The reaction of monothiomalonamide with aromatic aldehydes and Meldrum’s acid in the presence of triethylamine yielded previously unknown stable Michael adducts – triethylammonium 5-[3-amino-1-(het)aryl-3-oxo-2-(thiocarbamoyl)propyl]-2,2-dimethyl-4-oxo-4H-1,3-dioxin-6-olates in 64–83

Triethylammonium (E)-2-oxo-1-(2-oxoindolin-3-ylidene)-2-phenylethane-1-thiolate, readily obtained from phenacyl thiocyanate and isatin, undergoes efficient S-alkylation with alkyl halides in refluxing DMF. When ethyl 4-chloroacetoacetate is employed, the reaction affords (E)-3-[2-oxo-1-(2-oxopropyl)thio-2-phenylethylidene]indolin-2-one via in situ Krapcho decarboxylation of the intermediate β-keto ester; the structure was confirmed by X-ray crystallography. Quantum chemical calculations (ωB97X-3c/CPCM) reveal that the (E)-isomer of the starting thiolate is thermodynamically favored by 18 kJ/mol over the (Z)-form in EtOAc. In silico ADMET profiling and protein-ligand docking studies indicate favorable bioavailability parameters and potential interactions with targets such as stromelysin-1 (MMP-3), FABP4, and PPAR-γ, suggesting possible anti-inflammatory and antidiabetic applications. Under laboratory conditions, the starting thiolate exhibits significant protective (antidote) activity against the herbicide 2,4-D in sunflower seedlings, increasing hypocotyl and root lengths by up to 126 and 154

The aim of this work was to prepare new heterodimeric molecules containing pharmacophoric fragments of 3-cyanoquinoline/3-aminothieno[2,3-b]pyridine/3-aminothieno[2,3-b]quinoline on one side and phenothiazine on the other. The products were synthesized via selective S-alkylation of readily available 2-thioxo-3-cyanopyridines or -quinolines with N-(chloroacetyl)phenothiazines, followed by base-promoted Thorpe–Ziegler isomerization of the resulting N-[(3-cyanopyridin-2-ylthio)acetyl]phenothiazines. We found that both the S-alkylation and the Thorpe–Ziegler cyclization reactions, when conducted with KOH under heating, were accompanied to a significant extent by a side reaction involving the elimination of phenothiazine. Optimization of the conditions (0–5 °C, anhydrous N,N-dimethylacetamide and NaH or t-BuONa as non-nucleophilic bases) minimized the side reaction and increased the yields of the target heterodimers. The structures of the products were confirmed by IR spectroscopy, 1H, and 13C DEPTQ NMR studies. It was demonstrated that the synthesized 3-aminothieno[2,3-b]pyridines can be acylated with chloroacetyl chloride in hot chloroform. The resulting chloroacetamide derivative reacts with potassium thiocyanate in DMF to form the corresponding 2-iminothiazolidin-4-one; in this process, phenothiazine elimination does not occur, and the Gruner–Gewald rearrangement product was not observed. The structural features and spectral characteristics of the synthesized 2-iminothiazolidin-4-one derivative were investigated by quantum chemical methods at the B3LYP-D4/def2-TZVP level. A range of drug-relevant properties was also evaluated using in silico methods, and ADMET parameters were calculated. A molecular docking study identified a number of potential protein targets for the new heterodimers, indicating the promise of these compounds for the development of novel antitumor agents.

The reaction of ethyl 3-aryl-2-cyanoacrylates (arylmethylene cyanoacetates) with N1,N3-disubstituted malonamides in the presence of Et3N under mild conditions (absolute EtOH, 25°C) produces new stable Michael adducts, ethyl 3-aryl-2-cyano-5-oxo-5-(N-R-amino)-4-(N-R-carbamoyl)pentanoates, in 57–95

The design of molecular hybrids based on biologically active molecules is one of the most prominent strategies in modern drug design. Molecular hybridization involves combining two or more pharmacophore fragments into a single molecule, resulting in synergistic effects and combination therapy within a single multifunctional agent. These hybrids often exhibit more specific and potent activity compared to classical drugs. In this study, we developed a method for synthesizing new molecular hybrids of 2-iminothiazoline/3-cyanoquinoline and 2-iminothiazoline/3-aminothieno[2,3-b]quinoline through the reaction of N-(3-aryl-4-phenylthiazol-2(3H)-ylidene)2-chloroacetamides with 4-aryl-2-thioxo-1,2,5,6,7,8-hexahydroquinoline-3-carbonitriles. The starting 4-aryl-2thioxo-1,2,5,6,7,8-hexahydroquinoline-3-carbonitriles were synthesized by reacting aromatic aldehydes, cyanothioacetamide, and 4-(cyclohex-1-en-1-yl)morpholine. Meanwhile, the novel alkylating agents, N-(3-aryl-4phenylthiazol-2(3H)-ylidene)-2-chloroacetamides, were prepared in 66-73 % yield via a two-step process: 1) Heterocyclization of alpha-thiocyanatoacetophenone with primary aromatic amines in the presence of aqueous HCl; 2) Subsequent reaction of the resulting 3-aryl-4-phenylthiazol-2(3H)-imines with chloroacetyl chloride in anhydrous benzene. The target molecular hybrids - 2-iminothiazoline/3-cyanoquinoline and 2-iminothiazoline/3-aminothieno [2,3-b]quinoline - were isolated in yields of 64-93 % and 63-92 %, respectively. The structures of the new hybrids were thoroughly characterized using X-ray diffraction analysis, FTIR spectroscopy, and NMR spectroscopy, including 2D NMR techniques (1H-13C HSQC, 1H-13C HMBC). An unusual feature in the FTIR spectra - the absence of nu(C--O) absorption bands above 1600 cm-1 - was attributed to conjugation between the carbonyl group and either the 2-iminothiazoline C--N fragment or the thieno[2,3-b]quinoline moiety. These findings were further supported by quantum-chemical calculations. Both computational and X-ray data indicated that the most stable conformation for 3-amino-4-aryl-N-(3-aryl-4-phenylthiazol-2(3H)-ylidene)-5,6,7,8-tetrahydrothieno[2,3b]quinoline-2-carboxamides is the s-cis conformation, stabilized by an intramolecular hydrogen bond between the NH2 protons and the C--O oxygen. Additionally, six new compounds demonstrated a noticeable antidote effect against the herbicide 2,4-D in field experiments on sunflower seedlings.

1,3-Dithiocyanatoacetone was prepared by reaction of 1,3-dichloroacetone with potassium thiocyanate in ethanol in almost quantitative yield. In contrast to the NMR spectra recorded in acetone-d6, NMR spectra of 1,3-dithiocyanatoacetone in DMSO-d6 solution revealed the presence of the enol form. The keto-enol tautomerism is discussed and the structure of main conformers and tautomers of dithiocyanatoacetone and its acid hydrolysis product, S-[(2-oxo-2,3-dihydro- 1,3-thiazol-4-yl)methyl]thiocarbamate, was investigated by quantum chemical methods. The vibrational spectra were calculated and found to be in a good agreement with the experimental FT-IR spectra. The structure of 1,3-dithiocyanatoacetone and S-[(2-oxo-2,3-dihydro-1,3-thiazol-4-yl)methyl]thiocarbamate was studied by X-ray diffraction analysis. Molecular docking and bioavailability parameters calculations showed the potential of the compounds as carbonic anhydrase inhibitors.

New [1,2]dithiolo[3,4-b]pyridine-5-carboxamides were synthesized through the reaction of dithiomalondianilide (N,N′-diphenyldithiomalondiamide) with 3-aryl-2-cyanoacrylamides or via a three-component reaction involving aromatic aldehydes, cyanoacetamide and dithiomalondianilide in the presence of morpholine. The structure of 6-amino-4-(2,4-dichloro- phenyl)-7-phenyl-3-(phenylimino)-4,7-dihydro-3H-[1,2]dithiolo[3,4-b]pyridine-5-carboxamide was confirmed using X-ray crystallography. To understand the reaction mechanism in detail, density functional theory (DFT) calculations were performed with a Grimme B97-3c composite computational scheme. The results revealed that the rate-limiting step is a cyclization process leading to the closure of the 1,4-dihydropyridine ring, with an activation barrier of 28.8 kcal/mol. Some of the dithiolo[3,4-b]pyridines exhibited moderate herbicide safening effects against 2,4-D. Additionally, ADMET (Absorption, Distribution, Metabolism, Excretion, Toxicity) parameters were calculated and molecular docking studies were performed to identify potential protein targets.

A simple approach was proposed to the synthesis 5-benzoyl-2-imino-4-thiazolines by the reaction of α-thiocynatoacetophenone with various aryl amines and triethyl orthoformate. Structure of the prepared compounds was confirmed by IR spectrophotometry and NMR spectroscopy, including two-dimensional HMBC and HSQC experiments.

A coordination compound of copper(II) with succinic acid was obtained by electrochemical synthesis in media of various compositions. The samples were characterized by methods of quantitative analysis, ESR and IR spectroscopy, synchronous thermal analysis. The vibrational frequencies of copper(II) succinate were calculated by using DFT and the experimental IR spectra were interpreted on the basis of the results. Micro-sized copper(II) oxide fibers were obtained by thermal decomposition of synthesized samples. It was shown that the use of the water–dimethyl sulfoxide system with a volume ratio 1:1 is optimal to achieve the formation of moderately aggregated particles with a distinct filamentous morphology.

Data on the synthesis methods, chemical transformations, and biological activity of 4H-3,1-benzoxazines and their dihydro derivatives, including coordination compounds of the dihydro derivatives with transition metals, are systematized and analyzed.

Iodination of 2-(4-arylthiazole-2-yl)acetonitriles in DMF proceeds with the formation of previously undescribed 2,3-bis(4-aryl-1,3-thiazole-2-yl)but-2-enedicarbonitriles as a mixture of E- and Z-isomers. The latter were alternatively prepared by the reaction of cyanothioacetamide, α-bromoketones and iodine in DMF. Structure of the key compounds was proven by means of single crystal X-ray diffraction analysis.

The structure, antioxidant and neuroprotective properties of lithium comenate (lithium 5-hydroxy-4-oxo-4H-pyran-2-carboxylate) were studied. Lithium comenate was obtained by reacting comenic acid (H2Com) with lithium hydroxide in an aqueous solution. The structure of lithium comenate was confirmed via thermal analysis, mass spectrometry, IR, NMR and UV spectroscopy. The crystal structure was studied in detail via X-ray diffraction. The compound crystallized in a non-centrosymmetric space group of symmetry of the orthorhombic system Pna21 in the form of a hydrate, with three water molecules entering the first coordination sphere of the cation Li+ and one molecule forming a second environment through non-valent contacts. The gross formula of the complex compound was established [Li(HCom)(H2O)3]·H2O. It has been established that lithium comenate has a pronounced neuroprotective activity under the excitotoxic effect of glutamate, increasing the survival rate of cultured rat cerebellar neurons more than two-fold. It has also been found that the pre-stress use of lithium comenate at doses of 1 and 2 mg/kg has an antioxidant effect, which is manifested in a decrease in oxidative damage to the brain tissues of mice subjected to immobilization stress. Based on the data available in the literature, we believe that the high neuroprotective and antioxidant efficacy of lithium comenate is a consequence of the mutual potentiation of the pharmacological effects of lithium and comenic acid.

Meconic, comenic, chelidonic, and kojic acids are the main representatives of gamma-pyronic acids. It was found that comenic acid has a neuroprotective effect, and chelidonic acid has a pronounced anti-inflammatory effect. The neuroprotective effect of meconic acid has not been explored. The aim of this study was to investigate the neuroprotective potential of meconic acid on an in vitro ischemic stroke model, as well as on the basis of its physicochemical properties. A primary neuro-glial culture was obtained from the cerebellum of 7- to 8-day-old Wistar rats by mechanical dissociation. The protective effect of meconic acid on the culture of cerebellar neurons was studied using a model of glutamate toxicity and oxygen–glucose deprivation. The antioxidant activity of meconic acid was studied by quantum mechanical calculations and experimentally in the citrate-phosphate-luminol model system by chemiluminescence analysis. The chelating properties of meconic acid with respect to Fe3+ in solutions were studied by the Job’s method. Meconic acid has been found to have a protective effect on in vitro models of ischemia. It caused a decrease in the level of intracellular calcium and restoration of the membrane potential of mitochondria in the culture of cerebellar neurons under glutamate exposure and an increase in the percentage of living cells under oxygen–glucose deprivation. Meconic acid had a high calculated antioxidant potential, as was confirmed experimentally. With an increase in pH of the medium, a stepwise binding of meconic acid with Fe3+ occurred with the formation of complexes of different ligand/metal ratios. At physiological pH, the resulting complex had a composition with the ratio 1 : 3. The revealed antioxidant, chelating, and cytoprotective effects of meconic acid provide a basis for further study of the possible neuroprotective properties of this compound in experiments in vivo; the data on its physicochemical properties can be useful for the synthesis and study of new coordination compounds based on this acid.

The paper presents the results of studying the electrochemical characteristics and long-term stability of MA-41 membranes on the surface of which poly-N,N-diallylmorpholinium bromide was applied. The deposition of a polyelectrolyte on the membrane surface leads to an increase in the limiting current from 0.8 to 1.1 mA/cm2. The comparison of the experimental and theoretically calculated values of the limiting current density allows us to conclude that the modification of the membrane surface by poly-N,N-diallylmorpholinium bromide does not lead to the formation of a continuous polyelectrolyte film on the surface, but its fixation occurs due to the sorption of macromolecules on the surface of the ion-exchanger particles. To quantify the rate of the water dissociation reaction at the membrane/solution interface, the method of electrochemical impedance was used, which makes it possible to compare the rate constants of the water dissociation reaction for different membranes, assuming that the reaction is described by the Gericher impedance. It is shown that modification of the MA-41 membrane surface leads to a decrease in the rate of the water dissociation reaction in the current range i = 1.5–4ilim by a factor of 2–6. The reduction in water dissociation reaction rate is attributed to the substitution of catalytically active secondary and tertiary amino groups in the surface layer of the pristine membrane by stable heterocyclic ammonium bases of poly-N,N-diallylmorpholinium. The study of the long-term stability of the resulting membrane showed that when the membrane is polarized with a current equal to twice the limiting current, the desorption of the modifier occurs within 25 h, and the properties of the membrane become close to those of the unmodified MA-41 membrane. It was shown that the electrochemical impedance method can be used as a very sensitive method for studying the long-term stability of ion-exchange membranes.

A new series of thienopyridine derivatives, namely N-(thieno[2,3-b]pyridin-3-yl)aminoalcohols, was obtained by a cascade deacylation/alkylation reaction of 3-aminothieno[2,3-b]pyridine ketones. An alternative approach to the synthesis of these compounds by alkylation of 3-aminothienopyridines unsubstituted at position 2 with diols was proposed.

5-Amino-3-(cyanomethyl)-1H-pyrazole-4-carbonitrile enters into condensation reactions with β-diketones and dibenzalacetone to form 2-(cyanomethyl)pyrazolo[1,5-a]pyrimidine-3-carbonitrile derivatives. The reaction with cyanoguanidine in an acid medium leads to the formation of 2,4-diamino-7-(cyanomethyl)pyrazolo[1,5-a][1,3,5]triazine-8-carbonitrile. Structure of the obtained compounds was confirmed by spectral data, as well as the results of a quantum chemical study of possible reaction routes for the reaction of 5-amino-3-(cyanomethyl)-1H-pyrazole-4-carbonitrile with benzoyltrifluoroacetone. Bioavailability parameters were predicted for the obtained products in silico, and possible protein targets were predicted by protein-ligand docking.

The spectral characteristics of dithiomalondianilide (N,N′-diphenyldithiomalonodiamide) were studied, and the dissociation constant was determined by potentiometric titration. Quantum-chemical methods at the B3LYP-D3BJ/6-311+G (2d,p) level were used to calculate the molecular geometry and vibrational spectra of the most stable tautomeric forms of dithiomalondianilide. The bioavailability parameters were calculated, and possible protein targets were predicted by the protein ligand docking method.

The reaction of 2-amino-1,1,3-tricyanopropene (malononitrile dimer) with isothiocyanates leads to 1-substituted 4,6-diamino-2-thioxo-1,2-dihydropyridine-3,5-dicarbonitriles or 4,6-diamino-2-(phenylimino)-2 H -thiopyran-3,5-dicarbonitrile, depending on the conditions. Quantum-chemical modeling of the IR spectra and reaction routes for the synthesized compounds was carried out. In silico predictive analysis of potential protein targets, compliance with bioavailability criteria, and ADMET parameters was performed.