The reaction of Reformatsky reagents, obtained from methyl-1-bromocyclopropane-, 1bromocyclobutane-, and 1-bromocyclopentanecarboxylates and zinc, with diimines, derived from terephthalaldehyde, was studied. As a result, a series of novel bis(spiroazetidin-2-ones) was synthesized. It was found that compounds with а cyclopropane fragment are formed in lower yields than cyclobutane and cyclopentane analogues, and ortho-substituents in the aryl moiety at the nitrogen atoms of the substrate hinder cyclization in this case. The structures of the obtained compounds were confirmed by IR, 1H and 13C NMR spectroscopy, elemental analysis, and X-ray diffraction analysis.

The cyclization and competing reactions for growing radical chains based on N -and C -diallyl monomers of new structural types have been investigated with density functional theory with B3LYP/6-311G(d) computations. The study of these reactions of five diallyl monomers, N , N -diallyl- N ′-acetylhydrazine (DAAH) (I), 1,1-diallyl-3-methyl-2-(4-nitrofurazan-3-yl)guanidine (AMNG) (II), tris(diethylamino)diallylaminophosphonium chloride (DAAP-Cl) (III), 2,2-diallyl-1,1,3,3-tetraethylguanidinium chloride (AGC) (IV), 2-[(diallyl)hydroxymethyl]pyrrolidine (AGMP) (V), was carried out. The probability of homopolymerization is the highest in C -diallyl monomers. In neutral N -diallyl monomers, the reaction of intramolecular hydrogen abstraction proceeds more easily, whereas in the case of guanidinium salt, the availability of a charged guanidinium fragment leads to high efficiency of cyclopolymerization. These results are in good agreement with experimental data on the polymerization of N - and C -diallyl monomers of new structural types.

The Reformatsky reagent, derived from the methyl 1-bromocyclohexanecarboxylate and zinc, reacts with N′-(arylmethylidene)benzohydrazides, to form N-(1-aryl-3-oxo-2-azaspiro[3.5]nonan-2-yl)benzamides as a result of intramolecular cyclization of the initial addition products. Structure of the prepared benzamides was proved by single crystal X-ray diffraction analysis. In the case of p-tolualdehyde benzoylhydrazone, the adduct of the Reformatsky reagent to the double carbon–nitrogen bond of the substrate, which not underwent cyclization, was predominantly isolated. The resulting spiroazetidin-2-ones exhibit antinociceptive activity.

The computer program Prediction of Activity Spectra for Substances (PASS), which allows a prediction of the spectrum of biological activity of chemical compounds based on an analysis of their structure(activity relationships, was used to predict the biological activity of new promising derivatives of 2,5-diaryl-8,8-dimethyl-3,6,7,8-tetrahydro-2H-pyrido[4,3,2-de]cinnolin-3-ones. Screening of the compounds found that 2,5-diaryl-8,8-dimethyl-3,6,7,8-tetrahydro-2H-pyrido[4,3,2-de]cinnolin-3-ones could exhibit antibacterial and antifungal activity. The antimicrobial activity of the synthesized compounds was studied against Gram-positive and Gram-negative bacteria and yeast and mold fungi. The compounds were shown to have an inhibitory effect on some types of Gram-positive bacteria and fungi. 8,8-Dimethyl-2-p-tolyl-5-p-chlorophenyl-3,7,8,9-tetrahydro-2H-pyrido[4,3,2-de]cinnolin-3-one had a minimum inhibitory concentration of 48 μg/mL for Gram-positive bacteria and possessed the most pronounced antimicrobial activity of the tested compounds.

Introduction. Hypoxia is a violation of oxidative processes in tissues that occur when oxygen is insufficiently supplied to them or when its utilization is disrupted during biological oxidation. Chronic hypoxic damage plays an important role in the occurrence and development of various diseases, which necessitates the synthesis of new compounds with antihypoxic activity.Aim. The purpose of this study is to synthesize and investigate the antihypoxic activity of 2-aryl-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydroquinoline-4-carboxylic acids and their reaction products with substituted hydrazines.Materials and methods. 2-Aryl-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydroquinoline-4-carboxylic acids (I–VI) were obtained with high yields as a result of the interaction of 4-aroyl-2,4-dioxobutane acids with 3-amino-5,5-dimethylcyclohex-2-enone. Interaction of 2-aryl-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydroquinoline-4-carboxylic acids with benzyl- and (2-phenylethyl)hydrazines 5-aryl-2-benzyl- and 2-(2-phenylethyl)-8,8-dimethyl-3,7,8,9-tetrahydro-2H-pyrido[4,3,2-de]cinnoline-3-ones (VII–XII) were obtained. As a result, 12 compounds were synthesized. The study of the antihypoxic activity of the obtained compounds was carried out in vivo on a model of normobaric hypoxia with hypercapnia.Results and discussion. The synthesized compounds were tested for the presence of antihypoxic action. The most pronounced antihypoxic activity is characteristic of compounds VI and VIII, which have a methoxy group and a methyl radical in the para-position of the phenyl substituent at C5, respectively. The presence of chlorine in the structure of compound III, fluorine in compound X and the absence of substituents (compounds I and VII) contribute to the prohypoxic effect. According to the results of the study, both quinolincarboxylic acids and pyridocinnolines are potential antihypoxants.Conclusion. A comparative analysis of the antihypoxic activity of the synthesized compounds was carried out, the relationship between their structure and severity of action was established, the most active substances were identified.

Introduction. The state of hypoxia, causing damage and cell death, underlies many pathological processes. In addition, hypoxia induces a state of free radical oxidation, which enhances the damaging effect of hypoxic damage. This necessitates the synthesis of new compounds and the creation on their basis of drugs with antihypoxic activity. Aim. The aim of this study is the synthesis and study of the antihypoxic activity of 2,5-diaryl-8,8-dimethyl-3,6,7,8-tetrahydro-2 Н -pyrido[4,3,2- de ] quinnolin-3-ones. Materials and methods. Compounds of the 2,5-diaryl-8,8-dimethyl-3,6,7,8-tetrahydro-2 H -pyrido[4,3,2- de ]quinnolin-3-ones series were obtained as a result of the interaction of 2-aryl-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydroquinoline-4-carboxylic acids c o -tolyl-, p -tolyl-, p -fluoro-, p -nitro-, 2,4,6-trichlorophenylhydrazines. As a result, 10 substances were synthesized, the structure of which was confirmed by IR and 1 H NMR spectroscopy. The study of the antihypoxic activity of the obtained compounds was carried out using the method of normobaric hypoxia with hypercapnia («hypoxia in a jar»). Results and discussion. The studied compounds have different effects on the lifespan of mice under conditions of acute normobaric hypoxia with hypercapnia. Compounds IIIi and IIId, respectively, increased the lifespan of mice most significantly by 26.36 % and 25.64 %, respectively, compounds IIIa, IIIb, IIIg were less significant, compounds IIIc and IIIf had no effect, and compound IIIj had a prohypoxic effect. Conclusion. Compounds with the most pronounced antihypoxic and antioxidant properties have been identified. Thus, further synthesis and study of 2,5-diaryl-8,8-dimethyl-3,6,7,8-tetrahydro-2 H -pyrido[4,3,2- de ]cinnolin-3-ones is reasonable.

The reaction of 3,3'-(1,4-phenylene)bis(1-phenylprop-2-en-1-ones) with the Reformatsky reagent obtained from methyl 1-bromocyclohexanecarboxylate and zinc involves addition of two molecules of the reagent to the conjugated C=C–C=O systems of the substrate. The intermediate adducts undergo intramolecular cyclization via the nucleophilic attack of the enolate oxygen atoms on the carbonyl carbon atoms. The subsequent hydrolysis of the reaction mixture resulted in the isolation of bis(spiro-3,4-dihydropyran-2-ones). The structure of the products was confirmed by X-ray diffraction.

The reactions of 1-benzoyl-2,4-diphenyl-2,3-dihydro-1 H -1,5-benzodiazepine with methyl 1-bromocycloalkanecarboxylates and zinc, followed by hydrolysis of the reaction mixtures, resulted in the formation of spiro-δ-lactams bearing a 2-( N -benzoylamino)phenyl substituent at the nitrogen atom. The product structures were confirmed by X-ray structural analysis, and a mechanism was proposed for the product formation.

The reaction of methyl a-bromoisobutyrate or 1-bromocycloalkanecarboxylates with zinc and 2,5-diphenyl-1,3,4-oxadiazole leads to 5-phenyl-2,4-dihydro-3H-pyrazol-3-one derivatives, with the cycloalkane series affording products of spiro structure. In the case of cyclobutane reactant, 3-phenyl-2,4,5,6-tetrahydropyrano[2,3-c]pyrazole is also formed.

Гепатопротекторную активность соединения 8,8-диметил-5-п-толил-3,4,7,8-тетрагидро-2H-пиридо[4,3,2-de]циннолин-3-она изучали in vivo на модели острого токсического гепатита, индуцируемого тетрахлорметаном. Установлено, что данное соединение влияет на показатели, определяющие уровень свободно-радикального окисления (СРО): малоновый диальдегид (МДА) и диеновые конъюгаты (ДК), а также активность ключевых антиоксидантных ферментов — супероксиддисмутазы (СОД) и каталазы. Гепатопротекторную активность анализировали по уровню активности ферментов — аланинаминотрансферазы (АлАТ) и аспартатаминотрансферазы (АсАТ), щелочной фосфатазы, а также уровня билирубина. Для определения механизма антиоксидантной активности было изучено влияние данного соединения на уровень экспрессии антиоксидантного гена katG, кодирующего каталазу-гидропероксидазу I, и гена sodA, кодирующего Mn-супероксиддисмутазу. Показано, что 8,8-диметил-5-п-толил-3,4,7,8-тетрагидро-2H-пиридо[4,3,2-de]циннолин-3-он обладает антиоксидантной активностью за счет повышения уровня супероксиддисмутазы и каталазы.

The hepatoprotective activity of 8,8-dimethyl-5-p-tolyl-3,4,7,8-tetrahydro-2H-pyrido[4,3,2-de]cinnolin-3-one was studied in vivo using a model of CCl4-induced acute toxic hepatitis. It was found that this compound affected indices determining the level of free-radical oxidation, i.e., levels of malondialdehyde (MDA) and diene conjugates (DC), and the activities of the key antioxidant enzymes superoxide dismutase (SOD) and catalase. Hepatoprotective activity was analyzed using the activity levels of the enzymes alanine aminotransferase (AlAT), aspartate aminotransferase (AsAT), and alkaline phosphatase and the bilirubin level. The mechanism of the antioxidant activity was determined from the effect of this compound on the expression levels of the gene katG encoding catalase-hydroperoxidase I and the gene sodA encoding Mn-superoxide dismutase. It was found that 8,8-dimethyl-5-p-tolyl-3,4,7,8-tetrahydro-2H-pyrido[4,3,2-de]-cinnolin-3-one exhibited antioxidant activity by increasing the SOD and catalase levels.

Abstract Quinazoline derivatives are well known to have a diverse array of therapeutic activities. Unfortunately, “classic” chemical synthesis does not provide an opportunity for the formation of N-phenyl quaternary 1,3-diazinium compounds. A devised nuclear-chemical method of synthesis based on chemical effects of nuclear transformations enables a new way of the direct nitrogen atom phenylation by the nucleogenic (generated by tritium β-decay) phenyl cations in 1,3-diazines, furnishing, based on our prediction, formation of previously unknown derivatives with N-phenyl quaternary quinazolinium scaffold.

A study of ion-molecular reactions of fluoro-substituted phenyl cations with benzopyridine derivatives demonstrated the following: (a) at present only the nuclear-chemical method enables the reaction of a direct phenylation of the nitrogen atom in benzopyridine derivatives, which makes it possible to obtain previously unknown quaternized structures, and (b) generation of nucleogenic phenyl cations with various substituents leads to a simultaneous introduction of the required substituents into the aromatic ring at the nitrogen heteroatom. Quantum-chemical calculations additionally confirmed the assumption about the pathways of the ion-molecular reactions with nucleogenic phenyl cations.

Гепатопротекторную активность соединения 8,8-диметил-5-п-толил-3,4,7,8-тетрагидро-2H-пиридо[4,3,2-de]циннолин-3-она изучали in vivo на модели острого токсического гепатита, индуцируемого тетрахлорметаном. Установлено, что данное соединение влияет на показатели, определяющие уровень свободно-радикального окисления (СРО): малоновый диальдегид (МДА) и диеновые конъюгаты (ДК), а также активность ключевых антиоксидантных ферментов — супероксиддисмутазы (СОД) и каталазы. Гепатопротекторную активность анализировали по уровню активности ферментов — аланинаминотрансферазы (АлАТ) и аспартатаминотрансферазы (АсАТ), щелочной фосфатазы, а также уровня билирубина. Для определения механизма антиоксидантной активности было изучено влияние данного соединения на уровень экспрессии антиоксидантного гена katG, кодирующего каталазу-гидропероксидазу I, и гена sodA, кодирующего Mn-супероксиддисмутазу. Показано, что 8,8-диметил-5-п-толил-3,4,7,8-тетрагидро-2H-пиридо[4,3,2-de]циннолин-3-он обладает антиоксидантной активностью за счет повышения уровня супероксиддисмутазы и каталазы.

Ethyl 2-amino-5-(2-aryl-2-oxoethylidene)-4-oxo-1H-4,5-dihydrofuran-3-carboxylates and 2-amino- 5-(2-aryl-2-oxoethylidene)-4-oxo-1H-4,5-dihydrofuran-3-carbonitriles reacted with alcohols in the presence of a catalytic amount of concentrated aqueous HCl to give the corresponding 5-alkoxy-2-amino-5-(2-aryl-2- oxoethyl)-4-oxo-1H-4,5-dihydrofuran-3-carboxylic acid derivatives. A probable reaction mechanism was proposed on the basis B3LYP/6-311G(d) quantum chemical calculations.

ИССЛЕДОВАНИЕ ВЗАИМОДЕЙСТВИЯ 2-АРИЛ-7,7-ДИМЕТИЛ-5-ОКСО-5,6,7,8-ТЕТРАГИДРОХИНОЛИН-4-КАРБОНОВЫХ КИСЛОТ С БЕНЗОИЛ-И ИЗОНИКОТИНОИЛ-ГИДРАЗИНАМИ Статья посвящена синтезу 5-арил-8,8-диметил-8,9-дигидро-2Н-пиридо[4,3,2-de]циннолин-3(7Н)онов на основе взаимодействия 2-арил-7,7-диметил-5-оксо-5,6,7,8-тетрагидрохинолин-4карбоновых кислот с бензоил-и изоникотиноилгидразинами.Обсуждается схема реакции.

КАФЕДРЕ ОРГАНИЧЕСКОЙ ХИМИИПЕРМСКОГО ГОСУДАРСТВ ЕННОГО УНИВЕ РСИТЕ

The review describes the history of development of organic chemistry in higher schools of Russia over a period of 170 years, since the emergence of organic chemistry in our country till now.