Nitrogen Heterocycles Research Articles

Crystal structures and photophysical properties of mono- and dinuclear ZnII complexes flanked by triethylammonium

Two new zinc(II) complexes, triethylammonium dichlorido[2-(4-nitrophenyl)-4-phenylquinolin-8-olato]zinc(II), (C6H16N){Zn(C21H13N2O3)Cl2] (ZnOQ), and bis(triethylammonium) {2,2′-[1,4-phenylenebis(nitrilomethylidyne)]diphenolato}bis[dichloridozinc(II)], (C6H16N)2[Zn2(C20H14N2O2)Cl4] (ZnBS), were synthesized and their structures were determined using ESI–MS spectrometry, 1H NMR spectroscopy, and single-crystal X-ray diffraction. The results showed that the ligands 2-(4-nitrophenyl)-4-phenylquinolin-8-ol (HOQ) and N,N′-bis(2-hydroxybenzylidene)benzene-1,4-diamine (H2BS) were deprotonated by triethyl-amine, forming the counter-ion Et3NH+, which interacts via an N—H...O hydrogen bond with the ligand. The ZnII atoms have a distorted trigonal–pyramidal (ZnOQ) and distorted tetrahedral (ZnBS) geometries with a coordination number of four, coordinating with the ligands via N and O atoms. The N atoms coordinating with ZnII correspond to the heterocyclic nitrogen for the HOQ ligand, while for the H2BS ligand, it is the nitrogen of the imine (CH=N). The crystal packing of ZnOQ is characterized by C—H...π interactions, while that of ZnBS by C—H...Cl interactions. The emission spectra showed that ZnBS complex exhibits green fluorescence in the solid state with a small band-gap energy, and the ZnOQ complex does exhibit non-fluorescence.

Medicinal chemistry insights in neuronal nitric oxide synthase inhibitors containing nitrogen heterocyclic compounds: a mini review.

Many scientific reports over the last two decades have focused on the discovery and development of novel nNOS inhibitors. The structural identity of isoforms, bioavailability, pharmacokinetic, and safety profile issues remain major obstacles in the discovery of more potent and selective nNOS inhibitors. This review aims to provide an in-depth overview of the molecular interaction patterns between nNOS active site and inhibitors containing structurally diverse nitrogen heterocyclic compounds and highlight the structural properties needed to develop selective nNOS inhibitors. Previously published data allowed the usage of the structure-driven approach in the designing of selective nNOS inhibitors, which relies on the specific structural features required to achieve isoform-selectivity towards nNOS. The incorporation of chiral pyrrolidine ring, two aminopyridine heads, or a specific amino tail group, along with the inhibitor's capacity to adopt the curled conformation in the nNOS environment significantly strengthens the molecular interaction between the inhibitor and nNOS residues by forming specific electrostatic interactions and non-bonded contacts that are vital for isoform selectivity. Additional structure-activity relationship investigations are necessary to elucidate more structural characteristics that will ultimately resolve the exact structural basis required for isoform-selective inhibition of nNOS.

Phosphorescent cyclometalated Ir(III) complexes with fluoranthene unit and their near-infrared (NIR) OLEDs showing NIR% higher than 99 %

With the aim to design and synthesize cyclometalated Ir(III) complexes with near-infrared (NIR) emission, a series of ppy-type ligands with fluoranthene unit have been synthesized bearing different aromatic nitrogen heterocycles of isoquinoline, quinoline, pyridine and benzo [d]thiazole. With these organic ligands, four [Ir (ppy)2 (acac)] complexes are prepared named as IrFTIQ, IrFTQL, IrFTPY and IrFTBZ. In solution, IrFTIQ can emit NIR phosphorescence at 738 nm, while IrFTQL (ca. 692 nm), IrFTPY (ca. 670 nm) and IrFTBZ (ca. 690 nm) are typical deep-red emitters. It should be noted that all these fluoranthene-based cyclometalated Ir(III) complexes show good electrochemical stability indicated by their reversible redox procedures. When doped in the emission layer of OLEDs, IrFTIQ and IrFTBZ can furnish NIR electroluminescence (EL) at 748 nm and 700 nm, respectively, while the devices with IrFTPY as emitter can furnish deep-red EL. Critically, the optimized OLED doped with IrFTIQ can achieve maximum external quantum efficiency (EQE) as high as 5.01 % and a radiance up to 6284 mW Sr−1 m−2. Critically, the NIR OLEDs based on IrFTIQ can furnish EL with NIR component (NIR%) of a total spectrum > 99 %. All these encouraging results definitely demonstrate the effectiveness of our molecular design strategy for the new-type Ir(III) NIR phosphorescent complexes and the great potential of the fluoranthene group in developing high-performance Ir-based NIR phosphors for OLEDs.

Rational design and synthesis of new pyrrolone candidates as prospective insecticidal agents against Culex pipiens L. Larvae.

As a result of its high reactivity, furan-2(3H)-one derivative 2 can be selected as a versatile and suitable candidate for building of novel nitrogen heterocyclic compounds. Consequently, furan-2(3H)-one derivative 2 and some nitrogen nucleophiles were utilized as starting materials for the formation of new pyridazinone and pyrrolone derivatives bearing naphthalene moiety. The continuous buildup of insecticide resistance is the main obstacle facing pest control measures. Pyrrole-based insecticides are a favourable choice due to their unique mode of action and no cross-resistance with traditional neurotoxic insecticides. The larvicidal activities of pyrrolone derivatives were assessed against field and laboratory strains of Culex pipiens larvae in comparison with chlorfenapyr (pyrrole insecticide). Compounds 17 (21.05µg/mL) > 9 (22.81µg/mL) > 15 (24.39µg/mL) > 10 (26.76µg/mL) > 16 (32.09µg/mL) were most effective against lab strain of C. pipiens larvae relative to chlorfenapyr (25.43µg/mL). While in field strain, 17 and 15 were the most toxic compounds followed by 9 > 10 > 16 > 2 with LC50 of 9.87, 10.76, 11.52, 12.68, 15.32 and 18.37µg/mL, respectively, compared with chlorfenapyr with 14.03µg/mL. The cytochrome P-450 monooxygenase activities were significantly increased in treated larvae of lab and field strains relative to untreated. The great variations in toxicity of the synthesized compounds were interpreted by structure-activity relationship study. The pyrrolone derivatives are effective against field and insecticide-resistant strains. Therefore, they are considered promising compounds to be integrated into pest management programs.

Highly Chemoselective Synthesis of α, α-Dideuterio Amines by the Reductive Deuteration of Thioamides Using Mild SmI2-D2O.

An efficient and chemoselective protocol for the single-electron-transfer (SET) reductive deuteration of thioamides using SmI2 and D2O is reported. This method uniquely produces α,α-dideuterio amines via a thio-ketyl radical intermediate without generating alcohol byproducts, distinguishing it from the SET reduction of amides. The inherent high reactivity of thioamides obviates the need for ligands like Et3N to improve the reducing power of SmI2, thereby enabling milder reaction conditions that are compatible with a broad range of sensitive functional groups. This protocol tolerates both primary and secondary aliphatic and aromatic thioamides, leading to the synthesis of 27 α,α-dideuterio amines and valuable deuterated nitrogen heterocycles with >95% deuterium incorporations.

A Review on Recent Synthesis and Diverse Biological Activities of Isoquinolone

Abstract: Isoquinolone scaffolds are among the most important core structures of nitrogen heterocyclic compounds, which possess vital roles in biological and physiological activities such as anti-tumor, anti-microbial, anti-leukemic, anti-malaria, anti-dengue, anti-HIV and anti-bacterial. Over the years, multiple studies have been done to synthesize these isoquinolone derivatives, and several authors have reported on various methods and synthetic routes to produce the target skeletons of isoquinolones. Therefore, many scientific communities have developed these compounds as the intended structure and evaluated their biological activities. Thus, this review confers several information on isoquinolone analogue synthetic strategies and their biological effects on mosquito- borne diseases.

Emergence of a distinct mechanism of C-N bond formation in photoenzymes.

C-N bond formation is integral to modern chemical synthesis due to the ubiquity of nitrogen heterocycles in small-molecule pharmaceuticals and agrochemicals. Alkene hydroamination with unactivated alkenes is an atom economical strategy for constructing these bonds. However, these reactions are challenging to render asymmetric when preparing fully substituted carbon stereocenters. Here, we report a photoenzymatic alkene hydroamination to prepare 2,2-disubstituted pyrrolidines by a Baeyer-Villiger Monooxygenase. Five rounds of protein engineering afforded a mutant, providing excellent product yield and stereoselectivity. Unlike related photochemical hydroaminations, which rely on the oxidation of the amine or alkene for C-N bond formation, this work exploits a through-space interaction of a reductively generated benzylic radical and the nitrogen lone pair. This antibonding interaction lowers the oxidation potential of the radical, enabling electron transfer to the flavin cofactor. Experiments indicate that the enzyme microenvironment is essential in enabling a novel C-N bond formation mechanism with no parallel in small molecule catalysis. Molecular dynamics simulations were performed to investigate the substrate in the enzyme active site which further support this hypothesis. This work is a rare example of an emerging mechanism in non-natural biocatalysis, where an enzyme has access to a mechanism that its individual components do not. Our study showcases the potential of enhancing emergent mechanisms using protein engineering to provide unique mechanistic solutions to unanswered challenges in chemical synthesis.

Supramolecular cyclodextrin complexes of biologically active nitrogen heterocycles

The review is devoted to the rapidly developing field of modern supramolecular chemistry - cyclodextrin complexes of biologically active nitrogen heterocycles, such as piperidines, piperazines, morpholines and pyridines. Interest in cyclodextrin complexes is growing due to the search and construction of supramolecular assemblies for targeted drug delivery. The latter is achieved as a result of supramolecular self-assembly, based on the principles of molecular recognition, and is one of the areas of modern chemistry, leading to the creation of new materials with new properties. This review fully demonstrates the ongoing scientific and practical interest in the problem of encapsulation with cyclodextrins, including nanoencapsulation. Encapsulation with cyclodextrins provides a wide range of advantages: obtaining solid dosage forms from liquid ones, stabilizing and protecting active substances from the adverse effects of external factors, increasing solubility, increasing bioavailability, reducing toxicity, prolonging action, etc. The presented review includes recent advances in the field of supramolecular complexes of biologically active nitrogen heterocycles with cyclodextrins and concludes with a discussion and identification of future promising directions for research. The review presents the results of supramolecular self-assembly of biologically active azaheterocycles with cyclodextrins.

Three-Component Synthesis of 1-Substituted 5-Aminotetrazoles Promoted by Bismuth Nitrate.

A nontoxic bismuth-promoted multicomponent synthesis of 5-aminotetrazoles and bistetrazoles is reported. The reaction of phenyl isothiocyanate, NaN3, and amine (primary aliphatic, aromatic, and aliphatic diamine) promoted by Bi(NO3)3·5H2O under microwave heating affords good yields, short reaction times, simple workup, and purification without column chromatography. A set of diagnostic 1H NMR signals was identified as a guide for quickly elucidating the exclusive (or main) regioisomer formed, with the stronger electron donor group located at heterocyclic nitrogen 1. This regioselectivity is strongly dependent on the electronic density of the amine. It is opposite to that obtained by several thiourea desulfurization methods promoted by thiophilic metals and metal-free protocols.

Novel Cyanide-Containing Porphyrins: Unleashing In Vitro Photodynamic Therapy Potential

Porphyrins, a class of four-pyrrole nitrogen heterocyclic compounds, have been used in photodynamic cancer therapy. In this study, three distinct pyridine cationic porphyrin photosensitizers were synthesized, each possessing unique side chains containing cyanide groups (H2-P1∼H2-P3). These photosensitizers were prepared using innovative synthetic methods. Subsequently, their theoretical photophysical properties were investigated using density functional theory (DFT). Notably, this research revealed that H2-P2 exhibits the smallest band gap (2.3548 eV) and the lowest energy gap (ΔEST =0.67 eV). Simultaneously, it was confirmed that these three photosensitizers could indeed produce singlet oxygen under illumination using DPBF as a singlet oxygen probe. Additionally, TPP was uesed as a reference to calculate the singlet oxygen yield for all three compounds, with H2-P2 demonstrating the highest yield (ΦΔ = 0.74). The experimental results aligned with the theoretical predictions. The phototoxicity and dark toxicity of the three photosensitizers were further evaluated using the MTT test. Remarkably, H2-P2 exhibited the highest phototoxicity toward HepG2 cancer cells (IC50<9.1 nM), while the lowest dark toxicity toward HUVEC cells (IC50>10 μM). These findings were supported by additional experiments involving cell staining and measurement of reactive oxygen species.

Flavor properties of post-heated fermented milk revealed by a comprehensive analysis based on volatile and non-volatile metabolites and sensory evaluation

Existing research on the post-heating processing of fermented milk has primarily focused on single post-heating treatments and the texture, while research on how changes in metabolites during different post-heating treatments affect flavor and sensory properties is limited. This study investigates the changes in volatile metabolites in fermented milk treated at different post-heating temperatures to determine the characteristic aroma types and analyzes the changes in non-volatile metabolites associated with aroma-active compounds or their precursors to clarify the causes of the altered flavor and sensory properties. The results showed that in the 65°C and 75°C treatments, 63 volatile compounds were produced by Strecker degradation, lipid oxidation and esterification to produce ketones and aldehydes. Significantly higher odor activity values for 2,3-butanedione, hexanoic acid, and esters and significantly lower odor activity values for 2-heptanone enhanced the frankincense odors and creaminess of the post-heated fermented milk. With temperatures increasing to 95°C, the increased ketones were primarily 2-heptanone, 2-nonanone, and 2-undecanone that originated from the oxidative decomposition of unsaturated phospholipids at high temperatures. The Maillard reaction of dipeptides produces nitrogenous heterocycles that trigger a caramelized flavor, while organic acids interact with proteins to form complexes that produce astringent flavors. These increase the oxidative off-flavors and reduce the overall palatability. These findings provide a scientific basis for optimizing the post-heating temperature process of fermented milk.

Synthesis and insecticidal assessment of nitrogenous heterocycles derived from 2-pyridone derivative against Culex pipiens L. Larvae

This study reports the synthesis of a novel 1,6-diamino-4-(2,4-dichlorophenyl)-2-oxo-1,2-dihydropyridine-3,5-dicarbonitrile (1) and its subsequent functionalization to yield a library of diverse heterocycles (2-10). The nucleophilicity of compound 1 was exploited to react with various electrophiles to afford a range of structurally enriched derivatives. The structures of all synthesized heterocycles were confirmed by elemental analysis and spectroscopic techniques as (FT-IR, 1H-NMR, 13C-NMR, and mass spectroscopy). Bioassays revealed significant larvicidal activity against mosquito larvae (Culex pipiens L.) for compounds 1-4, 6, 7 and 9. In silico docking studies suggest a potential mode of action through acetylcholinesterase (AChE) inhibition, potentially explaining the observed larvicidal effect. Additionally, interactions with other neuroreceptors were predicted. Finally, analyzing of the structure activity relationship (SAR) of the novel constructed heterocycles gives us a lot of interesting promising results for developing novel and sustainable mosquito control strategies.

Synthesis, spectroscopic characterization, antimicrobial activity, and computational studies of five and/or six heterocyclic nitrogen rings linked to thienopyrazole moiety

A new series of thienopyrazoles linked to five and/or six heterocyclic nitrogen rings such as pyrazole, triazole-3-thione, oxadiazole, thiazole-2-thione and/or pyrimidone moieties was synthesized starting from 5-amino-1,3-diphenyl-1H-thieno[3,2-c]pyrazole-6-carboxylic acid hydrazide as a key precursor. For the synthesis of new thienopyrazoles 2-13, the carboxylic acid hydrazide derivative 1 served as a crucial intermediary. These novel heterocyclic structures were confirmed by analytical and spectroscopic methods (m.p., IR, 1H-NMR, 13C-NMR, and MS). The new compounds 2-13 were evaluated for their antimicrobial activity to identify new drug candidates to combat diseases caused by microbial strains. Against numerous bacterial and fungal strains, certain derivatives of the produced compounds 9 and 11 demonstrated impressive antimicrobial activity. Besides, molecular docking of the newly compounds was conducted against methicillin-resistant Staphylococcus aureus (MRSA) (2 × 3f.pdb). Among the series, compounds 9 and 11 exhibited the best binding affinity towards the target enzyme -10.1 and -10.5 kcal/mol, respectively. The optimized structures and molecular orbitals of the best docked compounds were predicted using DFT (Density Functional Theory) analysis. Our findings represented that both derivatives 9 and 11 could be utilized for development antimicrobial drug candidates.

Bibliometric Analysis of Pyrimidine Compounds with Anti-cancer Activity: Research Trends from 2015 to 2023

Cancer remains one of the most pervasive diseases in the world, globally, leading to millions of fatalities annually. Currently, numerous anti-cancer treatments are available to address the various types of cancer. Pyrimidine, a class of heterocyclic nitrogenous compounds, holds substantial promise in anti-cancer drug development due to its structural similarity to the nucleotide base pairs found in DNA and RNA. This work aimed to conduct a bibliometric analysis of studies on pyrimidine compounds with anti-cancer characteristics. Using the Scopus database, we examined literature published between 2015 and 2023, explicitly concentrating on pyrimidine derivatives as potential anti-cancer agents. Data analysis such as network analysis, co-occurrence, and visualization were conducted utilizing VOSviewer 1.6.13. Nine hundred twenty-two papers altogether, including reviews and original research, discussing the anti-cancer activity of pyrimidine compounds were identified within the specified timeframe up to January 10, 2023. Among these, 922 journal articles were selected for further analysis. Results show that Egypt led in research productivity with 267 articles (28.96%), followed by India with 234 articles (25.38%), and China with 163 articles (17.68%). Cairo University in Egypt ranked first in institutional productivity with 9 articles (0.98%), while the journal Bioorganic Chemistry was the most prolific, publishing 62 articles (6.72%) on pyrimidine compounds with anti-cancer activity. The notable increase in publications on the anti-cancer activity of pyrimidine compounds in recent years underscores the significant interest they have garnered from both pharmaceutical and academic researchers. The data presented in this study will serve as a foundational reference for future comparative studies in this area.

Effects of imidazole derivatives on cellular proliferation and apoptosis in myeloid leukemia.

Acute promyelocytic leukemia (APL) is the sub-type of Acute myeloid leukemia (AML) which is described by differentiation block at promyelocytic stage and t(15; 17) translocation with All trans retinoic acid (ATRA) and arsenic trioxide (ATO) as standard treatments. Chronic myeloid leukemia (CML) translocation t (19; 22) causes a rise in granulocytes and their immature precursors in the blood. Different mutations cause resistance to first-line tyrosine kinase therapies in CML. Beside drug resistance, leukemia stem cells (LSC) are critical resources for relapse and resistance in APL and CML. The drug toxicity and resistant profile associated with LSC and current therapeutics of APL and CML necessitate the development of new therapies. Imidazoles are heterocyclic nitrogen compounds with diverse cellular actions. The purpose of this research was to assess the anti-leukemic properties of four novel imidazole derivatives including L-4, L-7, R-35, and R-NIM04. Pharmacological and biochemical approaches were used which showed that all four imidazole derivatives interfere with the NB4 cells proliferation, an APL cell line, while only L-7 exhibit anti-proliferative activity against K562 cells, a CML cell line. The anti-proliferative effect of imidazole derivatives was linked to apoptosis induction. Further real-time polymerase chain reaction (RT-PCR) analysis revealed downregulation of AXL-Receptor Tyrosine Kinase (AXL-RTK) and target genes of Wnt/beta-catenin pathway like c-Myc, Axin2 and EYA3. An additive effect was observed after combinatorial treatment of L-7 with standard drugs ATRA or Imatinib on the proliferation of NB4 and K562 cells respectively which was related to further downregulation of target genes of Wnt/beta catenin pathway. Imidazole derivatives significantly reduce proliferation of NB4 and K562 cells by inducing apoptosis, down regulating of AXL-RTK and Wnt/β-catenin target genes.

Delivery of N-heterocyclic drugs, acids, phenols, and thiols via Tailor−made Self−immolative linkers

Heterocyclic drugs display diverse pharmacological activities and metabolic stability. However, their poor solubility and pharmacokinetic properties often compromise bioavailability and clinical outcomes. Nevertheless, the prodrug approach provides a viable strategy to overcome unwanted attributes of drug candidates. In this proof-of-concept study, we report the synthesis and biological evaluation of glycol methylene-bridged phosphate (GMBP) prodrugs developed for heterocyclic drug delivery. Through methylene bridging, the heterocyclic nitrogen was directly attached to the phosphate, whereas the glycol moiety enabled drug release via cyclization, as confirmed by 31P NMR spectroscopy. Additional prodrugs of carboxylic acids, phenols, and thiols confirmed the broad application scope of our GMPB approach. Heterocyclic GMBP prodrugs were stable in aqueous buffers and activated by phospholipase CAL-B in vitro. Select prodrugs, including zidovudine prodrug 33, were even more potent (3 nM on HIV-1) than the parent compound. These findings demonstrate that our GMBP approach is not only feasible but also highly versatile.

A Fragment-Based Screen for Inhibitors of Escherichia coli N5-CAIR Mutase.

Although purine biosynthesis is a primary metabolic pathway, there are fundamental differences between how purines are synthesized in microbes versus humans. In humans, the purine intermediate, 4- carboxy-5-aminoimidazole ribonucleotide (CAIR) is directly synthesized from 5-aminoimidazole ribonucleotide (AIR) and carbon dioxide by the enzyme AIR carboxylase. In bacteria, yeast and fungi, CAIR is synthesized from AIR via an intermediate N5-carboxyaminoimidazole ribonucleotide (N5-CAIR) by the enzyme N5-CAIR mutase. The difference in pathways between humans and microbes indicate that N5-CAIR mutase is a potential antimicrobial drug target. To identify inhibitors of E. coli N5-CAIR mutase, a fragment-based screening campaign was conducted using a thermal shift assay and a library of 4,500 fragments. Twenty-eight fragments were initially identified that displayed dose-dependent binding to N5-CAIR mutase with Kd values ranging from 9-309 μM. Of the 28, 14 were obtained from commercial sources for retesting; however, only 5 showed dose-dependent binding to N5-CAIR mutase. The five fragments were assessed for their ability to inhibit enzyme activity. Four out of the 5 showed inhibition with Ki values of 4.8 to 159 μM. All fragments contained nitrogen heterocycles with 3 out of the 4 containing 5-membered heterocycles like those found in the substrate of the enzyme. The identified fragments show similarities to compounds identified from studies on B. anthracis N5-CAIR synthetase and human AIR carboxylase suggesting a common pharmacophore.

Formal [2σ + 2σ]-Cycloaddition of Aziridines with Bicyclo[1.1.0]butanes: Access to Enantiopure 2-Azabicyclo[3.1.1]heptane Derivatives.

Saturated nitrogen heterocycles are among the most significant structural components in small-molecule pharmaceuticals. Herein, a protocol for the construction of enantiopure 2-azabicyclo[3.1.1]heptane derivatives by a stereospecific intermolecular formal cycloaddition of aziridines with bicyclo[1.1.0]butanes is described. The reaction is run by using B(C6F5)3 as a catalytic additive to give access to a library of enantiopure 2-azabicyclo[3.1.1]heptane derivatives (37 examples) under mild and operationally simple conditions. Successful scale-up reactions, mechanistic experiments, density functional theory (DFT) calculations and synthetic applications are presented.

Effect of reactive oxygen species (ROS) produced by pyridine and quinoline on NH4+-N removal under phenol stress: The shift of nitrification pathway and its potential mechanisms

Pyridine and quinoline are typical nitrogenous heterocyclic compounds with different structures that are found in coking wastewater. However, neither the corresponding mechanism nor its effect on the degradation of NH4+-N under phenol stress is known. In this study, the effects of pyridine and quinoline degradation on NH4+-N removal under phenol stress were evaluated using three lab-scale sequencing batch reactors. The average NH4+-N removal efficiencies of the reactors were 99.46 %, 88.86 %, and 98.64 %. With the increased concentration of pyridine and quinoline, NH4+-N and NO3--N accumulated to 58.37 mg/L and 141.37 mg/L, respectively, due to the lack of an electron donor and anaerobic environment. The addition of pyridine and quinoline significantly improved antioxidant response and altered the nitrification pathway. The nitrification process shifted from the mediation of amo and hao to the mediation of Ncd2 due to oxidative stress induced by pyridine and quinoline. Furthermore, oxidative stress interferes with the metabolism of carbon sources, resulting in decreased biomass. These results provide a new perspective for coking wastewater treatment processes.

Tandem diazotization/cyclization approach for the synthesis of a fused 1,2,3-triazinone-furazan/furoxan heterocyclic system.

A straightforward protocol for the synthesis of a previously unknown [1,2,5]oxadiazolo[3,4-d][1,2,3]triazin-7(6H)-one heterocyclic system was developed. The described approach is based on tandem diazotization/azo coupling reactions of (1,2,5-oxadiazolyl)carboxamide derivatives bearing both aromatic and aliphatic substituents. The NO-donor ability of the synthesized furoxano[3,4-d][1,2,3]triazin-7(6H)-ones was additionally evaluated. The elaborated method provides access to novel nitrogen heterocyclic compounds with potential applications as drug candidates or thermostable components of functional organic materials.