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Synthetic approach to fused azasultams with 1,2,4-thiadi­azepine framework via base promoted protocols has been developed. 1H-Azole-2-carboxylates and N-(chloromethyl)-N-methylmethanesulfonamide were used as ambiphilic building blocks in the one-pot and two-step reaction sequences. Chemical behavior of the obtained azasultams in reactions with amines, hydrazine, DMFDMA, and NaBH4 was investigated. An enamino ketone derived from an azasultam was exploited in the synthesis of new pyrazole and pyrimidine heterocycles.

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)

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.

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.

An efficient synthesis of 7-membered Aza-sultams bearing heterofused amino-1,2,4-thiadiazepine framework have been developed. Functional group pairing strategy using ambiphilic building blocks such as 1H-azole-2-carbonitrile and N-(chloromethyl)-N-methylmethanesulfonamide in the two-step base-mediated reaction sequence was described. The synthetic utility of the obtained Aza-sultams was demonstrated by hydrolysis, reduction, and cross-coupling reactions. A cascade reaction involving β-enamine sulfonamide moiety within sultam ring in the synthesis of fused pyridine heterocycle has been investigated. It should be noted that β-enamine scaffolds among e-sultams have been first synthesized via the cyclization approach.

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.

Complex drugs based on C[Formula: see text] fullerence and pyrrole derivatives are promising for the development of antitumor and anti-inflammatory agents for use in targeted therapy, but have little efficiency in the synthesis of such complexes and have virtually no stable synthesis products with fullerene. The stability of the nanocomplex based on [60] PCBA and the intermediate compound based on “[Formula: see text]-pyrrole-2,5-dione” effective for the synthesis of targeted therapeutic agents was investigated by means of numerical calculations. The application of quantum-chemical methods in the Gaussian package establishes the stability of the nanocomplex at human body temperatures, the possibility of using such complexes for further study of the therapeutic properties of the individual components of the decomposition products of the nanocomplex.

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.

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 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 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 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.