Search Results (512)

Photocatalytic synthesis of heterocycles has emerged as a versatile strategy in organic synthesis. Among various heterocycles, five membered heterocycles such as pyrroles, indoles and their derivatives have great significance based on their pharmaceutical applications. Diverse photocatalysts have shown great potential in synthesis of nitrogen heterocycles either through radical-based mechanism or via energy transfer pathway. Compared to other synthesis routes, the photocatalytic approach offers unique advantages including green synthesis, one step reaction and approaching the challenging reaction to prepare nitrogen heterocycles. Tuning redox potential or tailoring triplet state energies of photocatalysts can play crucial role in selective and efficient synthesis of nitrogen heterocycles. In this review we have briefly covered the latest developments demonstrated for photocatalytic synthesis of five membered nitrogen heterocycles including pyrroles and indoles and their derivatives. We also discuss the existing challenges, bottlenecks and the future outlook in this field, aiming to advance photocatalytic strategies of producing five membered nitrogen heterocycles as valuable tools in modern synthetic chemistry. Full article

Nitrogen-containing heterocycles are essential compounds in nature, and their structural and functional diversity inspired the synthesis of a wide range of derivatives with diverse applications as pharmaceuticals, agrochemicals, dyes, polymers, cosmetics, etc. Among them, N-fused heterocycles represent an important category, due to their high potential as biologically active agents. Pyrazolo[5,1-c][1,2,4]triazoles, a class of nitrogen heterobicycles, have multiple applications as dyes and pigments. Also, a number of compounds containing this structure have been investigated for their biological activities. All the main experimental results published in the literature (both articles and patents) regarding the latter are summarized in this review. Full article

This review summarises the possible applications and basic methodologies for the synthesis of six-membered polyazo heterocycles, namely, diazines, triazines, and tetrazines. The time period covered by the analysed works ranges from the beginning of the 20th century to the present day. This period was chosen because it was during this time that synthetic chemistry, as defined by physicochemical research methods, became capable of solving such complex problems as efficiently as possible. The first part of the review describes the applications of polyazo heterocyclic compounds, whose frameworks are found in the composition of drugs, dyes, and functional molecules for materials chemistry, as well as in a wide variety of natural compounds and their synthetic analogues. The review also systematises the methods for assembling six-membered aromatic polyazo heterocycles, including intramolecular and sequential cyclisation, which determine the possible structural and functional diversity based on the presence and arrangement of nitrogen atoms and the position of the corresponding substituents. Full article

Fused and spiro nitrogen-containing heterocycles play an important role as structural motifs in numerous biologically active natural products and pharmaceuticals. The review summarizes various approaches to the synthesis of three-, four-, five-, and six-membered fused and spiro heterocycles with one or two nitrogen atoms. The assembling of the titled compounds via cycloaddition, oxidative cyclization, intramolecular ring closure, and insertion of sextet intermediates—carbenes and nitrenes—is examined on a vast number of examples. Many of the reactions proceed with high regio-, stereo-, or diastereoselectivity and in excellent, up to quantitative, yield, which is of principal importance for the synthesis of chiral drug-like compounds. For most unusual and hardly predictable transformations, the mechanisms are given or referred to. Full article

This study investigates how phospholipid headgroups influence passive membrane penetration and structural impact of four nitrogen-, sulfur-, and oxygen-containing heterocycles (NSO-HETs)—N-methyl-2-pyrrolidone (PIR), 1,4-dioxane (DIOX), oxane (OXA), and phenol (PHE). Using all-atom molecular dynamics simulations combined with Accelerated Weight Histogram free energy calculations, the passive transport of NSO-HETs across DPPC, DPPE, DPPA, and DPPG bilayers was characterized. DPPG showed the highest membrane affinity, increasing permeability (logP_memb/bulk) by 27–64% compared to DPPE, associated with the lowest permeability and tightest lipid packing. Free energy barriers are also decreased in DPPG relative to DPPE; PIR’s central barrier dropped from 19.2 kJ/mol (DPPE) to 16.6 kJ/mol (DPPG), while DIOX’s barrier decreased from 7.2 to 5.2 kJ/mol. OXA exhibited the lowest central barriers (1.2–2.2 kJ/mol) and uniquely accumulated at higher concentrations in the bilayer center than in bulk water, with free energy ranging from −3.4 to −5.9 kJ/mol. PHE and OXA caused significant bilayer thinning (up to 11%) and reduced lipid tail order, especially in DPPE and DPPA. Concentration effects were most pronounced in DPPE, where high solute loading disrupted lipid order and altered free energy profiles. These results highlight the crucial role of headgroup identity in modulating NSO-HET membrane permeability and structural changes. Full article

Benzothiazole derivatives have emerged as being highly significant in drug discovery due to their versatile biological activities and structural adaptability. Incorporating nitrogen and sulfur, this fused heterocyclic scaffold exhibits wide-ranging pharmacological properties, including anticancer, antimicrobial, anti-inflammatory, antidiabetic, neuroprotective, and diagnostic applications. A diverse set of clinically approved and investigational compounds, such as flutemetamol for Alzheimer’s diagnosis, riluzole for ALS, and quizartinib for AML, illustrates the scaffold’s therapeutic potential in varied applications. These agents act via mechanisms such as enzyme inhibition, receptor modulation, and amyloid imaging, demonstrating the scaffold’s high binding affinity and target specificity. Advances in synthetic strategies and our understanding of structure–activity relationships (SARs) continue to drive the development of novel benzothiazole-based therapeutics with improved potency, selectivity, and safety profiles. We also emphasize recent in vitro and in vivo studies, including drug candidates in clinical trials, to provide a comprehensive perspective on the therapeutic potential of benzothiazole-based compounds in modern drug discovery. This review brings together recent progress to help guide the development of new benzothiazole-based compounds for future therapeutic applications. Full article

Heterocyclic compounds are a common subject in the field of medicinal chemistry due to their numerous pharmaceutical applications. Among these, nitrogen- and oxygen-containing five-membered heterocyclic rings, namely oxazole and isoxazole, are particularly significant, exhibiting a broad spectrum of biological activities. Molecular hybridization, the process that enables the fusion of bioactive scaffolds, is a powerful strategy for the development of novel compounds characterized by enhanced or multitarget activities. This review focuses on hybrids incorporating linked oxazole and/or isoxazole moieties (i.e., isoxazole–oxazole and isoxazole–isoxazole hybrids), drawing upon peer-reviewed research articles and international patents from 1995 to the end of 2024. The overview systematically presents the diverse biological activities reported for the isoxazole–(iso)oxazole hybrids, including anticancer, antibacterial, antitubercular, anti-inflammatory, and antidepressant effects, alongside their corresponding chemical structures. Our analysis of the literature highlights the structural versatility and therapeutic potential of this important class of heterocyclic hybrids. Full article

Four novel crystalline architectures based on benzo[c]cinnolininium trifluoromethanesulonate salts, [C₁₂H₉N₂]⁺[CF₃SO₃]⁻, have been isolated as single-crystals, and their structures have been determined by X-ray diffraction analysis. The formation of the new salts results from reactions involving the dimeric hydroxo di-n-butylstannane trifluoromethanesulfonato complex [n-Bu₂Sn(OH)(H₂O)(CF₃SO₃)]₂ (1) and benzo[c]cinnoline (C₁₂H₈N₂, BCC). Organic salts I, II, III, and IV were crystallized through slow evaporation at room temperature from a mixture of toluene/dichloromethane. The cystallographic structures of I, II, and IV exhibit the presence of monoprotonated benzo[c]cinnolinium cations in interactions with a free benzo[c]cinnoline molecule through N–H···N hydrogen bonding, while for salt III, the monoprotonated cation directly interacts with the CF₃SO₃⁻ anion via an N–H···O interaction. For all four salts, aromatic π-π interactions involving rings of various components (free benzo[c]cinnoline molecule, benzo[c]cinnolinium cation, toluene molecule), combined with weak C–H···O and C–H···F interactions implying the trifluoromethanesulfonate anion, promote the solid-state self-assembly of supramolecular stacks. In parallel to the formation of benzo[c]cinnolinium based-salts, organotin(IV) 1 was converted into a distannoxane compound, ²_∞{[n-Bu₂(μ-OH)SnOSn(μ-η²-O₃SCF₃)n-Bu₂]₂[n-Bu₂(η¹-O₃SCF₃)SnOSn(μ-OH)n-Bu₂]₂} (3), which was also isolated as a single crystal and whose crystallographic structure was previously established by us. Full article

Background: Type 2 diabetes mellitus (T2DM) presents a significant global health challenge, with obesity being a major contributing risk factor alongside genetic and non-genetic elements. Current treatments focus on reducing hyperglycemia and preventing T2DM progression, often involving drug combinations for enhanced efficacy. This study introduces two novel nitrogen-containing heterocyclic scaffolds: neocryptolepine–thiazolidinedione (NC-TZD) 8 and acridine–thiazolidinedione (AC-TZD) 11. Methods: These compounds were synthesized and characterized using various spectroscopic techniques. Their antihyperglycemic and antihyperlipidemic effects were assessed in an obesity-induced zebrafish model. Hyperglycemia was induced by immersing zebrafish in 100 mM glucose monohydrate for two weeks. Fish were then divided into groups receiving either 20 mg or 80 mg of the drugs per kg of body weight, alongside negative and positive control groups. Results: Both doses of hybrids 8 and 11 effectively restored glucose, triglyceride, insulin, and nuclear factor kappa beta (nfκβ) mRNA levels to normal. However, only the lower doses restored peroxisomal acyl-CoA oxidase (acox1) mRNA levels, with higher doses proving less effective. A molecular modeling study supported the antidiabetic potential of hybrids 8 and 11, suggesting interactions with target proteins PPAR-α and acox1. In silico ADMET analysis revealed promising oral bioavailability and drug likeness for both compounds. Conclusions: The findings indicate that both hybrids exhibit significant antihyperglycemic and antihypertriglyceridemic effects, particularly at lower doses. These results highlight the promising therapeutic potential of these novel oral bioavailable compounds in managing T2DM. Further research is warranted to elucidate their mechanisms of action. Full article

This study describes the synthesis of heterocyclic derivatives containing multiple nitrogen atoms serving as important moieties for developing novel antidiabetics through a simple synthetic pathway. We herein describe the synthesis and characterization of novel pyrimidine derivatives using one-pot reactions in a catalyst-free and efficient manner through a two-stage process involving the synthesis of 2-amino-4-hydrazinyl-6-methoxy pyrimidine, followed by a reaction with phenyl isothiocyanate derivatives. The structures of all the new compounds were confirmed via physical and spectral analysis. Furthermore, we evaluated the synthesized pyrimidine derivatives’ biological activities in relation to their potential roles as novel anti-diabetic agents by testing their activity profiles against the enzymes α-glucosidase and α-amylase. Compound 4 expressed the highest level of activity against α-glucosidase and α-amylase, with a greater inhibitory concentration (IC₅₀ of 12.16 ± 0.12 µM and IC₅₀ 11.13 ± 0.12 µM) compared to that of acarbose (IC₅₀ = 10.60 ± 0.17 µM and IC₅₀ = 11.30 ± 0.12 µM), which is widely used as a standard antidiabetic drug. The primary structure activity relationship analysis identified the impact of an electron- withdrawing group, especially with respect to fluorine on inhibitory activity. This was further confirmed in molecular docking studies, which demonstrated that both compounds exhibited similar inhibition patterns and emphasized the significance of incorporating a lipophilic electron-withdrawing substituent on the phenyl ring, along with the 2,4-diaminopyrimidine scaffold. Full article

The imidazo[4,5-b]pyridine scaffold, a versatile heterocyclic system, is renowned for its biological and chemical significance, yet its coordination chemistry with biologically relevant metal dications remains underexplored. This study investigates the proton and metal dication affinities of twelve tetracyclic organic molecules based on the imidazo[4,5-b]pyridine core, focusing on their interactions with Ca(II), Mg(II), Zn(II), and Cu(II). Employing a dual approach of electrospray ionization mass spectrometry (ESI-MS) and density functional theory (DFT) calculations, we characterized the formation, stability, and structural features of metal–ligand complexes. ESI-MS revealed distinct binding behaviors, with Cu(II) and Zn(II) forming stable mono- and dinuclear complexes, often accompanied by reduction processes (e.g., Cu(II) to Cu(I)), while Ca(II) and Mg(II) exhibited lower affinities. DFT analysis elucidated the electronic structures and thermodynamic stabilities, highlighting the imidazole nitrogen as the primary binding site and the influence of regioisomeric variations on affinity. Substituent effects were found to modulate binding strength, with electron-donating groups enhancing basicity and metal coordination. These findings provide a comprehensive understanding of the coordination chemistry of imidazo[4,5-b]pyridine derivatives, offering insights into their potential applications in metalloenzyme modulation, metal-ion sensing, and therapeutic chelation. Full article

Chlorella vulgaris, a unicellular microalga with broad industrial applications, is a valuable source of bioactive compounds, including proteins, pigments, and lipids. However, optimizing its growth and metabolite production remains a challenge. This study investigates the potential of angular 6/6/5/6-annelated pyrrolidine-2,3-diones—structurally complex small molecules resembling alkaloids and 13(14 → 8)abeo-steroids—as novel growth stimulants for C. vulgaris. A series of these compounds (20 structurally diverse derivatives, including 7 previously unreported ones) were synthesized and screened for their ability to enhance microalgal growth. Primary screening identified one compound as a promising candidate, significantly increasing algae cell concentration in microplate cultures. Subsequent validation in flask-scale experiments revealed that this candidate induced a 19% increase in protein content at 1 μmol/L, suggesting potential for protein enrichment in algal biomass. Stability studies of the candidate compound revealed its significant hydrolytic degradation in aqueous media. These findings highlight the potential of angular 6/6/5/6-annelated pyrrolidine-2,3-diones as modulators of microalgal metabolism, offering a new avenue for enhancing C. vulgaris biomass quality, particularly for protein-rich applications in the food and feed industries. Full article

The safety concerns associated with sensitivity issues regarding long nitrogen chain-based energetic compounds, especially for eight or more catenated nitrogen atoms in backbones, need to be resolved. Incorporating specific functional groups represents a key approach for enhancing stability in organic energetic materials. This study reports the synthesis of 1,1′-(diazene-1,2-diyl)bis(4-nitro-1H-1,2,3-triazole-5-carboxamide) (S8), an N8-chain compound featuring strategically placed amide groups. Employing THA(O-tosylhydroxylamine) and KMnO₄, 1,1′-(diazene-1,2-diyl)bis(4-nitro-1H-1,2,3-triazole-5-carboxamide) (S8) was synthesized and underwent N-amination and oxidative azo coupling. Comprehensive characterization, including X-ray diffraction, mechanical sensitivity testing, and theoretical analysis, alongside comparative studies with known N8 compounds, revealed that S8 exhibits unprecedented stability within its class. Among reported N8-catenated nitrogen chain compounds, attributed to the incorporation of the amide functionality, S8 demonstrates the highest impact sensitivity (IS = 10 J) and friction sensitivity (FS = 40 N) while maintaining excellent detonation performance (D = 8317 ms⁻¹, P = 28.27 GPa). This work highlights the amide group as a critical structural part for achieving high stability in sensitive long-nitrogen-chain energetic materials without compromising performance. Full article

Over the past two decades, the copper(I)-catalyzed azide–alkyne 1,3-dipolar cycloaddition (CuAAC), commonly known as click chemistry, and C–H bond activation have gained significant attention and have emerged as key synthetic methodologies. In our efforts to synthesize fused nitrogen-containing heterocycles, we developed a palladium-catalyzed protocol for the synthesis of functionalized 7,10-dihydropyrrolo[3,2,1-ij][1,2,3]triazolo[4,5-c]quinolines and 5,8-dihydrobenzo[3,4][1,2,3]triazolo[4′,5′:5,6]azepino[1,2-a]indoles from suitable bromo-substituted N-propargyl-indoles. The reaction conditions demonstrate broad functional group compatibility including halogen, alkoxyl, cyano, ketone, and ester, affording the target compounds in good to high yields. Full article

Nitrogen-containing heterocycles of 3-pyrrolin-2-one series are widely represented in natural and synthetic compounds, with a broad spectrum of pharmacological activity and considerable potential in medicinal and synthetic organic chemistry. In this communication, we report the previously unknown acid-catalyzed transformation of a N-substituted derivative of 3-pyrrolin-2-one that generates two types of heterocyclic moieties. The reflux of 1-benzyl-3-chloro-5-hydroxy-4-[(4-methylphenyl)sulfanyl]-1,5-dihydro-2H-pyrrol-2-one in toluene in the presence of catalytic amounts of H₂SO₄ resulted in the formation of a mixture of 1-benzyl-3-[(4-methylphenyl)sulfanyl]-1H-pyrrole-2,5-dione and 1-benzyl-7-methyl-1H-benzo[4,5]thieno[3,2-b]pyrrole-2,3-dione. The structures of four novel nitrogen-containing heterocycles were elucidated through IR, NMR spectroscopy and HRMS spectrometry. A new derivative of the fused tricyclic compounds, possessing benzo[b]thiophene and pyrrole-1,2-dione fragments, was also characterized by single-crystal X-ray diffraction. Full article