Suchergebnisse

Heterocyclic compounds have an extremely important practical application, since many heterocycles are the basis of the most valuable medicinal substances, both natural (vitamins, enzymes, alkaloids, etc.) and synthetic biologically active compounds. The work mainly considers the most relevant directions for various purposes drugs search by modifying known bioactive natural, organoelement and framework compounds with 1,2-azole, oxazole, oxadiazole, thiazole, triazole, pyridine, pyrimidine heterocycles over the past 10 years. Chemical modification makes it possible to increase the water solubility of the compounds, which is important when choosing the pathways for the most rational drug introduction into the body, to reduce the toxicity of the corresponding substances, to increase the breadth of the therapeutic action, and also to give new valuable medicinal properties, thus significantly expanding their application in medicine and agriculture.

Curcumin is a chemical compound with antioxidant properties as well as strong anti-inflammatory, antiviral, analgesic, antimicrobial and antitumor effect, contained in the tuberous rhizomes of the turmeric plant (Curcuma longa). Curcumin derivatives are being intensively studied as potential drugs – antitumor drugs for the treatment of certain forms of cancer. The presence of reactive functional groups makes curcumin a convenient starting compound for the further chemical modification. The esters of curcumin and 5-phenylisoxazole-3-carboxylic acid, 5-(p-tolyl)isoxazole-3-carboxylic acid, 4,5- dichloroisothiazole-3-carboxylic acid and adduct of 5-(p-tolyl)isoxazol-3-carbaldehyde with curcumin were synthesized. Esters were obtained by acylation of curcumin with heterocycle-containing carboxylic acid chloride in diethyl ether in the presence of triethylamine. The IR and NMR spectra of the obtained compounds are described.

Various adamantane derivatives were obtained by the condensation of rimantadine with substituted hydroxy-benzaldehydes, esters and ethers based on them, as well as 1,2-azole-3-carbaldehydes, followed by reduction. Further acylation of derivatives with active amino and hydroxy groups yielded compounds containing two 1,2-azole fragments in one molecule.

Based on esters of nicotinic and isonicotinic acids with hydroxybenzaldehydes, a series of functionally substituted derivatives containing isoxazole and isothiazole heterocycles in the molecule have been synthesized. Azomethines were obtained by condensation of nicotinates and isonicotinates with p-bromoaniline and m-aminophenol, which have been reduced with sodium triacetoxyborohydride to give the corresponding amines. Acylation of amino derivatives of nicotinates and isonicotinates with 5-arylisoxazole- and 4,5-dichloroisothiazolecarbonyl chlorides leads to the esters and amides with isoxazole and isothiazole residues.

Acylation of substituted hydroxybenzaldehydes with hydrochloride of atophane acylchloride in dichloromethane in the presence of triethylamine gave esters, capable of forming (E)-azomethines when condensed with amines (4-aminoazobenzene, 4-aminoantipyrine) in methanol. In addition, an ester of atophane with a natural fragment of curcumin was obtained. Films based on (E)-azomethine with an azobenzene fragment were found to have a high polarizing ability.

In order to therapeutically destroy oncological neoplasms, chemotherapy or radiotherapy is usually applied, and in isotope medicine – short-lived radio nuclides are injected into the tumor (59Fe, 90Y, 95Zr, 99mTc, 106Ru, 114*In, 147Eu, 148Eu, 155Eu, 170Tm, 188Re, 210Po, 222Rn, 230U, 237Pu, 240Cm, 241Cm, 253Es). Binary (or neutron capture) therapy is a technology developed for the selective effect on malignant tumors using drugs that are tropic to tumors and contain non-radioactive nuclides (10B, 113Cd, 157Gd at al.). Triadic therapy involves the sequential introduction into the body of a combination of two or more separately inactive and harmless components, which are tropic to tumor tissues and capable of selectively accumulating in them or chemically interacting with each other and destroying tumor neoplasms under the action of certain sensitizing external influences. The aim of this work is quantum-chemical simulation of the electronic structure and analysis of the thermodynamic stability of new cortisone-fullerenol agents for the treatment of tumor neoplasms. The need for preliminary studies of modeling such objects is due to the very high labor intensity, cost and complexity of their practical production.

In order to therapeutically destroy neoplasms, chemotherapy or radiotherapy is usually applied, and in isotope medicine short-lived radionuclides are injected into the tumor (59Fe, 90Y, 95Zr, 99mTc, 106Ru, 114*In, 147Eu, 148Eu, 155Eu, 170Tm, 177mLu, 188Re, 210Po, 222Rn, 230U, 237Pu, 240Cm, 241Cm, 253Es). Binary (or neutron capture) therapy is a technology designed to selectively treat malignant tumors and using drugs tropic to tumors containing non-radioactive nuclides (10B, 113Cd, 157Gd at al.). Triadic therapy is the sequential introduction into the body of a combination of two or more separately inactive and harmless components, tropic to tumor tissues and capable of selectively accumulating in them or entering into chemical interaction with each other and destroying tumor neoplasms under certain sensitizing external influences. The aim of this work is to quantum-chemically simulate the electronic structure and to analyze the thermodynamic stability of new doxorubicino-fullerenol agents for the treatment of tumor neoplasms. The need for preliminary studies on the modeling of such objects is due to the extremely high labor intensity, cost and complexity of their practical production.

Tetraeicosahydroxyfullerene C60(OH)24 has a wide range of unique and useful properties that allow it to be successfully used in a number of sectors of the national economy. Interest in this compound is due to its extremely high biological potential, which manifests itself in a potentiating effect against malignant neoplasms (when used together with cisplatin) and as an agent for the delivery of radioactive isotopes in radiation medicine. This paper presents a convenient and easily scalable procedure for the synthesis and purification of C60(OH)24 tetraeicosahydroxyfullerene by catalytic bromination of C60 fullerene in liquid bromine in the presence of metallic iron. The technology of purification of the target product using ion exchange resins AB-17-8 and TOKEM-100 has been developed.