A series of new Co(II), Ni(II), and Cu(II) metal chelates based on 1-phenyl-3-methyl-4-formyl-5-pyrazolone and 1-aminobenzimidazole derivatives was obtained. The composition and spectral properties were studied by elemental analysis, 1H NMR spectroscopy (for HL), and IR spectroscopy. The parameters of the local atomic environment of the metal ions in these complexes were determined by X-ray absorption spectroscopy. The experimental structural data were confirmed by calculations of the optimized complex structures using density functional theory. The important role of additional donor centers (S, Se) and substituents at the imine nitrogen atom in the aminobenzimidazole fragment of the ligands in the geometry of the coordination site of the complexes was demonstrated.

New coordination compounds of copper(I), copper(II), cobalt(II), and nickel(II) with 2,4-dimethylpyrazolo[1,5-а]benzimidazole (L) were synthesized and studied. The complexes [CuLCl] (I), [CuLBr] (II), [CuL2Cl2] (III), [CuL2(NO3)2]·H2O (IV), [CoL2Cl2]·0.5H2O (V), [CoL2(NO3)2]·0.5H2O (VI), and [NiL2(NO3)2]·0.5H2O (VII) were studied by IR spectroscopy and powder and single crystal X-ray diffraction (CCDC nos. 2321779 ([CuL2Cl2]), 2321780 ([CoL2(NO3)2])). The results indicate that the coordination polyhedron in 2,4-dimethylpyrazolo[1,5-а]benzimidazole complexes is formed by the nitrogen atoms of the monodentate ligand and the coordinated anion. The cytotoxic and cytostatic properties of L and complexes I–III were studied in relation to the HepG2 hepatocellular carcinoma cells.

2,3-Dihydro-1H-imidazo[1,2-a]benzimidazole in acetic acid, and its N-1-Me derivative in CHCl3, are brominated at position 6 with bromine. Less nucleophilic N-9-R derivatives do not enter into the reaction under these conditions, but, like their N-1-R isomers, they are quite effectively brominated by the KBrO3-HBr system, but at position 7, probably due to the transition of the reaction to the mode of bromination of protonated forms of substrates. N-1- and N-9-alkyl-6(7)-Br-2,3-dihydroimidazo[1,2-a]benzimidazoles can also be obtained by N-alkylation of 6(7)-Br-2,3-dihydroimidazo[1,2-a]benzimidazoles under neutral or basic conditions.

The reduction of 7-nitro-N(9)-substituted 2,3-dihydroimidazo[1,2-a]benzimidazoles with SnCl2 in conc. HCl forms a mixture of the previously unknown 7-amino and 7-amino-6-chloro derivatives in a ratio depending on the nature of the substituent at position 9. This result gave grounds to assume that not the final heteroarylamine, but the intermediate heteroarylhydroxylamine formed by a mechanism similar to the acid-induced Bamberger rearrangement of arylhydroxylamines, is subjected to chlorination.

Осуществлен синтез двух комплексов Co(III) на основе 2-{(E)-[2-(гидрокси(алкил)амино)бензимидазол-1-ил]иминометил}фенола (H3L1 и H3L2, алкил — этил или пропил). Методами элементного анализа и ИК спектроскопии установлено, что полученные комплексы имеют составы [Co(H2L1)(HL1)]·2C2H5OH и [Co(H2L2)(HL2)]CH3OH·1/2H2O. Их кристаллическое и молекулярное строение определено методом монокристальной рентгеновской дифракции. Из данных РСА установлено, что они кристаллизуются в три­клинной пространственной группе P–1 в виде сольватов с молекулами спиртов и воды. В моноядерных молекулах обоих комплексов к катиону Co(III) координированы два трисхелатных лиганда в моно- и дианионной формах. Координационное окружение атома кобальта CoN4O2 в обоих соединениях соответствует искаженному октаэдру.

New coordination compounds of cobalt(II), nickel(II), and copper(II) halides with 2-(3,5-dimethylpyrazol-1-yl)benzimidazole (L) of the composition [CoLCl2] (1), CoL2Cl2 · 2H2O · EtOH (2), [NiL(H2O)4]Cl2 · H2O · EtOH (3), NiL2Cl2 · 2H2O · EtOH (4), and [CuL2Br]Br · H2O (5) were synthesized. The compounds were characterized by electronic (diffuse reflectance) spectroscopy, IR spectroscopy, and powder X-ray diffraction. The crystal structures of compounds 1, 3, and 5 were determined by single-crystal X-ray diffraction. The cytotoxic properties of the ligand and compound 5 were evaluated in the Hep-2 cell line.

New coordination compounds of copper(II) halides with 2-(3,5-dimethylpyrazol-1-yl)benzimidazole (L) are synthesized: CuLCl2 (I), [CuL2Cl]Cl⋅H2O⋅C2H5OH (II), and CuLBr2 (III). The compounds are characterized by IR spectroscopy, X-ray diffraction analysis, and static magnetic susceptibility. The crystal structure of compound II is determined by X-ray structure analysis (CIF file CCDC no. 2043452). The cytotoxic properties of ligands L and complexes I and II are studied.

Ethyl 2-formyl-9-methyl-9H-imidazo[1,2-a]benzimidazole-3-carboxylate was synthesized for the first time in a high yield by heating a solution of ethyl 2-(dibromomethyl)-9-methyl-9H-imidazo[1,2-a]benzimidazole-3-carboxylate in ethanol. Acid hydrolysis of the product gave less accessible 9-methylimidazobenzimidazole-2-carbaldehyde. Ethyl 2-formyl-9-methyl-9H-imidazo[1,2-a]benzimidazole-3-carboxylate underwent cyclization to fused oxopyridazine derivative by treatment with hydrazine hydrate, it reacted as a typical aldehyde with acetophenones, hydroxylamine hydrochloride, and malononitrile, and its reaction with acetylacetone and thiourea (Biginelli reaction) afforded the corresponding pyrimidine derivative.

Treatment of 2-[(4-hydroxybutyl)amino]-1H-benzimidazole with ω-bromoacetophenones gave 1-aroylmethyl-substituted derivatives which underwent cyclization to 2-aryl-1-(4-bromobutyl)imidazo[1,2-a]benzimidazole hydrobromides on heating in concentrated hydrobromic acid when Ar = Ph, 4-ClC6H4, 4-BrC6H4, and 4-O2NC6H4. The corresponding bases were readily converted into peri-fused tetrahydro[1,3]diazepino[1,2-a]benzimidazoles via intramolecular alkylation with closure of seven-membered ring. If an electron-donating methoxy group was present in the aryl fragment of the initial ketone, 1-(4-hydroxyphenyl)-2-[2-(pyrrolidin-1-yl)-1H-benzimidazol-1-yl]ethan-1-one was formed in the reaction with HBr.

Изучена антидепрессивная активность 11-[4-трет-бутилбензил]-2,3,4,5-тетрагидро[1,3]диазепино[1,2-a]-бензимидазола гидробромида (ДАБ-19), и его возможных взаимодействий с ГАМК-рецепторами и основными катехоламинами ЦНС, а также моноаминоксидазной активности. По результатам проведенного исследования показано, что ДАБ-19 в дозе 2,34 мг/кг обладает умеренной антидепрессивной активностью на модели «Принудительное плавание по Porsolt», (78,0 ± 7,30) с для ДАБ-19 и (98,32 ± 11,54) с для группы контроля, и «Подвешивание за хвост», (110,1 ± 12,67) с для ДАБ-19 и (168,6 ± 10,2) с для контроля, на мышах (p ≤ 0,05). По результатам тестов «Апоморфиновая стереотипия» и «Стереотипия, обусловленная введением L-ДОФА» не было выявлено дофаминергической и моноаминоксидазной активности ДАБ-19 (p ≤ 0,05). Предположено наличие α2-адреноблокирующего и серотонинактивирующего действия изучаемой субстанции в тестах «5-Гидрокситриптофановый гиперкинез» и «Клофелиновая гипотермия». Антагонизм ДАБ-19 в дозе 2,34 мг/кг с флумазенилом (1 мг/кг) свидетельствует о связи психотропной активности ДАБ-19 с ГАМК-бензодиазепиновым рецепторным комплексом: время, проведенное животными в светлом рукаве для ДАБ-19 составило (78,6 ± 12,13) с, для ДАБ-19 + флумазенил — (6,7 ± 4,59) с (p ≤ 0,05).

Antithrombotic activity of a novel tricyclic derivative of diazepino[1,2-α]benzimidazole (DAB-15) was examined on the model of arterial thrombosis developed in rats without concomitant pathology and in rats with experimental myocardial infarction. DAB-15 demonstrated high antithrombotic efficacy in modeled thrombosis of carotid artery in rats without the concomitant pathology surpassing that of the reference drugs acetylsalicylic acid and clopidogrel by 5.1 and 4.8 times, respectively. In rats with experimental noncoronary myocardial infarction, DAB-15 increased the thrombus formation time by 86.2% in comparison with experimental control level in non-treated rats with similar myocardial infarction.