Nowadays, the prevalence of metabolic syndrome (MS) is a serious problem among the world’s population. Metabolic syndrome includes the so-called “deadly” quartet – hypertension, type 2 diabetes mellitus (diabetes mellitus), dyslipidemia and alimentary obesity. After all, type 2 diabetes is included in the list of pathologies of the metabolic syndrome, it is important to find ways to alleviate the disease. Derivatives of such a heterocyclic system as xanthine are of great interest in this aspect. The aim of the study was to explore the hypoglycemic activity of newly synthesized water-soluble derivatives of 3-benzyl-8-substituted xanthines. Materials and methods. We obtained water-soluble potassium 3-benzyl-8-R-xanthin-7-ides, the structure and individuality of which were confirmed by a set of physical-chemical studies. Results. The hypoglycemic effect of the newly synthesized compounds was assessed by an oral glucose tolerance test. The obtained data were processed using modern statistical in silico-methods. Conclusions. The results of the hypoglycemic activity study among the potassium salts of 3-benzyl-8-substituted xanthine derivatives showed, that some new compounds are in close vicinity to the reference drug’s hypoglycemic action.

One of the most important tasks of our indigenous pharmaceutical science is the necessity for new medicines because existing drugs are characterized by various side effects, resistance, high toxicity, and so on. New bioactive molecule synthesis utilizes substances of natural origin as well as chemically modified ones. Thus, the researcher’s attention is mainly focused on 3-,7-,8-substituted derivatives of the natural heterocyclic xanthine system, which possess a wide range of pharmacological action. Synthesis of a novel of (3-benzyl-8-propylxanthin-7-yl)acetohydrazides with antimicrobial and diuretic activities described in the paper. The aim of this work is to develop efficient methods for synthesis of (3-benzyl-8-propylxanthin-7-yl)acetohydrazide derivatives, and to study their physical-chemical properties. Materials and methods. Two-hour boiling of propyl 2-(3-benzyl-8-propylxanthine-7-yl)acetate by excess hydrazine hydrate in propan-2-ol medium have yielded the key the key intermediate 2-(3-benzyl-8-propylxanthine-7-yl)acetohydrazide. Further transformation of the latter has led to formation of corresponding acetohydrazide derivatives achieved by the reaction with aliphatic, aromatic, heterocyclic aldehydes, and ketones. The structure and the relative configuration of the synthesized compounds were elucidated by analyzing their physical-chemical data. Results. The synthesis and optimization of reaction conditions of (3-benzyl-8-propylxanthin-7-yl)acetohydrazide derivatives were conducted. The identification of all synthesized compounds was aided by various physical-chemical methods (thin layer chromatography, elemental analysis, IR, and 1H NMR spectroscopy). Conclusions. As a result of synthetic research the preparative synthesis method of (3-benzyl-8-propylxanthin-7-yl)acetohydrazide derivatives possessing antimicrobic, and diuretic activities was developed.

The dynamics of luminescence indices of blood leukocytes, fluorochromated with acridine orange, were studied in operated patients. The most informative of them was the luminescence intensity at 640 nm to characterize the state of immunity. It radically increased during the traumatic periods of the operation and during the activation of reparative processes. Significant radical changes of I = 640 nm in blood lymphocytes, which occurred during the traumatic period of the operation, persisted for a week after the operation, indicating the degree of participation of the immune system in reparative regeneration.

Over the last few decades, there was significant interest in applying various xanthine derivatives to treat several diseases as highly potent antioxidant agents. Our study introduced several pharmacophore groups in the xanthine core to improve its antioxidant activity and increase biological fluids' solubility. We synthesized a set of new low-toxic 3-methylxanthine derivatives. Such compounds bear challenging scaffolds for finding effective antioxidant agents with broad application in medicine and pharmacy.

The current stage of scientific and technological progress in pharmaceutical science is associated with the development of the targeted synthesis of biologically active compounds and the creation of new highly effective and low-toxic drugs on their basis that could compete with expensive imported drugs. A wide range of biological activity of natural xanthines stimulated the search for biologically active compounds among their synthetic analogs, which led to the creation of a row of drugs (Aminophylline, Diprophyllinum, Pentoxiphyllinum, Complamin, etc.) that are used successfully to nowadays. It is known that derivatives of 1- and 7-benzylxanthines exhibit versatile pharmacological effects. It should be noted that 8-bromoxanthines containing benzyl substituents at positions 1 or 7 are convenient synthons for further structural modification of the xanthine molecule. The aim of this work is to study the reaction conditions of 8-bromo-7-m-bromobenzyl-3-methylxanthine with primary and secondary aliphatic amines and to study their physical-chemical properties. Materials and methods . The melting point has been determined with the open capillary method using the PTP-M device. Elemental analysis has been performed with the Elementar Vario L cube, NMR-spectra has been taken on a spectrometer Bruker SF-400 (operating frequency – 400 MHz, solvent – DMSO, internal standard – TMS). Results. The reaction of 7-m-bromobenzyl-8-bromo-3-methylxanthine with amines was carried out in a steel autoclave in methanol at 170 °C. It should be noted that despite the excess of the primary or secondary amine, only the Bromine atom in position 8 of the xanthine molecule was replaced with the formation corresponding 8-amino-7-m-bromobenzyl-3-methylxanthines. The obtained 8-aminoxanthines were white crystalline compounds with high melting points in virtue of their existence in the form of associates due to hydrogen bonds. The structure of the synthesized compounds was unambiguously proved by the method of NMR-spectroscopy. Conclusions. Simply implemented methods for the synthesis of 8-amino-7-m-bromobenzyl-3-methylxanthines were developed. NMR-spectroscopic study of the obtained compounds, which clearly confirms their structure, was conducted. The prospective of the synthesized compounds for subsequent modification of their structure was demonstrated.

Modern antibiotics and synthetic antimicrobial agents play a leading role in the treatment of bacterial infections. Despite their effectiveness, they cause a number of side effects, and thus the search for new antimicrobial and antifungal agents is currently one of the problems of pharmaceutical science of current interest. Literary data suggest that xanthine derivatives exhibit activity in relation to some strains of pathogenic microorganisms and fungi.

Modern antibiotics and synthetic antimicrobial agents play a leading role in the treatment of bacterial infections. Despite their effectiveness, they cause a number of side effects, and thus the search for new antimicrobial and antifungal agents is currently one of the problems of pharmaceutical science of current interest. Literary data suggest that xanthine derivatives exhibit activity in relation to some strains of pathogenic microorganisms and fungi. The aim of this work is to develop a method for the synthesis of new derivatives of xanthine-8-aminoalkanoic acids and to study their physical and chemical properties, as well as their antimicrobial and antifungal effects. Materials and methods. The melting point has been determined with the help of an open capillary method with PTP-M device. Elemental analysis has been performed with the help of the instrument Elementar Vario L cube, NMR-spectra have been taken on a spectrometer Bruker SF-400 (operating frequency of 400 MHz, solvent DMSO, internal standard – TMS). Study of antimicrobial and antifungal activity of synthesized compounds has been performed by a two-fold serial dilution method. Standard test strains have been used for the study: Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923, Pseudomonas aeruginosa ATCC 27853, Candida albicans ATCC 885-653. Dimethylsulfoxide was used as the solvent of the compounds. Results. The reaction of 8-brom-7-ethylxanthines with an excess of the corresponding aminoalkanoic acid in an aqueous DMF medium in the presence of an equimolar (in relation to the amino acid) amount of baking soda leads to the formation of the corresponding 7-ethylxanthinyl-8-aminoalkanoic acids. Structure of synthesized compounds was definitely proved by 1Н NMR-spectroscopy. Conducting primary screening research of antimicrobial activity of 7-ethylxanthinyl-8-aminoalkanoic acids derivatives, which revealed moderate and weak activity in concentrations 50–100 mcg/ml. Conclusions. A preparative method of synthesis of not described in the literature 7-ethylxanthinyl-8-aminoalkanoic acids is developed. The structure of the synthesized compounds has been proved with the help of data of the 1H NMR spectroscopy. The antimicrobial and antifungal effects of the obtained compounds have been studied. The perspective of xanthine-8-alkanoic acids for the further search of biologically active compounds is shown.

According to the International Diabetes Federation in 2015 were registered 59.8 million patients with diabetes in Europe. Synthetic drugs are widely applied in addition to a variety of insulins to normalize blood glucose level. It should be noted that the oral anti-diabetic drugs are the common therapeutic agents for the treatment of diabetes mellitus type II, and therefore the search for new non-toxic hypoglycemic agents is one of the most urgent problems of modern pharmaceutical science. It is known that 7,8-disubstituted xanthine derivatives exhibit hypoglycemic activity. The aim of this work lies in developing unique method to synthesize undocumented in other scientific papers 7-n-butyl-3-methyl-8-thioxanthine derivatives and also studying of their hypoglycemic activity. Acute toxicity of synthesized compounds has been studied with the application of Prozorovsky’s method. The glucose homeostasis characteristic has been performed on carbohydrate tolerance that has been determined by the glucose load test on the control group and on the intact rats. The reactions of 7-n-butyl-3-methyl-8-thioxanthine with benzylchlorides, bromoketones, esters and an amide of chloroacetic acid have been studied. Reactions of mentioned syntons proceed smoothly in aqueous propanol-2 environment and lead to the formation of the corresponding 8-benzyl-, benzoylmethylthioxanthines and xanthinyl-8-thioacetic acid derivatives. Accessible laboratory method has been elaborated to synthesize unspecified in scientific papers earlier 8-thiosubstituted 7-n-butyl-3-methylxanthine by reacting 7-n-butyl-3-methyl-8-thioxanthine with benzylchlorides, bromoketones, esters and an amide of chloroacetic acid, their structure having been proved by NMR-spectroscopy data. The acute toxicity of synthesized compounds has been studied. It has been established that LD50 is in the range 820–2477 mg/kg, i. e. obtained substances are low-toxic and practically non-toxic according to Sidorov’s classification. Also the study of hypoglycemic activity of synthesized compounds has been carried out. A significant perspective for further research to find the original antidiabetic agents has been shown by bioassay results. It has been found that 7-n-butyl-3-methylxanthinyl-8-thioacetamide is more active than reference substances.

A wide range of biological activity of natural xanthines stimulated the search of biologically active compounds among their synthetic analogues, which led to the creation of a number of medicines (Nihexynum, Proxyphyllinum, Protheobrominum, etc.), which have been successfully applied till present time. It should be noted that the search of new biologically active compounds among xanthine derivatives does not stop. Previously, we had found that xanthine thioderivatives exhibits antioxidant, diuretic, hypoglycemic, antitumor, antimicrobial, anti-inflammatory, analgesic activity. The aim of the work is to elaborate simple laboratory methods of 7-ethyl-3-methylxanthine derivatives synthesis, unspecified in scientific papers earlier, – the basis for the creation of original antimicrobial and antifungal medicines. Materials and methods of research. The melting point has been determined with the help of an open capillary method with PTP-M device. Elemental analysis has been performed with the help of the instrument Elementar Vario L cube, NMR-spectra have been taken on a spectrometer Bruker SF-400 (operating frequency of 400 MHz, solvent DMSO, internal standard – TMS). Study of antimicrobial and antifungal activity of synthesized compounds has been performed by a two-fold serial dilution method. Standard test strains have been used for the study: Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923, Pseudomonas aeruginosa ATCC 27853, Candida albicans ATCC 885-653. Dimethylsulfoxide was used as the solvent of the compounds. Results and their discussion. Under short-time heating up of 7-ethyl-3-methyl-8-thioxanthine with methyl chloroacetate in a water-ethanol solution of sodium hydroxide leads to the formation of the corresponding ester. 3-Methyl-7-ethylxanthinyl-8-thioacethydrazide was obtained by hydrazinolysis of methyl(3-methyl-7-ethylxanthinyl-8-)thioacetate. Corresponding 7-ethyl-3-methylxanthinyl-8-thioacetic acid benzylidene hydrazides were obtained by the reaction of hydrazide with aromatic aldehydes. Structure of synthesized compounds was definitely proved by NMR-spectroscopy. Conducting primary screening research of antimicrobial activity of 8-thioderivatives of 7-ethyl-3-methylxanthine, which revealed moderate and weak activity in concentrations 50–100 mcg/ml. 2-Methoxy-5-bromobenzylidenehydrazide showed a pronounced antifungal effect. Conclusions. The preparative method of synthesis of 7-ethyl-3-methylxanthinyl-8-thioacetic acid benzylidene hydrazides, unspecified in scientific papers earlier, was developed. The structure of the synthesized compounds and their existence in the form of a mixture of E- and Z-isomers in the ratio 2:1 was proved with the help of the NMR spectroscopy data. The antimicrobial and antifungal effects of the obtained compounds were studied. Priorities for further research of biologically active compounds have been outlined.

Introduction. Heterocyclic compounds play an important role in the metabolic processes of human organism. Structures of vitamins, nucleotides, chromoproteins are based on Nitrogen-containing heterocycles (purine, pyrimidine, thiazole etc). Thus, it was obvious to use these organic substances as basic molecules for synthetic research of biologically active compounds which could be used for treatment of different pathological processes. In their research, some scientist pay special attention to xanthine derivatives that are well-known low toxic natural compounds with wide spectrum of pronounced pharmacological properties (antioxidant, diuretic, antibacterial, anti-inflammatory etc). Insertion of carboxyl group in the structure of xanthine molecule is a prospective ability of its synthetic potential increasing. Aim of our research was the development of method of 3-benzyl-8-propylxanthinyl-7-acetic acid and its derivatives synthesis and studying their physical-chemical properties. Materials and methods. Melting points were determined using capillary method on DMP (M). 1Н NMR-spectra were recorded by Varian Mercury VX-200 device (company «Varian», USA) solvent – (DMSO-d6), internal standard – ТМS. Elemental analysis of obtained compounds was produced on device Elementar Vario L cube. Results and discussion. We selected 3-benzyl-8-propyl xanthine as initial compound for our study. By its interaction with chloroacetic acid, chloroacetamide or propyl chloroacetate in DMF in the presence of calculated amount of NaHCO3 we synthesized 3-benzyl-8-propylxanthinyl-7-acetic acid its ester and amide. At the same time we found that obtaining of xanthinyl-7-acetic acid by hydrolysis of its ester produced with higher yield. On the next stage of our research we synthesized a number of water-soluble salts of 3-benzyl-8-propylxanthinyl-7-acetic acid by reaction of acid with different primary and secondary amines. The structures of all obtained compounds were proved by the elemental analysis and 1H NMR-spectroscopy. Conclusions. Obtained results of our work can be used for further search of biologically active compounds among xanthine derivatives with carboxyl residue.

It has been found that natural xanthines, as well as their synthetic analogs, possess the diuretic effect. Analysis of the literature proves that there is a great opportunity of applying synthetic derivatives of N-methylated xanthines as potential diuretics.Aim. To develop preparative methods of the synthesis of 8-aminosubstituted of 7-(2-hydroxy-3-p-metoxyphenoxypropyl-1)-3-methylxanthine and study their physical, chemical and biological properties. Results. The synthesis of a series of 8-aminosubstituted of 7-(2-hydroxy-3-p-metoxyphenoxypropyl-1)-3-methylxanthine was carried out. According to the results of the biological testing the compounds synthesized belong to the toxicity of class IV. 7-(2-Hydroxy-3-p-methoxyphenoxypropyl-1)-8-(furyl-2-methylamino)-3-methylxanthine xanthine shows the highest diuretic activity, and hence, requires a more in-depth study since it is twice more active than hydrochlorothiazide. It should be emphasized that all compounds synthesized exhibit a marked diuretic effect. Experimental part. 8-Bromo-7-(2-hydroxy-3-p-methoxyphenoxypropyl-1)-3-methylxanthine was obtained by heating 8-bromo-3-methylxanthine with p-methoxyphenoxymethyloxirane in butanol-1 and in the presence of N,N-dimethylbenzylamine. 8-Aminosubstitutied of 7-(2-hydroxy-3-p-metoxyphenoxypropyl-1)-3-methylxanthine was obtained by boiling of bromoalcohol with the primary and secondary amines. The structure of the compounds synthesized was unambiguously confirmed by NMR-spectroscopy. The acute toxicity of the compounds obtained was studied by Kerber method. The study of the diuretic activity of the compounds was carried out using Ye. Berkhin method. Hydrochlorothiazide was used as a reference substance. Conclusions. Simple methods for the synthesis of 8-amino-7- (2-hydroxy-3-p-methoxyphenoxypropyl-1)-3-methylxanthines have been developed. The structure of the compounds synthesized has been confirmed by the method of NMR 1H-spectroscopy. The acute toxicity and the diuretic activity of the compounds obtained have been studied.

It is known that 8-aminosubstituted N-methylated xanthines are dipeptidyl peptidase-4 antagonists, ligands for 5-hydroxytryptamine receptors and exert diverse biological effects. Previously, it was found that the 7-alkyl-8-piperazinoxanthines exhibit diuretic, depremic, analgesic effect. Some amino derivatives of 7-metilxanthine are promising antioxidants and 8-amino-7-ethyl-3-methylxanthine detects a distinct hypoglycemic effect. The aim of this work is to provide new derivatives of 7-methylxanthine – promising bioactive compounds and to study their physical and chemical properties as a basis for further structural modification of the molecule. Materials and methods. The melting point has been determined with the help of an open capillary method with PTP-M device. Elemental analysis has been performed with the help of the instrument Elementar Vario L cube, NMR-spectra have been taken on a spectrometer Bruker SF-400 (operating frequency of 400 MHz, solvent DMSO, internal standard – TMS). Results. It is established that the heating the source of bromxantine with an excess of primary amines in a mixture of water and dioxane leads to the formation of the corresponding 8-aminosubstituted 7-ethyl-3-methylxanthine. The reaction of 8-bromo-7-ethyl-3-methylxanthine and 8-bromo-7-ethyltheophylline with the more nucleophilic N-substituted piperazine is performed in the same conditions, but requires much less time and is accompanied by the formation of the corresponding 8-N-piperazinxanthines. Taking into account the amphoteric properties of imidazole it was possible to obtain 7-ethyl-8-(midazol-1)-3-methylxanthine through the reaction in dimethylformamide in the presence of equimolar amount of NaHCO3. 8-(4-Tret- butoxycarbonylaminopiperidinyl-1)-7-ethyl-3-methylxanthine and 8-(4-tret-butoxycarbonylamino-1)-7-ethyltheophylline are obtained by heating equimolar amounts of original bromxanthines, 4-tret-butoxycarbonylaminopiperidine and NaHCO3. The structure of the synthesized compounds is unambiguously proved by the method of NMR spectroscopy. The synthesized compounds are white crystalline substances soluble in hot alcohols, dioxane, DMF. The fact that 8-N,N-diethylamino-7-ethyl-3-methylxanthine and 7-ethyl-8-(midazol-1)-3-methylxanthine are well soluble in diluted acid solutions, can be used to obtain new bioactive salts with organic and inorganic acids. The presence of free N1H group enables the synthesis of new 1,3,7,8-tetrasubstituted of xanthine by the introduction of a variety of electrophilic reagents into the position of 1 uracil part of the molecule. Conclusions. Simply implemented methods for the synthesis of 8-amino-7-methylxanthine are developed. NMR-spectroscopic study of the obtained compounds, which clearly confirms their structure, is conducted. The prospective of the synthesized compounds for subsequent modification of their structure is demonstrated.

The aim of the research was to study the basic descriptors of frontier molecular orbitals of 3- aryl (aralkyl) xanthine using semi-empirical quantum- chemical methods and substantiate their impact on the manifestation of anti-radical activity.Comparison of received data and calculated descriptors values revealed linear dependence of anti-radical activity on the highest occupied and lowest unoccupied molecular orbitals energy values.

Aim. Selection of basic compounds is a key moment of the novel drug substances development process. Nowadays, it is possible to model the properties of biologically active substances with the help of computer technologies and the special software. We selected 3-benzyl-8-propylxanthine as a promising basic compound with a large variability of further chemical modification by insertion of well-known pharmacophores. Our decision was based on in silico-calculations. Materials and methods. This compound has been synthesized by condensation of 1-benzyl-5,6-diaminopyrimidine-2,4-dione with butanic acid. Then we obtained a number of water-soluble 3-benzyl-8-propylxanthinides-7 on the basis of initial substance. Synthesis has been made by reaction of 3-benzyl-8-propylxanthine with inorganic or organic bases in an aqueous or aqueous-alcoholic solution. Conclusion. The structure of synthesized compounds has been proved using elemental analysis and 1H NMR-spectroscopy.

Aim. Selection of basic compounds is a key moment of the novel drug substances development process. Nowadays, it is possible to model the properties of biologically active substances with the help of computer technologies and the special software. We selected 3-benzyl-8-propylxanthine as a promising basic compound with a large variability of further chemical modification by insertion of well-known pharmacophores. Our decision was based on in silico -calculations. Materials and methods. This compound has been synthesized by condensation of 1-benzyl-5,6-diaminopyrimidine-2,4-dione with butanic acid. Then we obtained a number of water-soluble 3-benzyl-8-propylxanthinides-7 on the basis of initial substance. Synthesis has been made by reaction of 3-benzyl-8-propylxanthine with inorganic or organic bases in an aqueous or aqueous-alcoholic solution. Conclusion. The structure of synthesized compounds has been proved using elemental analysis and 1 H NMR-spectroscopy.

The aim of the research was to study the basic descriptors of frontier molecular orbitals of 3- aryl (aralkyl) xanthine using semi-empirical quantum- chemical methods and substantiate their impact on the manifestation of anti-radical activity. Comparison of received data and calculated descriptors values revealed linear dependence of anti-radical activity on the highest occupied and lowest unoccupied molecular orbitals energy values.

Introduction. Analysis of last years’ literature shows, that the most wide spread drugs are those, which contain in their structures heterocyclic fragment. Such trend could be explained by the fact that, heterocycle containing compounds are the part of the number of substances, which play an important role in the metabolic processes. It should be noted, that most of these drugs have unpleasant side effects and some of them are rather toxic. Xanthine derivatives are low toxic natural compounds with wide spectrum of pronounced pharmacological properties (antioxidant, diuretic, antibacterial, anti-inflammatory etc.) and high variability of chemical modification, that make these compounds handy objects for pharmaceutical research. Thus, synthesis of novel less toxic biologically active compounds – potential medicines – by chemical modification of well-known natural substances, is one of the most important tasks of modern pharmaceutical science. Aim of our research was the development of method of 3-aryl(aralkyl)-8-hydrazinemethylxanthines and their N-substituted derivatives synthesis and studying their physical-chemical properties. Materials and methods. Melting points were determined using capillary method on DMP (M). 1Н NMR-spectra were recorded by Varian Mercury VX-200 device (company «Varian» – USA) solvent – (DMSO-d6), internal standard – ТМS. Elemental analysis of obtained compounds was produced on device Elementar Vario L cube. Results and discussion. We selected 3-aryl(aralkyl)-8-chloromethylxanthines as initial compounds for our study. By their interaction with hydrazine hydrate we obtained respective 8-hydrazinemethylxanthines. The next stage of our research was further chemical modification of obtained 8-hydrazinemethylxanthines using the high ability of hydrazine residue for nucleophilic addition reactions. So, we studied the interaction of 3-aryl(aralkyl)-8-hydrazinemethylxanthines with phenylisothiocyanate and carbonyl compounds and synthesized number of N-substituted 8-hydrazinemethylxanthines. The structures of all obtained compounds were proved by the elemental analysis and 1H NMR-spectroscopy. Conclusions. Obtained results of our work can be used for further search of biological active compounds among xanthine derivatives with hydrazine residue.

У статті наведено результати дослідження енерготропної дії потенційних нейропротекторних сполук - похідних ксантину С -3 та С -4 порівняно з референс - препаратом мексидолом на моделі ішемічного інсульту , яку відтворювали шляхом двобічного перев ' язування загальних сонних артерій .

Diabetes mellitus is a chronic endocrine disease. It etiology is the impact of both endogenous (genetic) and exogenous factors that cause absolute or relative shortage of insulin or not effective use of it, which in turn leads to disruption of all kinds of substances exchange. The study of this problem is actual due to the high prevalence of diabetes, chronic disease, the tendency to increase the number of patients, their high morbidity and mortality. Diabetes is characterized by high blood glucose levels, which eventually leads to various complications associated with many human systems damage. Hormones (insulin and its analogues) and synthetic drugs (sulfonylureas, biguanides etc.) are used For the treatment of diabetes, but their high toxicity, cumulativeness, various side effects (autoimmunization, cutaneous allergic reactions, disturbance of the micro flora of the digestive tract), and the formation of insulin resistance restrict the use of these drugs in clinical practice. On this aspect the attention of researchers is attracted to xanthine derivatives, which are known as substances with wide range of biological activities including hypoglycemic.Based on the above, the search and development of new drugs among new 3-R-substituted xanthine, which would have hypoglycemic effect and would be deprived of most side effects is an acute problem of modern medical and pharmaceutical sciences.The aim of this study was to investigate the hypoglycemic activity of newly synthesized derivatives of 3-benzyl-8-methylxanthine and establish certain patterns "structure-activity" relationship.Materials and methodsAs objects of study for hypoglycemic activity we used derivatives of 3-benzyl-8-methylxanthine synthesized at the Department of Biochemistry and LaboratoryDiagnostics ofZaporizhzhyaStateMedicalUniversity.Hypoglycemic action of xanthine derivatives evaluated by intraperitoneal glucose tolerance test, which was reproduced by injection to animals (white rats weighing 160-230 g) glucose at a dose of 2 g/kg. The experimental animals were divided in 14 groups of 7 animals in each:1. Intact – animals administered saline;2. Control – modeling hyperglycemia without treatment.3-13. Animals were injected xanthine derivatives at the background of hyperglycemia modeling.14. The animals were injected metformin at the background of hyperglycemia modeling.We determined glucose level in blood using a glucometer «Accu Chek Active» after 30 and 60 minutes.Research results processed by modern methods of analysis using Student t-test. We used the level of statistical significance of differences of research results - p<0.05.Results and their discussion Presence of methyl and benzyl group or acetate residue at position 7 of xanthine bicycle resulted in incresing of glycemia in the blood of experimental animals. Replacing carboxyl hydroxyl to propoxy group or adding naphtylmethyl substituent reduced glycemia (compound 8 and compound 3) after 30 min glucose injection.ConclusionsAs a result of the research it was found that most hypoglycemic activity among the compounds that were studied, has 3-benzyl-7-(2-naphtylmethyl)-8-metylxanthine. Obtained results can be used in further searching of potential biologically active substances with hypoglycemic properties among derivatives of 3-benzylxanhine.