Functionalized Derivatives of 2-azaspiro[3.3]heptane-1-carboxylic Acid and 7-oxa-2-azaspiro[3.5]nonane-1-carboxylic Acid for Drug Design

2-azaspiro[3.3]heptane-1-carboxylic acid and 7-oxa-2-azaspiro[3.5]nonane-1-carboxylic acid, which had been reported as bioisoster of well-known pipecolic acid, were subjected to chemical transformations, resulting in a number of functionalized derivatives. The obtained molecules contained diversified functional groups, allowing their incorporation in bioactive compounds in versatile modes. Described synthetic approaches afforded multigram-scaled synthesis of the desired compounds with good yields, thus being applicable in drug desig

Reaction of pyrido[2,1-a]isoindole with 1,4-naphtoquinone and study of the product by spectroscopic methods

Key role of the electronic structure of condensed isoindols in the way of the rearrangement was shown. Influence of the dienophile manifests in the requirement of the cyclic form of the dienophile itself. In the reaction of pyrido[2,1-a]isoindole with naphtoquinone rearrangement product of the first type was obtained and its structure was proven by spectral methods. Spectral criteria for the rearranged adducts of the first type for the pyrido[2,1-a]isoindole in the 13C NMR spectra were established. Products of reactions with naphthoquinone, 4-fluoro-, 2,5-difluorophenylmaleimides were isolated and characterized: (2E)-2-[(1,4-dihydroxy-2-naphthyl)(2-pyridin-2-ylphenyl)methylene]-4-hydroxynaphthalen-1(2H)-one, (3E)-1-(4-fluorophenyl)-3-[[1-(4-fluorophenyl)-2,5-dioxopyrrolidin-3-yl](2-pyridin-2-ylphenyl)methylene]pyrrolidine-2,5-dione, (3E)-1-(2,4-difluorophenyl)-3-[[1-(2,4-fluorophenyl)-2,5-dioxopyrrolidin-3-yl](2-pyridin-2-ylphenyl)methylene]pyrrolidine-2,5-dione

Structure and electronic absorption spectra of cyanine dyes – derivatives of tetrazolo- and triazoloisoindole

The electronic structure and absorption spectra of cyanine dyes – tetrazoloisoindole derivatives and triazoloisoindole were calculated. It was shown that these dyes, in terms of their electronic structure, are trimethine cyanine, although formally they are monomethine cyanine. The electron donation of the tetrazoloisoindole and triazoloisoindole residues was determined on the Ilchenko scale, which allows them to quantitatively quantify their Bruker basicity in comparison with the most known heterocyclic end groups of cyanine dyes

Michael addition of heteronucleophilic substances to N – Ar substituted maleimides: green approach

A new method for the preparation of the adducts of aromatic hetero nucleophiles (NH, SH, ОH) to the activated C=C bond of N-aryl-substituted maleimides using Michael reaction was developed. A possibility to obtain mono-adducts was demonstrated for 2-aminopyridine derivatives. It was proven that in the case of amino phenols, which possess three potential nucleophilic centers, only the addition to amino group occurs. Utility of the method for the formation of C–C bond in Michael reaction was also demonstrate

Манипуляция как форма проявления насилия В семье: эмпирический подход к рассмотрению проблемы

The article reflects the results of an empirical understanding of the problem of the manipulative interaction of children in relation to their parents. Based on the results of using the method of theoretical analysis and appealing to the works of both foreign - E. Bern, F. Zimbardo, R. Krauta, D. Price, M. Smith, R. Cialdini, E. Shostroma, and domestic – Afanasieva V.A., Bravoslavska S.V., Dotsenko E.L., Kara-Murza S., Kozachek O.V., Orlova L.V., Chesnokova O.B., Scherban E. and many other scientists, we believe that manipulation as a behavioral manifestation of people towards each other, can be considered not only as a form of influence and pressure, but also as a manifestation of violence. Of particular relevance are issues related to the manipulative interaction of parents in relation to their children and children in relation to their parents (the work of Bern E., Zimbardo F., Kraut R., Price D., Smith M., Shostroma E., Caldini R., etc.); Afanasieva V.A., Bravoslavska S.V., Dotsenko E.L., Kozachek O.V., Kara-Murza S., Orlova L.V., Chesnokova OB, Scherban E., etc.). Based on our analysis of research in the field of interest, we formulate the assumption that children manipulators grow in those families in which parents actively use this form of influence on others. In order to confirm or refute this assumption, we have developed a monitoring program, the implementation of which suggests that our hypothesis is confirmed. It is in those families that use ineffective contacts and forms of interaction with their children (and manipulation, we refer to this category of contacts), children grow up as manipulators, actively applying this form of violent influence on their parents.El artículo refleja los resultados de una comprensión empírica del problema de la interacción manipuladora de los niños en relación con sus padres. Basado en los resultados del uso del método de análisis teórico y atractivo para los trabajos de ambos extranjeros: E. Bern, F. Zimbardo, R. Krauta, D. Price, M. Smith, R. Cialdini, E. Shostroma y domésticos. - Afanasieva VA, Bravoslavska SV, Dotsenko EL, Kara-Murza S., Kozachek OV, Orlova LV, Chesnokova OB, Scherban E. y muchos otros científicos, creemos que la manipulación como una manifestación conductual de las personas entre sí, puede considerarse no solo como una forma de influencia y presión, sino también como una manifestación de violencia. De particular relevancia son los temas relacionados con la interacción manipuladora de los padres en relación con sus hijos y los niños en relación con sus padres (el trabajo de Bern E., Zimbardo F., Kraut R., Price D., Smith M., Shostroma E ., Caldini R., etc.); Afanasieva V.A., Bravoslavska S.V., Dotsenko E.L., Kozachek O.V., Kara-Murza S., Orlova L.V., Chesnokova OB, Scherban E., etc.). Con base en nuestro análisis de investigación en el campo de interés, formulamos la suposición de que los manipuladores de niños crecen en aquellas familias en las que los padres usan activamente esta forma de influencia en los demás. Para confirmar o refutar esta suposición, hemos desarrollado un programa de monitoreo, cuya implementación sugiere que nuestra hipótesis está confirmada. Es en esas familias que usan contactos ineficaces y formas de interacción con sus hijos (y manipulación, nos referimos a esta categoría de contactos), los niños crecen como manipuladores, aplicando activamente esta forma de influencia violenta en sus padres.В статье отражены результаты эмпирического осмысления проблемы манипулятивного взаимодействия детей по отношению к своим родителям. Основываясь на результатах использования метода теоретического анализа и апеллируя к работам как зарубежных-Э. Берн, Ф. Зимбардо, Р. краута, Д. Прайс, М. Смит, Р. Чалдини, Е. Шостром, так и отечественных-Афанасьева В. А., Бравославская С. В., Доценко Е. Л., Кара-Мурза С., Козачек О. В., Орлова Л. В., Чеснокова О. Б., Щербань Е. и многие другие ученые, мы считаем, что манипуляция как поведенческое проявление людей по отношению друг к другу, может рассматриваться не только как форма влияния и давления, но и как проявление насилия. Особую актуальность приобретают вопросы, связанные с манипулятивным взаимодействием родителей по отношению к своим детям и детей по отношению к своим родителям (работы Берна Э., Зимбардо Ф., краута Р., Прайса Д., Смита М., Шострома Е., Кальдини р. и др.); Афанасьева В. А., Бравославская С. В., Доценко Е. Л., Козачек О. В., Кара-Мурза С., Орлова Л. В., Чеснокова О. Б., Щербань Е. и др.). На основе проведенного нами анализа исследований в интересующей нас области сформулировано предположение о том, что дети-манипуляторы растут в тех семьях, в которых родители активно используют эту форму воздействия на окружающих. Для того, чтобы подтвердить или опровергнуть это предположение, мы разработали программу мониторинга, реализация которого предполагает, что наша гипотеза подтверждается. Именно в тех семьях, которые используют неэффективные контакты и формы взаимодействия со своими детьми (а манипуляцию мы относим к этой категории контактов), дети растут как манипуляторы, активно применяя эту форму насильственного воздействия на своих родителей

Synthesis of Compounds of the Pyrimidine Series Based on the Reactions of 3-Arylmethylidenefuran-2(3H)-ones with N,N-Binucleophilic Reagents

The arylmethylidene derivatives of furan-2(3H)-ones are important building blocks for the synthesis of various heterocyclic compounds containing pyrimidine and pyridazine structural fragments, analogues of nitrogen-containing bases of pyrimidine series. In order to continue the development of constructing of molecules containing pyridine and pyridazine fragments, this article is devoted to the synthesis of new biologically active compounds with these moieties. The introduction of a heterocyclic chromenone fragment changes the previously observed 5-R-3-arylmethylidenefuran-2(3H)-ones route of reaction with guanidine carbonate and leads to 3-[(2-amino-4-(2-hydroxyphenyl)pyrimidin-5-yl)methylene]-5-phenylfuran-2(3H)-ones (2a–d). The structure of the reaction products depends on the nature of the aromatic substituent at the C-3 position of the furanone ring. The interaction of 5-aryl-3-arylmethylidenefuran-2(3H)-ones (1e–h) with thiourea in the basic medium leads to the isolation of 5-(2-oxo-2-phenylethyl)-6-aryl-2-thioxotetrahydropyrimidine-4(1H)-ones (3a–d), demonstrating pronounced plant-growth regulatory activity. Optimal conditions for all discussed processes were developed

Straightforward synthesis of tri- and tetra-substituted 3-trifluoromethylfurans by heterocyclization reaction of perfluoroketene dithioacetals

International audienceVarious 2-ethylsulfanyl-3-trifluoromethylfurans were obtained, in moderate to good yields, using a two-step procedure, from perfluoroketene dithioacetals as starting materials. Reaction tolerated a large variety of substituents on the furan nucleus. Mechanism of cyclization was also proposed based on the electronic properties of aryl and heteroaryl substituents

Structure, Z′ = 2 Crystal Packing Features of 3-(2-Chlorobenzylidene)-5-(p-tolyl)furan-2(3H)-one

3-(2-Chlorobenzylidene)-5-(p-tolyl)furan-2(3H)-one (1), C18H13ClO2, crystallizes with Z = 8 and Z′ = 2, and the structure at 100 K has orthorhombic (Pna21) symmetry. Each kind of molecule takes part in π–π stacking interactions to form infinite chains parallel to the c axis. We believe that the existence of two forms can be explained by the probable rotation around a single C–C bond. The quantum chemical modeling reveals that these molecules are almost equivalent energetically, and they can be described as the two most stable conformers (rotamers) with a minor rotational barrier of about 0.67 kcal/mol

Synthesis and biological evaluation of pyridazinone derivatives as potential anti-inflammatory agents

International audienceCyclic nucleotide phosphodiesterase type 4 (PDE4), that controls intracellular level of cyclic nucleotide cAMP, has aroused scientific attention as a suitable target for anti-inflammatory therapy in respiratory diseases. Here we describe the development of two families of pyridazinone derivatives as potential PDE4 inhibitors and their evaluation as anti-inflammatory agents. Among these derivatives, 4,5-dihydropyridazinone representatives possess promising activity, selectivity towards PDE4 isoenzymes and are able to reduce IL-8 production by human primary polymorphonuclear cells