STATEHOOD AND THE LEGAL SYSTEM

Purpose: The article is devoted to the study of egalitarian principles of medieval Czech statehood and the legal system. Methods: The authors pay special attention to the peculiarities of family self-government of the Czech communities, the institution of hazing in land law and the mechanism of reconciliation as an alternative to the death penalty. Findings: The paper proves that tribal remnants of the customary law of the ancient Czech people in the medieval era contributed to the preservation of egalitarian democratic principles of public administration and justice

Spinning and rotating strings for N=1 SYM theory and brane constructions

We obtain spinning and rotating closed string solutions in AdS_5 \times T^{1,1} background, and show how these solutions can be mapped onto rotating closed strings embedded in configurations of intersecting branes in type IIA string theory. Then, we discuss spinning closed string solutions in the UV limit of the Klebanov-Tseytlin background, and also properties of classical solutions in the related intersecting brane constructions in the UV limit. We comment on extensions of this analysis to the deformed conifold background, and in the corresponding intersecting brane construction, as well as its relation to the deep IR limit of the Klebanov-Strassler solution. We briefly discuss on the relation between type IIA brane constructions and their related M-theory descriptions, and how solitonic solutions are related in both descriptions.Comment: 35 pages. Dedicated to the memory of Ian I. Kogan. References adde

New advances in Raman study of polyvinylchloride structure

In this work we investigated Raman spectra of a number of industrial grades of polyvinylchloride powder and films, prepared from solutions in tetrahydrofuran and acetophenone. The number and spectral characteristics of the Raman lines in the spectral regions of the C-Cl stretching vibrations and in the region of the C-H and CH2 stretching vibrations were evaluated

Online Education after the Pandemic: Student Problems and Opportunities Research Using Big Data Tools

This paper presents a scientifically based approach to analyzing large volumes of data from digital traces of students on social networks, which allows you to effectively identify emerging and most discussed problems among students, as well as highlight pain points that provide opportunities for growth, development of universities and improvement of the characteristics of the educational process, support for students etc. The study is based on a thematic analysis of messages published in university communities on the VKontakte social network using big data tools. The study results showed that Russian university students still face a number of challenges, including weak technical infrastructure at universities, a digital divide in access to online education, and negative attitudes towards distance learning.The scientific problem of the study is the contradiction between the existing volume of unstructured data of students’ digital traces in social networks and the lack of a scientifically-based and proven methodological approach to the analysis and evaluation of this voluminous data, which creates obstacles to fundamental research into the relationship between students’ activity in social networks and their satisfaction quality of the educational process. The practical focus is determined in conducting data analysis using big data tools. The findings and evidence-based implications are useful for developing innovative strategies and tools for assessing and supporting students.The results show that the use of big data tools for tracking trends based on digital traces of students on social networks provides highly accurate analytical data and can become the basis for identifying problematic situations in individual universities and the industry as a whole, for data-driven decision-making and management

Applying Aniline for P-doping of PEDOT:PSS Films to Improve Their Conductivity and Efficiency of Perovskite Solar Cells

Poly(3,4- ethylenedioxythiophene):polystyrene sulfonate (PEDOT: PSS) is responsible for hole extraction efficiency and hole transport in the perovskite solar cell structure. The inclusion of PSS reduces the conductivity of the PEDOT films, which inhibits hole transport and results in a low photo current of the perovskite solar cell. In this work, an aniline solution was used as an additive in the PEDOT: PSS thin film to increase electrical conductivity. Two different methods were used to incorporate the additive: surface and volume treatment. The results show that the surface treatment with aniline solution can significantly increase the conductivity of PEDOT: PSS film. Moreover, the photoconversion efficiency of the perovskite solar cell with such a PEDOT: PSS layer is increased 1.5 times compared to the untreated one