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Ability of C 60 fullerenes to scavenge free radicals and of multy-kinase inhibitor pyrrole derivative to regulate production and activation of immune cells producing damaging free radicals, could be a rationale of hybrid nanocomplex synthesis based on them. So, therapeutic potential of nanocomplex 3-{[4-chloro-1-(4-chlorobenzyl)-2,5dioxo-2,5-dihydro-1H-pyrrole-3-yl]amino}phenyl 4-[6, 6]phenyl-C61-butanoate (C60-MI-3OH) under rat acute ulcerative colitis has been investigated.C60-MI-3OH reduced systemic inflammation under acute colitis, as evidenced by normalization of the leukocytes count in blood due to the lowering of neutrophilic granulocytes and monocytes number with simultaneous reduction of colon damage area. C60-MI-3OH abolishes development of anemia under acute colitis probably due to the decreased volume of hemorrhages as a result of intensifying the processes of colon wall healing and erythropoiesis stimulation.Complexation of pyrrole derivative having multi-kinase inhibitory activity with C60-fullerenes could potentiate the efficacy of the first one and allow the complex to be applied in low dose (0.2 mg/kg)

This article reports on the reaction of 2-hetaryl-2-(furanyl-2-ylidene)acetonitriles with aromatic amines as N-nucleophiles. 2-Hetaryl-2-(furanyl-2-ylidene)acetonitriles represent versatile building blocks in syntheses of ω-(N-aryl)alkyl substituted heterocycles due to the presence of 1,3-bielectrophilic acrylonitrile fragment functionalized with unsaturated heterocyclic ring and nucleophilic azaheterocyclic moiety. The carbonyl group masked within the N-arylpyrrolidinylidene fragment which undergoes a ring opening through the reaction with nucleophiles. So, a method for the synthesis of 2-hetaryl-6-hydroxy-3-(arylamino)hex-2-enenitriles and 2-hetaryl-2-(N-arylpyrrolidin-2-ylidene)acetonitriles has been developed by us. The proposed scheme is based on the available reagents using. As a result of Michael addition, the aromatic amines to 2-hetaryl-2-(furanyl-2-ylidene)acetonitriles followed by ring transformations has formed two types of products, depending on the reaction conditions. The reaction of substituted furanylylideneacetonitriles with aromatic amines proceeds in good to high yields affording the corresponding 3-(arylamino)hex-2-enenitriles and 2-(N-arylpyrrolidin-2-ylidene)acetonitriles derivatives. The stereochemistry of the ring-opening reaction follows the rules of a classical SN2 mechanism. The resulting linear products can be cyclized to 2-hetaryl-2-(furanyl-2-ylidene)acetonitriles in high yields by treatment with the catalytic amount of acid or the equimolar amount of aromatic amines. Under these conditions 2-hetaryl-6-hydroxy-3-(arylamino)hex-2-enenitriles arising from reaction gives the ring closure. Since both ring-opening and cyclisation occur with fixed stereochemistry the reaction appears a valuable modification to the preparation of acetonitriles derivatives.

The interaction of (2-aryl-5-(hydroxyalkylamino)-1,3-oxazol-4-yl)phosphonates with hydrogen chloride, hydrogen iodide and hydrogen thiocyanate in anhydrous medium led to formation of new phosphorylated peptidomimetics containing C-terminal ω-haloalkyl and ω-thiocyanoethyl residues.

Pyrrole derivatives (PDs) chloro-1-(4-chlorobenzyl)-4-((3-(trifluoromethyl)phenyl)amino)-1H-pyrrole-2,5-dione (MI-1) and 5-amino-4-(1,3-benzothyazol-2-yn)-1-(3-methoxyphenyl)-1,2-dihydro-3H-pyrrole-3-one (D1) were synthesised as inhibitors of several protein kinases including EGFR and VEGFR. The aim of the study was to reveal the exact mechanisms of PDs' action EGFR and VEGFR are involved in. We observed, that both PDs could bind with EGFR and VEGFR and form stable complexes. PDs entered into electrostatic interactions with polar groups of phospholipid heads in cell membrane, and the power of interaction depended on the nature of PD radical substituents (greater for MI-1 and smaller for D1). Partial intercalation of MI-1 into the membrane hydrophobic zone also occurred. PDs concentrations induced apoptosis in malignant cells but normal ones had different sensitivity to those. MI-1 and D1 acted like antioxidants in inflamed colonic tissue, as evidenced by reduce of lipid and protein peroxidation products (by 43-67%) and increase of superoxide dismutase activity (by 40 and 58%) with restoring these values to control ones. MI-1 restored reduced haemoglobin and normalised elevated platelets and monocytes in settings of colorectal cancer, whereas D1 normalised only platelets. Thus, MI-1 and D1 could be used as competitive inhibitors of EGFR and VEGFR and antioxidants, which might contribute to realisation of their anti-inflammatory, proapoptotic and antitumor activity.

The photoconductive and photovoltaic properties of fi lm composites based on the new oligomer polyepoxypropylpyridobenzothiazole were compared with the known poly-N-epoxypropylcarbazole, which contains the squarylium dye as a photoconductivity sensitizer. It was found that these composites have hole-type photoconductivity, and the internal photoelectric effect is determined by the photogeneration of charge carriers from dye molecules and by transport of the holes along the donor fragments of the polymer matrix. The photoconductivity and photovoltaic response increase in the transition to the new oligomer with the more effi cient conjugation system in the donor fragments.

It was found that film composites of the copolymer of styrene with octyl methacrylate with additions of the monomers of pyrido[2,1-b]benzothiazole derivatives have hole-type photoconductivity while the internal photoelectric effect in this medium is determined by the photogeneration of charge carriers from the monomers and transfer of nonequilibrium charge carriers through these monomers. In transition to a monomer with a more efficient conjugation system the photoconductivity and photovoltaic response are increased.

Synthetic approaches for the preparation of 6-amino-5-hetarylpyrimidine derivatives by the ring transformation reaction of 2-hetaryl-2-(tetrahydro-2-furanyliden)acetonitriles with amidines have been developed. Some of 2,6-diamino-5-(1,3-benzothiazol-2-yl)pyrimidines were found to exhibit modest inhibitory activity against human dihydrofolate reductase. Molecular docking was performed to evaluate the binding mode of compounds of this series in the enzyme’s active site.

The photovoltaic and photoconductive properties of film composites of a copolymer of styrene with octyl methacrylate and additions of the monomer (Z)-2-(4-methylthiazol-2-yl)-2-(pyrrolidin-2-ylidene)acetonitrile (HL) and complexes of NiL2, CoL2, and CuL2 were investigated. It was established that these composites have hole-type photoconductivity while the inner photoeffect is determined by photogeneration of charge carriers from the HL monomers and by transport of nonequilibrium charge carriers among these monomers. The photovoltaic response increases with the metal complexes in the following order: CuL2, NiL2, CoL2.

4-Amino-3-chloro-1H-pyrrole-2,5-dione derivatives were designed and synthesized as potential tyrosine kinase inhibitors. One of them has been shown to inhibit growth of cancer cell lines and in vivo tumors. To determine the impact of side groups on biological activity the ability of different 4-amino-3-chloro-1H-pyrrole-2,5-diones to interact with ATP-binding domains of growth factor receptors and with model cell membranes were aimed to be discovered. The methods of molecular docking, short-molecular dynamics (in silico) and non-steady cyclic current-voltage characteristics (in vitro) were used. Five 4-amino-3-chloro-1H-pyrrole-2,5-diones were synthesized from 3,4-dichloro-1H-pyrrole-2,5-diones. All of them demonstrated the potential ability to form complexes with ATP-binding domains of EGFR and VEGFR2. These complexes were more stable compared to those with ANP. 4-Amino-3-chloro-1H-pyrrole-2,5-diones while interact with different bilayer lipid membranes caused an increase of their specific conductance and electric capacity, demonstrating the certain disturbance in lipid packing. Obtained data allowed us to suggest that proposed chemicals can interact with the surface of lipid bilayer, do likely intercalate into the membrane and form stable complexes with EGFR and VEGFR2. So, the prospect of developed chemicals to be effective EGFR and VEGFR2 inhibitors and therefore realize antitumor activity was concluded.

New method was developed for the synthesis of 2-hetaryl-2-(1-R-pyrrolidin-2-ylidene)acetonitriles by using a three-component condensation of hetarylacetonitrile, phosphorus oxychloride, and 1-R-pyrrolidin-2-one. This method is applicable to the synthesis of β-enaminonitriles containing azoles and six-membered azaheteroaromatic rings at the α-position relative to the nitrile group.

This microreview is devoted to the recent developments in the synthesis of 5-imino- and 5-oxothiazolo-[3,2-a]pyridines. General synthetic strategy toward fused thiazolopyridine ring system utilizing azahetaryl precursors is discussed.

The selective and sensitive hyphenated technique for Pd(II) fluorescence and spectrophotometric determination was proposed. The procedure was based on preliminary solid-phase extraction of [PdCl4]2− onto silica modified with quaternary ammonium salts, with the subsequent elution from the surface by 2,6-diamino-1- N-methylpyrimidine solution and measurement of the fluorescence intensity. The luminescence enhancement effect of 2,6-diamino-1- N-methylpyrimidine in the presence of Pd(II) due to the complex formation was applied to the development of sorption-spectroscopic techniques for detecting trace amounts of palladium in solution.

The reaction of 2-hetaryl-2-(tetrahydro-2-furanyliden)acetonitriles with substituted acetonitriles as C-nucleophiles has been investigated and the mechanism of the reaction has been suggested. A base promoted Michael addition of the substituted acetonitriles to 2-hetaryl-2-(tetrahydro-2-furanyliden)acetonitriles followed by ring transformations has provided novel convenient synthetic methods to nitrogen bridgehead fused cyanopyridines bearing hydroxypropyl side chain. The structures of obtained compounds have been established based on NMR spectroscopy investigation and X-ray diffraction data.

The ring opening reactions of 2-hetaryl-2-(tetrahydro-2-furanylidene)acetonitriles with α-, β-, γ-, e-amino acids and alkyl esters of α-amino acids as N-nucleophiles have been investigated. New functionalized amino acid derivatives containing the heterocyclic moiety have been obtained and their reactions with electrophilic and nucleophilic agents have been studied.

The reactions of 2-(2-hetaryl)-2-(tetrahydrofuran-2-ylidene)acetonitriles with conformationally rigid and heterocyclic tertiary amines were investigated. Compounds with bipolar structures were obtained: 1-cyano-1-(2-hetaryl)-5-(pyridinium-1-yl)-1-penten-2-olates and 5-(4-aza-1-azoniobicyclo[2.2.2]oct-1-yl)-1-cyano-1-(2-hetaryl)pent-1-en-2-olates.

The reaction of 2-hetaryl-2-(tetrahydrofuran-2-ylidene)acetonitriles and 6-chloro-2-(2-hetarylidene)-3-oxohexanenitriles with amines was studied. It was shown that the reaction of primary aliphatic amines with 6-chloro-2-(2-hetarylidene)-3-oxohexanenitriles takes place through a stage involving the formation of 2-hetaryl-2-(tetrahydrofuran-2-ylidene)acetonitriles followed by opening of the furanylidene fragment of the latter and the formation of 2-(2-hetaryl)-6-hydroxy-3-(R-amino)-2-hexenenitriles.

International audience; We report here an efficient and easily reproducible two-step approach to heterocycle-substituted amino-pyrazoles from heterocyclic acetonitriles and their unprecedented subsequent transformations to fully substituted pyrazoles. Such transformations include regioselective derivatization from polyamino derivatives, formation of tetracyclic compounds in up to 45% overall yield, and deaminative transformations through diazotization, followed by arylation through Suzuki–Miyaura cross-coupling and C–H activation, providing arylated pyrazoles in up to 71% yield over four steps. This strategy allows the swift introduction of significant molecular complexity to a range of scaffolds.

The reactions of 2-hetaryl-2-(tetrahydro-2-furanyliden)acetonitriles with 1,3-N,N-binucleophiles have been investigated. The mechanisms of the reactions have been discussed. Domino reactions of 2-hetaryl-2-(tetrahydro-2-furanyliden)acetonitriles with amidines can provide an efficient access to 3-[2-substituted 6-amino-5-hetaryl-4-pyrimidinyl]-1-propanols.

The reaction of azolylacetonitriles with γ-chlorobutyryl chlorides gave the corresponding 2-(1-R-1,3-di- hydro-2H-benzimidazol-2-ylidene)-, 2-(1,3-benzothiazol-2-ylidene)-, and 6-chloro-2-(4-methylthiazol-2-ylidene)-3-oxohexanenitriles. A study of the intramolecular cyclization of 2-(quinazolin-2-ylidene)-3-oxo-6-hexanenitriles and -heptanenitriles has led to the development of an efficient method for the preparation of 2-(quinazolin-2-yl)-2-(tetrahydrofuran-2-ylidene)acetonitriles. The (Z,E)-isomerism of the synthesized 2-hetaryl-2-(tetrahydrofuran-2-ylidene)acetonitriles was studied.

The reaction of 2-hetaryl-2-(tetrahydro-2-furanylidene)acetonitriles with a electrophilic reagent (anisaldehyde) was studied. It was shown that condensation of the latter with 2-(4-oxo-3,4-dihydro-2-quinazolyl)- and 2-(1H-benzo[d]imidazol-2-yl)-2-(tetrahydro-2-furanylidene)acetonitriles in the presence of secondary amines or acids takes place with elimination of the furan fragment and the formation of 3-aryl-2-(4-oxo-3,4-dihydro-2-quinazolinyl)- and 2-(1H-benzo[d]imidazol-2-yl)acrylo-nitriles.

The luminescence spectral properties of 3-pyridyl-7-hydroxy-2-iminocoumarin and 3-(2-methylthiazole)-7-hydroxy-2-iminocoumarin were studied in ethanol solutions at different values of pH and also in other solvents differing in polarity. In their ethanol solutions, the compounds can exist as neutral molecules, anions, cations, and zwitterions. The spectral properties and geometry were studied for all possible forms of these compounds by the INDO/S quantum-chemical method.

The spectral, luminescent, and lasing properties of four derivatives of 7-hydroxycoumarin: 7-hydroxy-3-(4-methylthiazolyl)-coumarin (CI), 3-(4-methylthiazolyl)-2-oxocoumarin-furan-2-carboxylate (CII), 3-(4-(benzo[1,3]dioxolyl)-thiazolyl)-2-oxocoumarin-furan-2-carboxylate (CIII), and 3-(4-(benzo[1,3]dioxolyl)-thiazolyl)-2-hydroxycoumarin (CIV), as well as of their protolytic forms, are studied experimentally and theoretically by the INDO/S method. The luminescence quantum yield of the CIII and CIV compounds, having bulky substituents at position 3, is shown to strongly depend on the polarity of a solvent. It is suggested that, in polar solvents, these substituents are displaced out of the plane of the skeleton of the electronically excited molecule. The quantum-chemical calculations of such structures confirmed their weak fluorescence ability due to intense intersystem crossing. The lasing ability of the protolytic forms of the compounds considered is studied. The reason for the absence of lasing for the neutral compounds is discussed.

The reaction of 4-oxo-3,4-dihydroquinazolyl-and benzimidazolylacetonitriles with 2-chloro-2-quinolinecarbaldehydes and 1-aryl-5-chloro-3-methyl-1H-pyrazole-4-carbaldehydes gave the corresponding 3-(2-chloro-3-quinolyl)-2-(4-oxo-3,4-dihydro-2-quinazolyl)-2-propenenitriles and 3-(1-aryl-5-chloro-3-methyl-1H-4-pyrazolyl)-2-hetaryl-2-propenenitriles. Intramolecular cyclization of these compounds gives 15-oxo-15H-benzo[6,7][1,8]naphthyridino[2,1-b]quinazoline-6-carbonitriles, 1-aryl-3-methyl-11-oxo-1,11-dihydropyrazolo[4′,3′:5,6]pyrido[2,1-b]quinazoline-5-carbonitriles, and 1-aryl-3-methyl-1H-benzo[4,5]imidazo[1,2-a]pyrazolo[4,3-e]pyridine-5-carbonitriles.

3-(2-Pyridyl)coumarins were prepared by reaction of substituted salicylaldehydes and 2-pyridylacetonitrile. Benzylation, acylation, and aminomethylation of 7-hydroxy-3-(2-pyridyl)coumarin was studied.

3-(2-Quinolyl)- and 3-(5-carbethoxyfuryl-2)coumarins were prepared by reaction of substituted salicylaldehydes and hetarylacetonitriles. Alkylation and acylation of 3-hetaryl-7-hydroxycoumarins were studied.

The interaction of 4-oxo-3,4-dihydroquinazolinyl- and benzimidazolylacetonitriles with 2,6-dihalobenzaldehydes leads to 3-(2,6-dihalophenyl)-2-(4-oxo-3,4-dihydro-2-quinazolinyl)acrylonitriles and 2-(1H-benzo[d]imidazol-2-yl)-3-(2,6-dihalophenyl)acrylonitriles respectively. As a result of intramolecular cyclization of these nitriles 4-halo-12-oxo-12H-quino[2,1-b]quinazoline-6-carbonitriles and 4-halobenzo[4,5]imidazo[1,2-a]quinoline-6-carbonitriles respectively are formed.

2-(4-Oxo-3,4-dihydro-2-quinazolinyl)acetonitriles have been obtained by the interaction of α-cyanoethylthioiminoacetate with substituted anthranilic acids. Prototropy became apparent in the series of synthesized compounds. Reactions of the 2-(4-oxo-3,4-dihydro-2-quinazolinyl)acetonitriles have been carried out with (hetero)aromatic aldehydes leading to the formation of 3-aryl-2-(4-oxo-3,4-dihydro-2-quinazolinyl)acrylonitriles.

The base promoted Michael addition of substituted acetonitriles to 2-hetaryl-2-(tetrahydro-2-furanyliden)acetonitriles followed by ring transformations provides a novel and convenient synthetic access to nitrogen bridgehead fused cyanopyridines bearing a hydroxypropyl side chain.

The reaction of substituted salicylaldehydes with 2-benzimidazolyl- and 2-benzothiazolylacetonitriles gives the corresponding 3-hetarylcoumarins. The alkylation, acylation, and aminomethylation reactions of these 7-hydroxy-substituted hetero isoflavonoid analogs has been studied.

The reactions of 2-(2-hetaryl)-2-(tetrahydrofuran-2-ylidene)acetonitriles with conformationally rigid and heterocyclic tertiary amines were investigated. Compounds with bipolar structures were obtained: 1-cyano-1-(2-hetaryl)-5-(pyridinium-1-yl)-1-penten-2-olates and 5-(4-aza-1-azoniobicyclo[2.2.2]oct-1-yl)-1-cyano-1-(2-hetaryl)pent-1-en-2-olates.

The ring opening reactions of 2-hetaryl-2-(tetrahydro-2-furanylidene)acetonitriles with α-, β-, γ-, e-amino acids and alkyl esters of α-amino acids as N-nucleophiles have been investigated. New functionalized amino acid derivatives containing the heterocyclic moiety have been obtained and their reactions with electrophilic and nucleophilic agents have been studied.

The title substrates (I) and (VI) react with amidines, either as carbonates or nitrates, to produce different types of pyrimidine structures.