Nitrogen-containing Heterocyclic Derivatives Research Articles

Recent Developments in the Antimicrobial Potential of Some Nitrogenous Heterocycles and their SAR Studies: A Review.

Infection remains a significant global health concern, with millions of new cases and deaths occurring due to infectious diseases. Currently, chemoprophylaxis and chemotherapy are the primary treatments, but side effects and toxicities pose challenges. Pathogenic microorganisms have developed resistance to antimicrobial medications. Nitrogen containing heterocyclic scaffolds possess the potential in drug discovery and are explored in various fields like pharmaceuticals, cosmetics, and agrochemicals. To minimize antimicrobial drug resistance, there is a need to design potent, safer antimicrobial lead compounds with higher selectivity and minimal cytotoxicity. The present review aims to outline several recent developments in medicinal chemistry aspect of nitrogenous heterocyclic derivatives with the following purposes: (1) To cast light on the recent literature reports of the last eight years ranging from 2015 to 2023 describing anti-microbial potential of nitrogen-containing heterocyclic derivatives which includes pyrazole, pyrazoline, imidazole, tetrazole and quinoline; (2) To brief the recent developments in the medicinal chemistry of nitrogenous heterocyclic derivatives that is directed towards their anti-microbial profile; (3) To summarize the complete correlation of structural features of nitrogenous heterocyclic molecules with the pharmacological action including in silico as well as mechanistic studies to provide thoughts accompanying the generation of lead molecules. Antimicrobial potential of nitrogenous heterocyclic molecules has been displayed by relating the structural features of various lead candidates with their in vitro as well as in vivo antimicrobial outcomes. In contrast, in silico computational analysis from different articles also helped to predict the SAR of potent molecules. Nitrogen containing heterocycles are involved in a range of natural to synthetic analogues with keen antimicrobial potency. It is an emerging need to generate new nitrogenous heterocyclic molecules in order to tackle the drug resistance in micro-organisms with more targeted selectivity as well as specificity. To limit the side effects associated with them and to combat the microbes acquired resistance towards the current drug regimen, novel nitrogenous heterocycle based antimicrobial agents are essential to be developed. This review connects the structural units present in lead compounds with their promising antimicrobial action.

Employing a PhI(OAc)2-mediated domino reaction to assemble nitrogen-containing heterocyclic derivatives and assessing their anti-inflammatory activity.

Metal-free radical cascade synthesis of substituted pyrazole derivatives was initiated by PhI(OAc)2 at 23 °C. This protocol features wide functional group tolerance, a simple purification process without column chromatography, and an oxygen migration. Compound 5 demonstrated significant anti-inflammatory activity, indicating potential for therapy.

Design, Synthesis and Biological Activity of the 4-Thioquinoline Derivative

One of the promising areas in the creation of bioregulators is the modeling of compounds that combine several pharmacophores. The design of new highly efficient and low-toxic cytoprotectors is largely based on the derivatives of nitrogen-containing heterocycles, and quinoline plays a significant role among these compounds. The researchers evaluated the toxicity of the tested compounds in silico, in vitro, and in vivo, which allowed determiningseveral factors that affect the level of toxic action of 4-thioquinoline derivatives and the direction of non-toxic substances in this sequence. The studied 4-thioquinolines showed a moderate antiradical action in the experiment, inferior to the reference antioxidant Acetylcysteine. The most active compounds are 7-chloro-4-thioquinoline derivatives with propanoic acid residues in the 4th position. 2-(7-chloroquinolin-4-ylthio)propanoic acid and sodium salt of 2-amino-3-((7-chloroquinolin-4-yl)thio)propanoic acid showed the most promising results and their antioxidant action was higher than Tiotriazolin (the comparator) by 27 % and 41 %, respectively. The studied compounds showed a protective effect under H2O2-induced oxidative stress against male sperm according to the main indicators of sperm fertility. It was found that the compounds withresidues of succinic acid, cysteamine, or cysteine in the molecule structure are not inferior to reference drugs. On average, 2-((7-chloroquinolin-4-yl)thio)succinic acid and 2-((quinolin-4-yl)thio)ethanaminedihydrochloride exceeded the comparison drug Acetylcysteine and were on a par with the effect of Ascorbic acid.

Study of nitrogen heterocycles as DNA/HSA binder, topoisomerase inhibitors and toxicological safety

Four new nitrogen-containing heterocyclic derivatives (acridine, quinoline, indole, pyridine) were synthesized and their biological properties were evaluated. The compounds showed affinity for DNA and HSA, with CAIC and CAAC displaying higher binding constants (Kb) of 9.54 × 104 and 1.06 × 106, respectively. The fluorescence quenching assay (Ksv) revealed suppression values ranging from 0.34 to 0.64 × 103 M−1 for ethidium bromide (EB) and 0.1 to 0.34 × 103 M−1 for acridine orange (AO). Molecular docking confirmed the competition of the derivatives with intercalation probes at the same binding site. At 10 μM concentrations, the derivatives inhibited topoisomerase IIα activity. In the antiproliferative assays, the compounds demonstrated activity against MCF-7 and T47-D tumor cells and nonhemolytic profile. Regarding toxicity, no acute effects were observed in the embryos. However, some compounds caused enzymatic and cardiac changes, particularly the CAIC, which increased SOD activity and altered heart rate compared to the control. These findings suggest potential antitumor action of the derivatives and indicate that substituting the acridine core with different cores does not interfere with their interaction and topoisomerase inhibition. Further investigations are required to assess possible toxicological effects, including reactive oxygen species generation.

Synthesis and Antitumor Activity of Panaxadiol Pyrazole and Isooxazole Derivatives.

In this study, we designed and synthesized 19 nitrogen-containing heterocyclic derivatives of panaxadiol (PD). We first reported the antiproliferative activity of these compounds against four different tumor cells. The results of the MTT assay showed that the PD pyrazole derivative (compound 12b) had the best antitumor activity and could significantly inhibit the proliferation of four tested tumor cells. For A549 cells, the IC50 value was as low as 13.44±1.23 μM. Western blot analysis showed that the PD pyrazole derivative was a bifunctional regulator. On the one hand, it can down-regulate the expression of HIF-1α by acting on PI3 K/AKT signaling pathway in A549 cells. On the other hand, it can induce the decrease of CDKs protein family and E2F1 protein expression levels, thus playing a crucial role in cell cycle arrest. According to the results of molecular docking, we found that multiple hydrogen bonds were formed between the PD pyrazole derivative and two related proteins, and the docking score of the derivative was also significantly higher than that of the crude drug. In summary, the study of the PD pyrazole derivative laid a foundation for the development of ginsenoside as an antitumor agent.

Nitrogen-containing Heterocyclic Derivatives of 1,3-Thiazolidine-2,4- Diones as Dual Anti-inflammatory and Anti-oxidant Agents and their Docking Studies

Aim: The aim of this study was to carry out synthesis and characterization of nitrogencontaining heterocyclic derivatives of 1,3-thiazolidine-2,4-diones as dual anti-inflammatory and antioxidant agents and their docking studies. Background: Inflammation is a protective mechanism of our body to reduce injury and infection by microorganisms. The COX-2 enzyme is responsible for the production of prostaglandins (PG1), which are responsible for pain, fever, and a variety of other inflammatory symptoms. Reactive oxygen species (ROS) are important signalling molecules during inflammatory diseases. In an inflammatory state, polymorphonuclear neutrophils (PMNs) produce oxidative stress, which causes inter-endothelium junctions to open and the transfer of inflammatory cells over the endothelial barrier to increase. Tissue damage is caused by these inflammatory cells. Objective: The objective was to club thiazolidinediones with benzimidazole, triazole, and indole to achieve an enhanced anti-inflammatory effect. Method: In the current report, we have synthesized three new series of indole/ benzimidazole/benzotriazole clubbed with 5-arylidene-2,4-thiazolidinediones. The synthesized compounds were tested for in vivo anti-inflammatory activity using a carrageenan-induced rat paw edema model and in vitro antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing ability of plasma (FRAP) and hydrogen peroxide methods. Result: The results demonstrated that the compound PC-5 exhibited significant anti-inflammatory activity with 61.9% inhibition in comparison to the standard drug diclofenac sodium (71.4% inhibition) after 3h. The compound PC-5 exerted the highest antioxidant activity with an IC50 value of 24.68 μM amongst all synthesized compounds. Acute toxicity was also evaluated for all synthesized compounds, and the results indicated that all evaluated compounds were nontoxic in animals. The replacement of benzotriazole with benzimidazole and indole moieties diminished the anti-inflammatory activity. The hydroxysubstituted arylidene showed higher activity than methoxy, chloro substituted arylidene-2,4- thiazolididiones. Docking studies revealed that the compound PC-5 showed higher inhibition activity against the COX-2 receptor rather than COX-1. The ADME properties were also assessed that showed no violation of Lipinski’s rule and no toxicity. Conclusion: The substituents were found to exert varied activity. The docking studies revealed that the compounds showed lesser binding energy with COX-1 as compared to standard drug diclofenac. Moreover, the binding with COX-2 exhibited more binding energy, thereby proving to have specific COX2 inhibitory activity. All synthesised compounds have shown good antioxidant activity in addition to antiinflammatory activity. PC-5, PC-4, PB-5, PB-4, PA-5, and PA-4 were found to have increased antioxidant activity. Because of the presence of an electron-releasing hydroxyl group, PC-5 has proven to be a highly potent antioxidant agent.

Synthesis of N-heterocyclic amides based on (+)-camphoric acid and study of their antiviral activity and pharmacokinetics.

Efficient conditions for the synthesis of nitrogen-containing heterocyclic derivatives of (1R,3S)(+)-camphoric acid were selected. A series of heterocyclic compounds based on (+)-camphoric acid bearing pharmacophoric fragments was synthesized using the developed methodology. The compounds were tested for their antiviral activity against SARS-CoV-2 and H1N1 influenza viruses, and efficient inhibitors were identified that are of significant interest for further studies. The stability of the compounds and pharmaco-kinetics of the leader compound were studied when administered intragastrically and intramuscularly to mice at a dose of 200 mg kg-1 using the HPLC-MS/MS method.

Influence of derivatives of 2-((6-r-quinolin-4-yl)thio)acetic acid on rhizogenesis of Paulownia clones

In recent years, the demand for effective and low-toxic stimulators of rhizogenesis, which are used in microclonal propagation of plants, has been increasing in Ukraine. One of the promising directions in the search for effective compounds is molecular modeling based on known natural and synthetic compounds. The development of new highly effective and low-toxic biologically active compounds is largely based on derivatives of nitrogen-containing heterocycles, and quinoline occupies a significant place among them. Modern methods of chemometric analysis make it possible to find certain regularities in the "chemical structure – biological activity" and to select the most promising compounds for experimental research. The values of lipophilicity log P for neutral forms and the value of the distribution coefficient log D at pH = 7 were obtained by quantum chemical calculation. The values of log P and log D of the studied compounds are in the most favourable interval for overcoming the biological membranes of the cells of the root system, depending on the pH of the environment. According to Lipinski’s "rule of five", all studied compounds can show high biological activity. The toxicity of compounds of 2-((6-R-quinolin-4-yl)thio)acetic acid derivatives was evaluated by computer programs and experimentally. Among the derivatives of 2-((6-R-quinolin-4-yl)thio)acetic acid, the most toxic compounds were those that did not have alkoxy substituents in the 6th position of the quinoline ring. Sodium salts are more toxic than the corresponding acids. This is due to an increase in the bioavailability of ionized compounds. Derivatives of 2-((6-R-quinolin-4-yl)thio)acetic acid (sodium salt of 2-((quinolin-4-yl)thio)acetic acid (QAC-5) showed the greatest toxic effect on the model of the study of progressive sperm motility) and 2-((quinolin-4-yl)thio)acetic acid (QAC-1), which will reduce this indicator by 15–20% compared to intact. The toxicity assessment of the studied compounds made it possible to determine a number of factors of the structure of molecules which affect the level of toxic action of 2-((6-R-quinolin-4-yl)thio)acetic acid derivatives and the directions of creation of non-toxic growth stimulants in this series. The impact on rhizogenesis during microclonal reproduction in vitro in explants Paulownia clone 112 and further adaptation of microplants in vivo hybrid molecules of quinoline and acetic acid, which are analogues of known growth stimulants, was studied. A number of factors influencing the level of influence on rhizogenesis of the action of derivatives of 2-((6-R-quinolin-4- yl)thio)acetic acid and directions of creation of highly active substances in this series was defined. The studied compounds showed a high stimulating effect on rhizogenesis in vitro in Paulownia explants. It was established that the sodium salt of 2-((quinolin-4-yl)thio)acetic acid was the greatest stimulator of rhizogenesis compared to the corresponding original acid. The presence of alkoxy groups in the 6th position and methyl in the 2nd position of the quinoline ring of 2-((6-R-quinolin-4-yl)thio)acetic acid reduced the activity of the compounds. The selection of new effective, low-toxic, less expensive substances was carried out for further testing as potential stimulators of rhizogenesis for microclonal propagation of plants.

Design, Synthesis, and Characterization of Novel Series of Pharmacologically-important Sperm-shaped Amphiphilic Heterocyclic Compounds derived from Natural Palmitic Acid

Natural palmitic acid is a pivotal saturated fatty acid used in many biochemical processes occurring in humans and diverse living creatures, as it is the most common natural long-chain carboxylic acid whose unrivaled amphiphilic sperm-like skeleton with the inert single 15-C aliphatic chain (tail or carrier) and the very active one carboxyl group (head) represent a rich reactive entity and carrier for several organic/medicinal chemistry and pharmaceutics applications with respect to drug design and formulation. Derivatives of 1,3,4-oxadiazoles along with their 1,3,4-thiadiazoles and 1,2,4-triazoles analogs exhibit a broad spectrum of substantial pharmacological activities. Agreeing with the well-known hybridization principles and incorporation norms in hybrid chemistry, if a substituted nitrogenous heterocyclic aromatic nucleus of the three aforementioned kinds is straightway attached to the simple straight palmitic acid backbone at the position of the carboxyl group, the produced molecules are supposed to be very bioactive. This research work reports for the first once the efficient design/synthesis and characterization/elucidation of four one-tailed nitrogen-containing heterocyclic derivatives of palmitic acid constructure, which introduce a novel biologically-important pharmacophore having biocompatible amphiphilic sperm-shaped heteroaromatic structure.

Synthesis of lathyrane diterpenoid nitrogen-containing heterocyclic derivatives and evaluation of their anti-inflammatory activities

As our ongoing work on lathyrane diterpenoid derivatization, three series of lathyrane diterpenoid derivatives were designed and synthesized based combination principles, including pyrazole, thiazole and furoxan moieties. Biological evaluation indicated that compound 23d exhibited excellently inhibitory activity on LPS-induced NO production in RAW264.7 cells (IC50 = 0.38 ± 0.18 μM). The preliminary structure–activity relationships (SARs) suggested that phenylsulfonyl substituted furoxan moiety had the strongest ability to improve anti-inflammatory activity of lathyrane diterpenoids. Furthermore, compound 23d significantly reduced the level of ROS. Its molecular mechanism was related to inhibiting the transcriptional activation of Nrf2/HO-1 pathway. Based on these considerations, 23d might be a promising anti-inflammatory agent, which is noteworthy for further exploration.

SYNTHESIS AND ANTIVIRAL ACTIVITY OF N-HETEROCYCLIC HYDRAZINE DERIVATIVES OF CAMPHOR AND FENCHONE

Alkylation of the primary amino group of hydrazones of (+)-camphor and (–)-fenchone with dihaloalkanes leading to the production of novel nitrogen-containing heterocyclic derivatives was investigated. It was shown that the reaction of hydrazones with 1,2-ethanedithiol in the presence of formaldehyde with the addition of 5% Sm(NO3)3·6H2O leads to the formation of compounds containing the 1,5,3-dithiazepane fragment. The method developed by us offers the advantage of the use of commercially available reagents and good yields in the synthesis of hydrazone heterocyclic derivatives. Studies of antiviral activity have shown that camphor-based N-heterocyclic compounds can be considered promising agents with activity against influenza A.

Design, in silico Analysis, Synthesis and Evaluation of Novel Benzofused Nitrogen Containing Heterocyclic N-Substituted Mercaptobenzimidazole Derivatives as Potential Antimicrobial Agent

Benzimidazole containing mercapto group at the 2nd position is attractive nucleus for the modification with wider pharmacological activities. The aim of this study is to design benzofused nitrogen containing heterocyclic derivatives of mercapto benzimidazole using molecular docking. Using an effective procedure, N-substituted mercapto benzimidazole derivatives was synthesized. The antimicrobial activity of all the synthesized compounds was tested against four different organisms viz. E. coli, Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans. Molecular docking of mercapto benzimidazole derivatives against DNA gyrase subunit B PDB: 5l3j and Staphylococcus aureus tyrosyltRNA synthetase PDB:1jij was performed using docking protocol. The compound binds to the active site of DNA gyrase subunit B (1KZN) in a docking study, indicating that it may have antimicrobial activity. Compounds MB3 and MB5 have good antimicrobial capacity whereas compound MB4 has the high activity against Candida albicans.

Triflumizole as a Novel Lead Compound for Strigolactone Biosynthesis Inhibitor

Strigolactones (SLs) are carotenoid-derived plant hormones involved in the development of various plants. SLs also stimulate seed germination of the root parasitic plants, Striga spp. and Orobanche spp., which reduce crop yield. Therefore, regulating SL biosynthesis may lessen the damage of root parasitic plants. Biosynthetic inhibitors effectively control biological processes by targeted regulation of biologically active compounds. In addition, biosynthetic inhibitors regulate endogenous levels in developmental stage- and tissue-specific manners. To date, although some chemicals have been found as SL biosynthesis inhibitor, these are derived from only three lead chemicals. In this study, to find a novel lead chemical for SL biosynthesis inhibitor, 27 nitrogen-containing heterocyclic derivatives were screened for inhibition of SL biosynthesis. Triflumizole most effectively reduced the levels of rice SL, 4-deoxyorobanchol (4DO), in root exudates. In addition, triflumizole inhibited endogenous 4DO biosynthesis in rice roots by inhibiting the enzymatic activity of Os900, a rice enzyme that converts the SL intermediate carlactone to 4DO. A Striga germination assay revealed that triflumizole-treated rice displayed a reduced level of germination stimulation for Striga. These results identify triflumizole as a novel lead compound for inhibition of SL biosynthesis.

Novel amphiphilic dextran esters with antimicrobial activity

New amphiphilic dextran esters were obtained by polysaccharide functionalization with different substituted 1,2,3-triazoles-4-carboxylic acid via in situ activation with N, N′-carbonyldiimidazole. Nitrogen-containing heterocyclic derivatives were achieved by copper(I)-catalyzed cycloaddition reaction between organic azides and ethyl propiolate. Structural characteristics of the compounds were studied by elemental analysis, Fourier transform infrared and nuclear magnetic resonance spectroscopy (1H and 13C‐NMR). Thermogravimetric analysis, differential scanning calorimetry and wide-angle X-ray diffraction were used for esters characterization. Properties of polymeric self-associates, formed in aqueous solution, were studied by dynamic light scattering and transmission electron microscopy. The critical aggregation concentration values for dextran esters, determined by fluorescence spectroscopy, were in the range of 4.1-9.5 mg/dL. Antimicrobial activity, investigated for some of the polymers by disc-diffusion method, pointed out that polysaccharide esters were active.

Study of the spectra of asymmetric triazines with growth-stimulating activity

Derivatives of nitrogen-containing heterocycles, in particular compounds of symmetric and asymmetric triazines, are widely used in agriculture as regulators of plant growth and development. Among the derivatives, the most well-known use of symmetric derivatives, however, they are difficult to biodegrade and accumulate in the soil, and as a result in the plants themselves. Therefore, asymmetric triazines, which are easily decomposed in the environment, are more promising in practical terms. Currently, it is very important to use environmentally friendly plant growth and development regulators that do not contain impurities, so much attention is paid to the identification of synthesized compounds of asymmetric triazines with a substituent in position 5 using UV, IR and Mass spectroscopy.

The effect of the structure of derivatives of nitrogen-containing heterocycles on their anti-influenza activity

An adequate QSAR model based on the simplex representation of the molecular structure was built in order to optimize the search for new anti-influenza agents. Structural interpretation of the model allowed us to identify molecular fragments that determine the activity of compounds against human influenza viruses. Further virtual screening and targeted synthesis allowed us to select a group of potentially effective compounds, three of which, derivatives of piperidine and isoindoline, turned out to be the most promising.

Copolymers of sodium 4-styrene sulphonate and vinyl derivatives of nitrogen-containing heterocycles

The formation of ion-exchange composite materials based on high molecular weight precursors appears to be an intensively developing area in the synthesis of proton-conducting membranes for fuel cells. In such membranes, proton transfer is often provided by functional polymers simultaneously containing sulphonic acid groups in their composition units along with fragments of vinyl derivatives of nitrogen-containing heterocyclic bases. Proton exchange activity in the latter is determined by the possibility of doping with inorganic acids. In the framework of this study, for the further formation of hybrid composite membranes under conditions of radical initiation, copolymers of sodium 4-styrene sulphonate (SSt) with 4-vinylpyridine (VP) and 1-vinylimidazole (VIM) were obtained. The monomodal nature of the turbidimetric titration curves for solutions of copolymerisation reaction products indicates the presence of true copolymers during the process of formation. The composition and structure of the copolymers were characterised using data from elemental analysis, as well as from IR and 13 C NMR spectroscopy. Constants of the relative activity for the monomers and the microstructure parameters of the polymer chains are calculated according to the non-linear leastsquares method using the MathCAD package. The calculated copolymerisation constant values indicate a greater reactivity of SSt in comparison with nitrogen-containing monomers. The lengths of the monomer unit blocks depend on the composition of the initial mixture and vary over a wide range from 1 to 18. The possibility of varying the length of the unit blocks in the composition of the copolymers will affect the ion-conducting properties of hybrid composites formed on their basis. The stability of the copolymers to thermal oxidative degradation by heating in air was studied using the differential scanning calorimetry (DSC) method. The copolymers demonstrated significant thermo-oxidative stability. Decomposition temperatures were 350 °С and 400 °С for SSt-VIM and SSt-VP copolymers, respectively.

Nitrogen-Containing Heterocyclic Derivatives of Maleopimaric Acid by Carboxyl Function and their Antioxidant Activity

New N-heterocyclic maleopimaric acid derivatives were prepared and shown to affect free-radical oxidation in model systems, in particular, to suppress reactive oxygen species generation and stimulated lipid peroxidation in model systems containing lipoproteins.

Facile One-Pot Synthesis Methodology for Nitrogen-Containing Heterocyclic Derivatives of 3,5-Disubstituted 4,5-Dihydro-1H-Pyrazole, Their Biological Evaluation and Molecular Docking Studies

A series of 2-pyrazoline derivatives (PS-1 to PS-16) were synthesized by reacting different aromatic/heteroaromatic aldehydes and ketones, in a two-step reaction through Claisen – Schmidt condensation, followed by cyclization of the resulting chalcones with hydrazine hydrate in the presence of a base using conventional and microwave approaches. The synthesized derivatives were characterized by various physicochemical methods including IR, 1H-NMR, 13C-NMR, and mass spectroscopic data and elemental analysis. The antidepressant and anti-anxiety activities were evaluated using suitable animal models. Compounds PS-3, and PS-14 showed noticeable antidepressant activity, by reducing the duration of immobility in both tests, while compounds PS-9 and PS-12 were found to possess good anxiolytic activity (by increasing the number of arm entries and open arm exploratory time) at the tested doses (50 and 100 mg/kg b.w.) in comparison to standard drugs imipramine and diazepam, respectively. In order to elucidate binding interactions of the synthesized derivatives to the MAO-A target protein, molecular docking was employed which demonstrated the key interactions with amino acid residues Phe208, Asn181, and Tyr407 at the binding site. Further, the ADME properties of the synthesized derivatives were predicted and found to fall within the stated limits.

Hemostatical activity of new benzylammonium salt, 2-[3-methyl-1-npropyl-7-(1,1-dioxotiethanyl-3)xantinyl-8-thio]acetic acid

Background: Preventing and control of bleeding is important in various areas of clinical medicine in the light of increasing number of patients with hemorrhagic manifestations, extensive use of anticoagulants, increasing number of invasive diagnostic, and treatment methods. However, the drugs traditionally used in medical practice to control bleeding are often inefficient and unable to lead to effective reduction in blood loss. One of the ways to find new methods of bleeding prophylaxis is to develop means of pharmacological correction of hemostasis system. The results of the previous research show potentially high activity of some new nitrogen-containing heterocyclic derivatives relating to hemostasis system in vitro and in vivo. Aims and Objectives: To examine system hemostatic activity of first synthesized benzylammonium salt 2-[3-methyl-1-npropyl-7-(1,1-dioxothietanil-3) xantinyl-8-thio]acetic acid (Compound I) under experimental conditions in vitro and in vivo. Materials and Methods: Experimental work in vitro is performed on the blood of healthy male donors, under conditions in vivo it is done on intraperitoneal injection of equimolar concentrations of the test substances. Thromboelastography (TEG) was carried out with apparatus TEG 5000. The analysis of the thromboelastograms enabled to define general tendency of coagulation, functional activity of platelets and fibrinogen, fibrinolysis activity, and physicomechanical properties of the formed clots. The influence of firstly synthesized xanthine derivative and ethamsylate on the functional activity of platelets in vitro and in vivo was studied using a laser platelet aggregation analyzer ”Biola 230LA.” The research evaluated the general nature of aggregation, value of maximum aggregation, maximum rate of aggregation, and average size of platelet aggregates. Experimental evaluation of the system specific hemostatic activity in vivo was carried out using the model of parenchymatous bleeding in immature male rats. Results: The interference came amid registration of bleeding stop time and extent of blood loss. Proagregate effect of Compound I is successfully realized into the system hemostatic activity under conditions of parenchymatous bleeding, exceeding the performance of the control group and the etamsylate group. Conclusion: The findings reveal potentially high systemic hemostatic activity of Compound I, convincing of the need to further study this compound and its analogues to create on their basis highly efficient, selective correctors of hemostasis system.