BACKGROUND: Toxic hepatitis is characterized by a significant severity of the course and by high mortality. So, search for effective means of correcting this condition seems to be relevant. It has previously been shown that some thiazolo[5,4-b]indole derivatives are capable to prevent experimental toxic liver damage in laboratory animals. In continuation of this direction, the study of the hepatoprotective properties of synthetic derivatives of thiourea 2-aminobenzothiazole and IEM-2320 was undertaken. AIM: To study the potential hepatoprotective properties of 2-aminobenzothiazole and IEM-2320 in acute carbon tetrachloride poisoning. MATERIALS AND METHODS: Experiments were carried out on 30 male white outbred rats (150–270 g). On a model of carbon tetrachloride poisoning (50% solution of CCl4 in vaseline oil, 0.2 ml/100 g of body weight), the potential hepatoprotective properties of 2-aminobenzothiazole (32 mg/kg) and IEM-2320 (20 mg/kg) were investigated. Ademethionine (Heptral, AbbVie, S.r.L, Italy) at a dose of 20 mg/kg was used as a comparison drug. The studied drugs were administered intraperitoneally 4 times: one hour before the introduction of CCl4, and then — for three subsequent days after the poisoning with CCl4. The results were compared with those of 2 control groups. Animals of the 1st control group were not exposed to CCl4, instead of the studied drugs, they were injected with an equivalent volume of saline solution (0.2 ml/100 g of body weight). Animals of the 2nd control group did not receive any treatment after the CCl4 poisoning. Blood was taken on the seventh day of the experiment. The total contents of protein, glucose, and total cholesterol in blood serum were determined, and the activities of alanine aminotransferase and aspartate aminotransferase were evaluated. RESULTS: Under the CCl4 poisoning, the administration of 2-aminobenzothiazole led to a significant decrease in the concentrations of glucose, total protein, total cholesterol and alanine aminotransferase activity. When IEM-2320 was administered under the condition of poisoning, a decrease in the concentrations of total protein, glucose, urea, total cholesterol, and the alanine aminotransferase activity was observed. CONCLUSIONS: A significant decrease in the biochemical parameters of blood serum after administration of 2-aminobenzothiazole and IEM-2320 under the condition of CCl4 poisoning demonstrates thir potential hepatoprotective properties under acute hepatotropic poisonings.

A series of molecular brushes with a polyfluorene (PF) backbone and polymethacrylic acid side chains of varying lengths were prepared by atom transfer radical polymerization. The structure and composition of the synthesized compounds were confirmed by 1H NMR and IR spectroscopy. Effect of the length of the backbone on spectral and conformational parameters of the macromolecules in solutions was analyzed. The grafting density of side chains was about 90%. Spectral methods have been used to determine the dependence of side chain grafting on the luminescent properties of polymer solutions, including quantum yields. It was shown that an optimal length of polymethacrylic acid side chains provides solubility of the polymer brushes. Solutions of PF-graft-polymethacrylic acid complexes with the model substance curcumin were investigated. It was established that the molecular brushes containing curcumin form monomolecular micelles. Molecular brushes with zinc phthalocyanine, potential systems for photodynamic, and photothermal therapy, were studied. image

The reactions of 1,3-dialkylthioureas with haloacetic acids are considered. The preparation of N-substituted S-carboxymethylisothiuronium salts and their corresponding «free bases» by alkylation of N-substituted thioureas with haloacetic acids are discussed separately.

Crystal structure of a series of 1-alkylimidazole-4,5-dicarboxylic acids has been determined. It is shown that an increase in the length of the alkyl group leads to drastic changes in the crystal and molecular structures. 1-Methyl and 1-ethylimidazole-4,5-dicarboxylic acid crystallize in zwitterionic form, but 1-propyl- and 1-butylimidazole-4,5-dicarboxylic acid crystallize as rare equimolar mixture of neutral and zwitterionic tautomeric forms. The observed changes in the crystal and molecular structures are apparently associated with the steric factor, which determines both the packing method and the tautomeric composition of the unit cell.

Publications on the interaction of thiourea and monochloroacetic acid are discussed from a historical perspective. Information on the intermediate acyclic and final cyclic products of the reaction, its kinetics and mechanism is provided

The reaction of 1,3-dipolar cycloaddition of a stable azomethine ylide formed from ninhydrin and L-proline to activated acetylenic phosphonates was studied. It was found that the reactions proceed under mild conditions with high regioselectivity to form cycloadducts with a spiro[indeno-2,3′-pyrrolizine]-1,3-dione backbone.

NMR spectra of 1-propylimidazole-4,5-dicarboxylic acid and its 1-alkyl C 1 -C 4 derivatives in DMSO- d 6 were studied. It was shown that these compounds are present in the zwitterion form in this solvent. The ionization constants of 1-propylimidazole-4,5-dicarboxylic acid in water were determined and their assignment was carried out, which is compatible with the assumption that this compound has a zwitterionic form in this solvent as well. Quantum chemical calculations confirmed both this assumption and the correctness of the assignment of deprotonation constants, and also allowed us to choose the preferred zwitter-ionic and monoanionic form of 1-propylimidazole-4,5-dicarboxylic acid from several alternative structures.

A series of poly(o-hydroxy amides) were prepared by polycondensation of 3,3ʹ-methylenebis(6-aminophenol) with isophthaloyl chloride or 2-(4-carboxyphenyl)-1,3-dioxoisoindoline-5-carboxylic acid dichloride, and also by copolycondensation of mixtures of this diamine and 4,4ʹ-diaminodiphenyl ether or 1,3-bis(4-aminophenoxy)benzene with isophthaloyl chloride. The properties of the products obtained were studied. Thermal cyclization of poly(o-hydroxy amides) yielded the corresponding poly(benzoxazoles). A film of the poly(o-hydroxy amide) derived from 3,3ʹ-methylenebis(6-aminophenol) and 2-(4-carboxyphenyl)-1,3-dioxoisoindoline-5-carboxylic acid dichloride with 50% elongation at break remains plastic (the enlongation at break exceeds 6%) even after the heat treatment and closure of benzoxazole rings; the elastic modulus of such film is 1.2 times higher than that of the poly(o-hydroxy amide) film containing 1,3-bis(4-aminophenoxy)benzene and isophthaloyl chloride moieties. Formulations allowing formation of an adhesion-strong highly heat-resistant relief with the micrometer size of elements and high dielectric parameters on semiconductor substrates were prepared by adding a photosensitive component of naphthoquinone diazide type to poly(o-hydroxy amide) reactive solutions in 1 : 5 ratio relative to the dry polymer.

The features of reactions of adenine with phenyl glycidyl ether depending on the solvent nature were studied. In DMF in the presence of K2CO3, an N-9-alkyl derivative, an experimental antiviral drug 9-(2-hydroxy-3-phenoxypropyl)adenine, was formed predominantly. During alkylation in acetic acid, besides N-9-, N-3-, and N-7-alkylation products were also isolated. Alkylation of 6-[alkyl(dialkyl)amino]purines with phenyl glycidyl ether in DMF produced N-exo substituted 9-(2-hydroxy-3-phenoxypropyl)adenine analogues.

This review summarizes and analyzes published medicinal chemistry dataregarding physiologically active 2-arylbenzothiazoles – a promising class ofantiproliferative agents and potential diagnostic agents for Alzheimer’sdisease. The data have been examined in the light of SAR approach to theproperties of 2-arylbenzothiazoles and substances bioactivation mechanisms usinglabeled radiopharmaceuticals. The most promising leaders-in-class for whichclinical trials have been recommended or conducted have been highlighted.Synthetic methods for the preparation of 2-arylbenzothiazoles as precursors ofnew-generation drugs have been analyzed in detail. Various methods for thepreparation of fluorine-containing 2-arylbenzothiazoles, including syntheticpathway to antiproliferative drugs PMX 610, 5-F 203, and Phortress have beendescribed. 2-Arylbenzothiazoles future application in biology and medicine hasbeen discussed.

Three-component condensation of urea with formaldehyde and propane-1,3-diamine in a molar ratio of 1 : 3 : 1 leads to the tricyclic 1,3,5,7,11,13,15,17-octaazatricyclo[15.3.1.17,11]docosane-4,14-dione. Condensation of urea with 1,3,7,9,13,15,19,21-octaazapentacyclo[19.3.1.13,7.19,13.115,19]octacosane (2 : 1) also leads to the formation of tricyclic product. As a result of the condensation of urea with formaldehyde and butane-1,4-diamine in the ratio of 2 : 4 : 1, 5,5′-butane-1,4-diylbis(1,3,5-triazinan-2-one) was obtained.

Condensation of 1,3-dialkylthiourea, formaldehyde, and terminal amino acids (C-2, C-3, or C-4) taken in the 1 : 2 : 1 molar ratio has afforded the terminally substituted (3,5-dialkyl-4-thioxo-1,3,5-triazinan-1-yl)carboxylic acids.

The polycondensation of the mixture of diamines 5,5-methylene bis(2-aminophenol) and 4,4-(hexafluoroisopropylidene)dianiline (molar ratio 0.8:0.2) with isophthaloyl dichloride was used to synthesize poly(amido-o-hydroxy amide) (POA-F) - new heat resistant binder of the composites for microelectronics. The copolymer was fractionated, its hydrodynamic, optical, and conformational properties were researched, and molecular masses (ММ) of the fractions were defined. The polydispersity index was estimated. Based on experimental data, calculation of the size of a segment of Kuhn characterizing degree of an intramolecular orientation order and value of coefficients of the equation of Mark-Kuhn-Hauvink for viscometric and diffusion data were performed. It was demonstrated that introducing 20 mol % of the monomer with -CF3- groups does not lead to any changes in conformational properties of the macromolecules and does not change the degree of intramolecular orientational order (the Kuhn segment length). Optical characteristics of POA-F solutions are virtually similar to the corresponding values for POA prepared with the use of single amine-containing component-5,5-methylene bis(2-aminophenol). The received MM distribution for POA-F (prepolymer) provided the solubility of its films in alkaline solutions. The heat resistance (τ5 and τ10-temperatures corresponding to 5% and of 10% PBO-F mass loss of a polymer) of the powders and the films of PBO, PBO-F were determined. The electrophysical parameters-dielectric permittivity (ε) and dielectric loss tangent (tan δ) of the PBO-F films decreased down to 3.30 and 0.017, in comparison 3.40 and 0.025 for PBO respectively.

A novel 4-((3,5-dimethyl-1H-pyrazol-1-yl)phenylthio)phthalonitrile 3 and corresponding zinc phthalocyanine 5 has been synthesized and characterized. There has been investigated the effect of nature of the linker heteroatom (S or O) on spectroscopic, photophysical and photochemical properties of zinc phthalocyanine 5 and zinc phthalocyanine 6, containing 4-(3,5-dimethyl-1H-pyrazol-1-yl)phenoxy moiety. The zinc phthalocyanines 5 and 6 are highly soluble in common organic solvents. The solvatochromic effects were evaluated by changes in UV–Vis spectra. A correlation between the Q band frequency and the refractive index of 20 organic solvents was examined. The aggregation behavior and photochemical properties (quantum yields singlet oxygen generation and photodegradation) of zinc phthalocyanines were investigated at different concentrations in DMSO, DMF, THF and water-organic solvents mixtures. The water content in the mixture has a crucial effect on the aggregation behavior and the generation of singlet oxygen. In DMSO aggregation of 5 takes place with the addition of any amount of water, whereas for 6 the formation of dimers is observed at a water concentration of more than 10%. However, in THF the formation of aggregates is observed at a water concentration above 30% for 5 and 50% for 6. The synthesized novel phthalocyanines have high quantum yield of singlet oxygen (ΦΔ) values (the range of 0.50–0.70) and can be considered as potential photosensitizers for photodynamic therapy. The highest ΦΔ values were obtained for zinc phthalocyanine 6 containing oxygen linker heteroatom in all solvents.

Получены водорастворимые формы для ряда 1-алкил(арил)имидазол-4,5-дикарбоновых кислот. Проведено исследование противосудорожной активности 1-пропилимидазол-4,5-дикарбоновой кислоты и ее триэтаноламмониевой соли на модели NMDA-индуцированных судорог. Показано, что триэтаноламмониевая соль 1-пропилимидазол-4,5-дикарбоновой кислоты обладает противосудорожным действием, в то время как сама кислота — судорожным. Изменение фармакологического профиля вещества связано с образованием ионных пар или ассоциатов, существующих даже в полярной физиологической среде. Способность к ассоциации подтверждена кондуктометрическим методом. Структура соли 1-пропилимидазол-4,5-дикарбоновой кислоты с триэтаноламином установлена методом РСА.

Conditions were found which allow 2-alkyl-substituted imidazole-4,5-dicarboxylic acids to be synthesized in preparative quantities by the oxidation of 2-alkylbenzimidazoles with hydrogen peroxide. It was shown that optimal results can be obtained at the concentration of 2-alkylimidazole in sulfuric acid of 1 M and the hydrogen peroxide: 2-alkylbenzimidazole molar ratio of 11: 1. Oxidation under these conditions results in higher yields of the target 2-alkylimidazole-4,5-dicarboxylic acids, including those with a branched alkyl group.

Reference to the funding source is missing in the article:This study was performed in the framework of the project (no. 10.735.2014/K) and base parts (no. 10.7608.2017/8.9) of state assignment of the Ministry of Education and Science of the Russian Federation in the sphere of research activity.

Water-soluble forms of a series of 1-alkyl(aryl)imidazole-4,5-dicarboxylic acids were prepared. Anticonvulsant activity of 1-propylimidazole-4,5-dicarboxylic acid and its triethanolammonium salt was studied using the NMDA-induced convulsion model. The triethanolammonium salt of 1-propylimidazole-4,5-dicarboxylic acid was shown to possess anticonvulsant activity whereas the acid itself was a convulsant. The change of pharmacological profile was related to the formation of ion pairs or associates even in polar physiological media. The ability to associate was confirmed using conductivity measurements. An x-ray crystal structure analysis was performed for the triethanolammonium salt of 1-propylimidazole-4,5-dicarboxylic acid.