Journal of Heterocyclic Chemistry最新文献

1,2,3-Triazoles have emerged as essential scaffolds in medicinal chemistry due to their versatile biological activities and bio-isosteric properties. Several triazole-containing drugs have received FDA approval, with many others undergoing clinical evaluation, highlighting their significance in drug discovery. In recent years, substantial progress has been made in developing efficient and sustainable synthetic methodologies for 1,2,3-triazoles. This review provides a comprehensive overview of these advances, covering strategies such as transition metal-catalyzed, organocatalyzed, heterogeneous, ionic liquid-mediated, and metal-free approaches from early 2018 to the present. The discussion emphasizes innovative modifications to established protocols and the exploration of novel reaction pathways that enable structural diversification. This compilation serves as a valuable resource for researchers aiming to expand the synthetic utility of triazole derivatives for pharmaceutical and material science applications.

Depression is a prevalent and debilitating mental health disorder, driving the urgent need for novel and effective therapeutic agents. Piperazine–oxadiazole hybrids have gained significant attention in antidepressant drug discovery due to their unique structural features, favorable CNS pharmacokinetic profile, and pharmacological potential. This review explores the structural significance and recent advancements in these hybrid molecules, focusing on their designed strategies, synthetic approach, and antidepressant activity, with a particular focus on their interactions with key enzymes such as monoamine oxidase. This review also highlights recent advancements in the development and creation of piperazine derivatives and oxadiazole derivatives as potential antidepressants, focusing on their interactions with various receptors and enzymes. Overall, this work underscores the potential of piperazine–oxadiazole hybrids as a promising avenue for the next generation of antidepressant therapeutics. The structural optimization of both piperazine – oxadiazole hybrids is discussed with the help of electron-withdrawing and electron-donating groups. The length and flexibility of linkers between piperazine and oxadiazole can dictate spatial orientation and optimize receptor interaction. The recent advancements in piperazine and oxadiazole derivatives and their hybrids as antidepressants are discussed from 2019 to 2024. However, further research and clinical investigations are warranted to fully harness their therapeutic potential in managing depression.

A new series of fused pyrazole-based heterocycles was synthesized from 3-pyridyl hydrazine and benzylidene malononitrile via cyclization with diverse nucleophiles. The resulting pyrazolo[3,4-d]pyrimidines, thiazoles, thiazines, and thiazolidinones were characterized by IR, ¹H-NMR, and elemental analysis. Several derivatives displayed potent antimicrobial activity, notably thiazolidinone (12), dithione (9), and diphenyl-pyrazolopyrimidine-thione (19b), with MICs as low as 3.125 μg/mL, comparable to standard drugs. Structure–activity analysis revealed that fused frameworks and sulfur-containing groups enhanced bioactivity. Molecular docking against the bacterial ribosomal protein (PDB ID: 3g7b) confirmed strong binding, with compound 19b showing the best interaction (ΔG = −5.75 kcal/mol). These findings highlight fused pyrazole–sulfur scaffolds as promising candidates for antimicrobial drug development.

Selenadiazoles, a unique class of selenium-containing heterocyclic compounds, have attracted considerable interest due to their exceptional structural features and versatile electronic properties. These compounds have demonstrated significant potential across various domains, including medicinal chemistry, materials science, and catalysis. In the realm of pharmaceutical research, selenadiazoles exhibit noteworthy biological activities, such as antimicrobial, anticancer, and antioxidant effects. These properties are largely attributed to the redox-active selenium center within their molecular framework, which enables modulation of oxidative stress and enzyme activity. As a result, selenadiazoles have emerged as promising candidates for drug discovery and therapeutic development. Beyond their biomedical applications, selenadiazoles play a crucial role in materials science, particularly in the design of organic semiconductors, optoelectronic devices, and luminescent materials. Their tunable electronic characteristics and inherent stability make them valuable building blocks for advanced materials with applications in organic electronics and photonic technologies. In addition, selenadiazoles have proven to be efficient catalysts in organic synthesis, facilitating environmentally benign and selective chemical transformations. Their catalytic efficiency and reusability further underscore their importance in green chemistry. This review presents a comprehensive overview of the synthesis, structural attributes, and functional applications of selenadiazoles, with a particular emphasis on recent advances in their development. A total of 352 selenadiazole compounds are discussed, encompassing all major structural types, including 1,2,3-selenadiazoles, 1,2,4-selenadiazoles, 1,2,5-selenadiazoles, and 1,3,4-selenadiazoles. The article provides an in-depth analysis of the latest synthetic methodologies developed between 2015 and 2025, highlighting emerging trends and underscoring the growing significance of selenadiazoles in contemporary scientific research.

The design and synthesis of novel indole-linked 1,2,3-triazole hybrids targeting Mycobacterium tuberculosis (H37Rv). The methods are summarized, highlighting the use of CuAAC reactions for synthesis and characterization via HRMS, NMR, and in vitro anti-tubercular screening. Key results emphasize the potent activity of para-nitro and cyano-substituted compounds (MIC = 1.56–3.125 μg/mL), comparable to ethambutol, supported by molecular docking studies revealing strong binding interactions with MtbAT protein. The significance of these findings is underscored by their potential to address drug-resistant TB, with ADMET profiles suggesting promising drug-like properties.

In this work, 13 novel ciprofloxacin hybrid molecules containing active groups such as coumarin, triazole, pyridine, and benzimidazole were designed, synthesized, and screened for their antibacterial activities against Gram-positive (B. megaterium, B. subtilis, E. faecalis, and S. aureus) and Gram-negative (E. coli, P. aeruginosa, E. cloacae, Y. pseudotuberculosis, and S. typhimurium) bacteria. The obtained results demonstrated that the general synthesized compounds showed similar or better activities than the standard drug ciprofloxacin. The structure–activity relationship (SAR) studies have showed that the combination of benzimidazole, azabenzimidazole, triazole, and coumarin moieties with ciprofloxacin increased the antibacterial activities against most of the tested microorganisms. The characterization studies were done by using IR, ¹H-NMR, ¹³C-NMR, LC–MS/MS, and elemental analysis technique.

This study describes an effective method for synthesizing derivatives using piperidinium borate, a conjugate organic base catalyst. The methodology was tested with various aromatic aldehydes, substituted aromatic aldehydes, and aliphatic aldehydes with malononitrile and Kojic acid in EtOH: Water (1:1) as a greener solvent. The recovery of the catalyst from the aqueous layer was established for five cycles without loss of catalytic activity. This approach offers various benefits to synthesized pyran-annulated heterocycles, such as smooth reaction conditions, shorter reaction time, easy availability of raw materials, and excellent product yield.

Pyrazoles constitute a pivotal heterocyclic scaffold found in anti-inflammatory, anticancer, anticonvulsant, antidepressant, and anti-infective agents, highlighting their significance in pharmaceutical development. This review critically examines two principal synthetic methodologies: (i) the condensation of 1,3-dicarbonyl compounds and conjugated π-systems with hydrazine derivatives, focusing on substrate scope, regioselectivity challenges, and mechanistic underpinnings, and (ii) [3 + 2] cycloaddition strategies involving alkynes or activated olefins with 1,3-dipoles, emphasizing catalyst systems and functional group tolerance. Recent innovations, including solvent-free microwave-assisted synthesis, visible-light photocatalysis, and flow chemistry, are highlighted for their roles in improving atom economy and scalability of pyrazole frameworks. By comparing classical methods with emerging green and continuous synthesis techniques, this review provides practical insights to facilitate the design of efficient and sustainable pyrazole syntheses tailored for pharmaceutical and materials applications.

For the first time, in the present communication we studied intramolecular cyclization of (het)arylbisallomaltols under the action of acidic reagents. It was shown that the presented transformation provides efficient access to structurally diverse heterocyclic systems, with the product outcome determined by the nature of the (het)aryl substituent in the starting materials. In most cases, the investigated process affords previously unreported 4H-dipyrano[3,2-b:2′,3′-e]pyran-4,6(10H)-diones via the binding of hydroxyl groups of two allomaltol units. At the same time, the presence of active functional groups in the (het)aryl moiety alters the reaction pathway, resulting in the formation of condensed pyrano[3,2-b]pyran-4(8H)-ones. These findings enabled the development of general synthetic strategies for diverse polycyclic pyran-4-one-containing frameworks. Additionally, the attempt to synthesize a benzimidazolyl-containing bisallomaltol unexpectedly led to the formation of benzo[4,5]imidazo[1,2-a]pyridin-1(5H)-one derivative. The key representatives of the obtained products were unambiguously confirmed by X-ray analysis.

The reaction of 1-benzyl- and 1-(2-phenylethyl)- 3-methyl-5-pyrazolone with POCl₃ and DMF affords N,N-dimethylaminothylidene derivatives that in acid or basic medium can be transformed into the corresponding aldehydes at carbon 4 of the heterocycle. The dimethylenamine can also be more easily obtained by reacting pyrazolones with the dimethyl acetal of N,N-dimethylformamide. Starting from the aldehydes or the N,N-dimethylenamines, it is possible to obtain new enamines. The advantages of using dimethylenamines are the absence of the enol as an undesired byproduct and that there is no need to prepare the aldehyde to obtain Schiff bases. Overall, the yields can be classified as acceptable. The aldehydes can be described as 5-hydroxypyrazole-4-carbaldehydes in chloroform solutions, but in solid phase they are dicarbonyl compounds. The Schiff bases exhibit an enamine structure in chloroform solution and in solid phase.