Žurnal organičeskoj himii

The TGF-β signaling cascade is a regulator of cellular processes such as growth, division, differentiation, migration, invasion and apoptosis. Due to the deep involvement of this signaling pathway in the processes of carcinogenesis, participants in the cascade are promising oncology targets. Based on literature data, we have proposed a new structural class of TGF-β receptor inhibitors based on 2-aminopyrimidines. Two universal approaches to their synthesis have been proposed; the key transformation is the three-component Biginelli condensation aimed at the formation of a pyrimidine fragment. Using the developed synthetic approaches, 16 new compounds were obtained, for which antiproliferative activity in vitro was established against a number of tumor cell lines.

The transformations of dichloromethyladamantane and its derivatives in strongly acidic media have been studied. It has been established that the nitroxylation reaction is not accompanied by nitrolysis of the dichloromethyl group. A number of products of substitution of dichloromethyladamantane at the 3rd position were obtained under the conditions of generating a tertiary carbenium cation and it was found that the dichloromethyl group was retained in the structure of all products, which allows their further modification.

The properties of a representative number of previously unknown 2-(alkylsulfanyl)quinolines, obtained from aryl isothiocyanates, allene or acetylene carbanions, and methyl iodide, upon electron ionization (70 eV) have been studied for the first time. All the studied compounds form a stable molecular ion, which is clearly detected in the mass spectra. All studied quinolines are characterized by common decay patterns, including the formation of [M – H]⁺, [M – Me]⁺, and [M – HS]⁺ ions. The main effect on fragmentation is exerted by the nature of substituents at positions 3 and 4 of the pyridine cycle of quinolines. The molecular ion of 4-methyl-2-(methylsulfanyl)-3-(1H-pyrrol-1-yl)quinolines electron ionization undergoes rearrangement, which occurs both with the participation of a sulfur atom and with the participation of a carbon atom of the methyl group in the 4 position of the heterocycle. Ways of fragmentation of the formed ions of the studied 2-(alkylsulfanyl)quinolines are proposed based on the analysis of the mass spectra of daughter ions.

A new compound, 5-acetyl-2-amino-4-(2-chloro-5-nitrophenyl)-6-oxo-1-phenyl-1,4,5,6-tetrahydropyridine-3-carbonitrile, was synthesized by the reaction of 2-chloro-5-nitrobenzylidenemalononitrile with malononitrile and aniline. Subsequently, it was subjected to catalytic rearrangement in the presence of ethylenediamine and a second new compound, 4-(2-chloro-5-nitrophenyl)-6-oxo-2-(phenylamino)-1,4,5,6-tetrahydropyridine-3-carbonitrile, was obtained. The structure of the products was determined using NMR spectroscopy and X-ray diffraction analysis. A probable mechanism of the rearrangement reaction was proposed.

One-pot synthesis of 3,4-dihydropyrimidino[2,1-a]isoindol-6(2H)-one, an analog of the promising anti-cancer drug batracilin, has been developed. Both acylation of 1,3-diaminopropane with phthalic anhydride and followed by cyclocondensation took place while heating in toluene or ortho-xylene. The highest yield 76% of the target isoindolone was obtained by adding 1,3-diaminopropane to phthalic anhydride in toluene, while reverse order of mixing the reagents, decreases the yield to 60%. The reaction proceeds stepwise, through the formation of 2-(3-aminopropyl)carbamoyl)benzoic acid, which is converted to isoindolone upon heating with 68% yield.

Nitromethane reacts with phenylacetylene in the KOH(t-BuOK)/DMSO superbase media to form E- and Z-isomers of 4-benzyl-3-styryl-4,5-dihydroisoxazole-2-oxide, 2-benzyl-3-hydroxypropanonitrile and 1-benzyl-2-nitrocyclopropane.

1-Antipyryl-4-aroyl-5-methoxycarbonyl-1H-pyrrole-2,3-diones react with 1,3-diphenylguanidine to form 6-antipyryl-9-aroyl-8-hydroxy-2-imino-1,3-diphenyl-1,3,6-triazaspiro[4.4]non-8-en-4,7-diones, the structure of which was confirmed by 'H NMR and IR spectroscopy.

Condensation of previously synthesized 1,4-benzodioxane-2-carboxylic acid hydrazide with chloranhydrides of various arylcycloalkane-, as well as aerylterrahydropyrancarboxylic acids substituted in the aromatic ring, gave N,N′-diacyl-substituted hydrazines, which are cyclized under the action of phosphorus oxychloride to the corresponding 1,3,4-oxadiazolebenzodioxanes. The antihypoxic properties of the synthesized compounds were studied.

An effective method for the iodination of phenylacetylene in the presence of cadmium (II) acetate at room temperature in DMSO is described, and the ratio of reagents is optimized. Mercuration-demercuration with iodine and oxidative homecoupling reactions of iodoethylhybenzene were carried out.

By recyclization of 1,4,6-trimethyl-2-ethoxycarbonylmethylpyrimidinium iodide under the action of ethylhydrazine and 4,6-dimethylpyrimidinyl-2-acetic acid hydrazide, 1-ethyl-3-ethoxycarbonylmethyl-5-methyl-1,2,4-triazole and 5,7-dimethyl-3-ethoxycarbonyl-2-(4',6'-dimethyl-yrimidinyl-2')methylpyrazolol[1,5]-alpyrimidine were synthesized, respectively. Alkylation of 1-ethyl-3-ethoxycarbonylmethyl-5-methyl-1,2,4-triazole with various alkyl iodides yielded the corresponding N-alkyltriazolium salts, and reactions of triazolylacetic acid esters yielded their hydrazides. Based on the nuclear Overhauser effect (NOE), it was clearly demonstrated that alkylation occurs at the N-4 nitrogen atom of the triazole ring.