Heterocyclic Systems Research Articles

Glycerol‐1,2‐carbonate: A mild reagent for the N‐glycerylation of pyrazolecarboxylates

AbstractIn this study, glycerol‐1,2‐carbonate was employed as a convenient reagent for the synthesis of more complex pyrazole‐containing heterocyclic systems. 3‐O‐Tosylated glycerol‐1,2‐carbonate (TGC) was used for alkylation of NH‐pyrazolecarboxylates. The obtained N‐glycerylated pyrazoles were further treated with diverse nucleophiles for 2‐oxo‐1,3‐dioxolane ring cleavage. The synthesized 1‐(2,3‐dihydroxypropyl)‐1H‐pyrazole‐5‐carboxylates were subsequently hydrolyzed and treated with p‐toluenesulfonic acid, yielding a series of 6‐(hydroxymethyl)‐6,7‐dihydro‐4H‐pyrazolo[5,1‐c][1,4]ox‐azin‐4‐ones.

Eco‐sustainable Synthesis of N‐containing Heterocyclic Systems Using Porous Carbon Catalysts

AbstractFrom the most classic carbon materials (CMs) to the advanced ones, all of them integrate a promising catalyst set in terms of sustainability and energy efficiency for a greener future. Different synthetic strategies concerning to the catalytic synthesis of relevant N‐containing heterocycles are herein described to address the great potential of the referred catalysts flying over what has been done and all that remains to be done. Current trends in this field involve structure‐activity relationships establishment also considering the reaction mechanisms understanding and the identification of active catalytic sites, as function of both experimental datasets, emphasizing on operando characterization techniques, and theoretical studies which will significantly contribute to the design of custom‐made catalysts as a new horizon.

In Silico Study of Corticosteroids Drugs

Molecular Docking has become an important component of the drug discovery process. Since first being developed in the 1980s, advancements in the power of computer hardware and the increasing number of and ease of access to small molecule and protein structures have contributed to the development of improved methods, making docking more popular in both industrial and academic settings. In this research Molecular Docking we are perform on triamcinolone and methyl testosterone by using Autodock and Discovery Studio software. QSAR study revealsed that substitution of different electron donating or withdrawing group at different position on triamcinolone and methyl testosterone lead nucleus elaborate change in pharmacological activity. Molecular Docking done by substituting or replacing different group at different position affected the potency of drug on addition of hydroxy, Methyl at different position where reduced the potency of triamcinolone while addition of ether or ester group enhance the potency of triamcinolone. In methyl testosterone, introduction of heterocyclic system into a steroidal nucleus in ring A enhances the potency while removal of hydroxy group, addition of O atom reduces the potency.

Benzo[4’,5’]imidazo[2’,1’:6,1]pyrido[2,3-d]pyrimidines: Past and Present

Synthetic approaches to the construction of the heterocyclic benzo[4’,5’]imidazo[2’,1’:6,1]pyrido[2,3-d]pyrimidine system based on heterocyclizations of substituted benzimidazoles and a new alternative strategy based on 2,4,6-trisubstituted pyrimidinyl-5-propanoic acids are considered. The latter method has been shown to be a successful addition to previously described methods, since it allows one to bypass the significant limitations associated with the use of substituted benzimidazoles and allows the introduction of functional substituents at different positions of the heterocycle that are inaccessible by other methods. The available information on derivatives of this heterocyclic system and their biological properties is summarized.

Chemistry, Synthesis, and Structure Activity Relationship of Anticancer Quinoxalines

Quinoxaline is a fused heterocycle system of a benzene ring and pyrazine ring. It has earned considerable attention due to its importance in the field of medicinal chemistry. The system is of extensive importance due to its comprehensive array of biological activities. Quinoxaline derivatives have been used as anticancer, anticonvulsant, anti-inflammatory, antidiabetic, antioxidant, antibacterial, anti-TB, antimalarial, antiviral, anti-HIV, and many other uses. Variously substituted quinoxalines are significant therapeutic agents in the pharmaceutical industry. This review spotlights on the chemistry, physiochemical characters, synthesis, pharmaceutical products, and medicinal chemistry of various anticancer quinoxaline derivatives that were developed in the last period. It covers the period from 2016 to 2023.

Synthesis of Antifungal Heterocycle-Containing Mannich Bases: A Comprehensive Review

Mannich bases are a class of organic compounds usually obtained by the condensation reaction between an amine, a compound with active hydrogens, and an aldehyde. They are versatile intermediates in organic synthesis, and those compounds containing this motif find applications in pharmaceutical, agrochemical, and even material fields since they are widely known for their wide range of biological activities, including antimicrobial properties. Thus, as part of our interest in antifungal agents, this narrative review aimed to gather information from the literature on the synthesis of various representative Mannich-base-containing compounds, particularly centered on those exhibiting antifungal properties. In this context, the compilation indicated that Mannich bases could be considered as a relevant toxophore/pharmacophore by incorporating heterocyclic moieties to be implemented for the design of new antifungal agents, given its proven efficacy against phytopathogens, other opportunistic human pathogens, and some dermatophytic fungal species, which can be further exploited as agrochemical agents or in medicinal applications to treat fungal infections. The antifungal effect exhibited by Mannich bases conjugated with oxa and/or aza-heterocycles suggests that compounds that have a heterocyclic system attached to the β-amino core are attractive alternatives oriented to the synthesis of novel and helpful antifungal agents.

Resolution of Expanded Porphyrinoids: A Path to Persistent Chirality and Appealing Chiroptical Properties.

Chirality is a fundamental characteristic of nature. Expanded porphyrinoids and their analogues offer an attractive platform for delving into the intricacies of chirality. Expanded porphyrinoids comprise pyrrolic macrocycles and related heterocyclic systems. As a class, expanded porphyrinoids are widely recognized for their flexible structural features, nontrivial coordination capabilities, and intriguing optical and electronic properties. With limited exceptions, their inherent conformational flexibility coupled with a low racemization barrier allows for the facile interchange between enantiomers. As a result, achieving the effective chiral resolution of individual enantiomers and the subsequent exploration of their chiroptical properties represents a significant challenge. This review summarizes strategies used to realize the chiral resolution of expanded porphyrinoids and the understanding of intrinsic chiroptical properties that has emerged from these separation efforts. It is our hope that this review will serve not only to codify our current understanding of chiral expanded porphyrinoids, but also inspire advances in the generalized area of chiral functional materials.

Activated cyanoacetamide in heterocyclic synthesis: Design, synthesis, antitumor activity and docking study of some new pyrimidine derivatives

The precursor cyanoacetamide derivatives (6) were achieved by the reaction of pyrimidine derivative 5 with cyanoacetic acid catalyzed by acetic anhydride. The reaction of cyanoacetamide derivative 6 with different reagents afforded many heterocyclic systems such as thioacetic acid (9), dithiolane derivatives (11) and (12), 1,8-naphthyridine (14), quinoline derivatives (17) and (18), pyridine derivatives 20, 22, 24, 26, and 27, pyridazine (30), pyranopyrimidine (32), and pyrazolopyrimidine (34). All the newly synthesized compounds were characterized with spectroscopic analyses. Compounds were tested for their anticancer activity against three human cancer cell lines: hepatocellular carcinoma (HepG-2), colon cancer (HCT-116), and mammary gland breast cancer (MCF-7). The studied compound's cytotoxic activity ranged from very strong to very weak. The most active compounds were 9, 10, 11, 27, and 34. The binding disposition of the docked compounds, in particular 9, 10, 11, 27, and 34, towards the binding site of AKT complexed with co-crystallized ligand was investigated using molecular docking (PDB = 4EJN).

PKas of Five Membered Heterocyclic Ring Systems C4H4XH (X = N, P, As, Sb, Bi, Mc) Including the Novel Hypothetical Molecule Moscole (C4H4McH)

pKas of Five Membered Heterocyclic Ring Systems C4H4XH (X = N, P, As, Sb, Bi, Mc) Including the Novel Hypothetical Molecule Moscole (C4H4McH)

Synthesis of new polynuclear heterocyclic systems based on 7,8-diamino-5-nitroquinoline

Synthesis of new polynuclear heterocyclic systems based on 7,8-diamino-5-nitroquinoline

Ring Expansion Reactions through Intramolecular Transamidation

AbstractSynthetic methodologies based on cycle expansion reactions have proven to be highly effective in delivering valuable medium‐sized cycles and macrocycles. A primary method of ring expansion relies on intramolecular transamidation reactions. These reactions typically employ N‐aminoalkyl and N‐aminoacyl derivatives of lactams and their analogues as starting materials, yielding a diverse spectrum of unique nitrogen‐containing heterocycles.This Review aims to provide a comprehensive analysis of the research outcomes related to intramolecular transamidation reactions that lead to cycle expansion. This will offer the reader a perspective on the potential applications of such reactions in generating novel and intriguing types of heterocyclic systems.

Straightforward Approach to 5-Substituted 7H-Imidazo[2,1-b] [1,3]thiazines via Cyclization of 2-Alkynylthioimidazoles

AbstractElectrophile-initiated nucleophilic cyclization of 2-alkynylthiobenzimidazoles is a useful tool for synthesizing new heterocyclic systems. However, halogen-initiated cyclization demonstrates poor selectivity between electrophilic addition and substitution reactions using other imidazole analogues. In this research, several different coinage metal catalysts were employed to broaden the scope of 7H-imidazo[2,1-b][1,3]thiazines in atom-economic manner. Selective 6-endo-dig pathway reactions were achieved in good to excellent yields using various 2-alkynylthioimidazoles with AuCl as the catalyst in DCE/DCM.

Synthesis and Characterization of Some New Pyridine-Carboxamide Derivatives of Potential Biological Activities

A facile synthetic routes to access some new heterocyclic systems containing potent pharmacophoric groups such as pyrazole, pyrazolo[5,1-c]-1,2,4-triazine, 1,2,4-triazino[4,3-a]benzimidazole, and pyridine moieties linked to pyridine-carboxamide moiety are reported. Construction of the target compounds was achieved via reaction of 3-oxo-butanamides 1a,b with hydrazonoyl halides, heterocyclic diazonium salts, and malononitrile derivatives, respectively. The structures of the new products were confirmed by all possible spectral and elemental analyses. The antibacterial assessment showed that one product was moderately active against both K. pneumonia and S. aureus.

Computational and experimental analysis of catalyst-free and expeditious synthesis of Benzo[4,5]imidazo[2,1-b]thiazole derivatives

A greener and direct approach to the efficient synthesis of fused heterocyclic ring system benzo[4,5]imidazo[2,1-b]thiazoles via C–N and C–S bond formation in catalyst-free conditions has been reported using 2,2,2-trifluoroethanol (TFE) as a reaction medium at room temperature. The salient features of this approach include an elementary and clean reaction protocol to afford the desired product in higher yields in less reaction time with sufficient purity. This prominent moiety is frequently found in many natural bioactive occurring compounds and shows potential in synthesizing diverse biologically active compounds due to their therapeutic values. The synthesis of benzo[4,5]imidazo[2,1-b]thiazoles was confirmed by spectral analysis and also by DFT studies.

Unexpected efficient one-pot synthesis, DFT calculations, and docking study of new 4-hydroxy-2H-chromen-2-one derivatives predicted to target SARS-CoV-2 spike protein

A series of new heterocyclic systems derivatives of coumarin were prepared, and their chemical structures were well confirmed by 1H/13C NMR analyses. On the other hand, Spike-RDB protein of SARS-CoV-2 virus is one of the most crucial investigated targets in the field of combat against Covid-19 pandemic, due to its decisive role in the infection process by facilitating viral entry into the human host cells. In this context, Molecular docking experiments were carried out to identify the possible binding affinity of the synthesized compounds in the binding domain of Omicron S-RBD–hACE2 complex. The outputs revealed that some compounds showed highest binding affinities even than the control drugs used in this study. It was found that certain crucial residues like Glu37, His34, and Lys353, responsible for the binding of the spike protein to its hACE2 receptor, established significant hydrogen and electrostatic interactions with the ligands.

One-Pot Access to Boron-Doped Fused Heterocycles via Domino Cyclization of Bis-Diazidoboranes with Isonitrile.

Boron-doped fused heterocycles have shown great potential in the field of functional materials. This study reports on the synthesis of a new class of bis-diazidoboranes and the discovery of their cycloaddition reaction with isonitriles. Triply fused boron-doped heterocyclic compounds were constructed in a one-pot process through a domino cycloaddition, providing an effective route for constructing complex boron-doped heterocyclic systems.

Nitrene Cyclization of 2-(Trichloromethyl)-5-phenylpyrimidines: Application to the Synthesis of 2-(Trichloromethyl)pyrimido[4,5-b]indoles and Related Heterocycles

AbstractAn aromatic C–H nitrene insertion of 2-(trichloromethyl)pyrimidines bearing a phenyl substituent at the C-5 position is described. Treatment of 4-chloro-5-phenyl-2-(trichloromethyl)pyrimidines with sodium azide in DMF or the reflux of 4-azido-5-phenyl-2-(trichloromethyl)pyrimidines in toluene provided 2-(trichloromethyl)pyrimido[4,5-b]indole derivatives in moderate yields. Excellent yields of this heterocyclic system were obtained through the aromatic C–H insertion with the Du Bois catalyst. This is an attractive approach for synthesizing pyrimido[4,5-b]indoles with a trichloromethyl substituent in the pyrimidine moiety.

Recent Developments in the Transformation of 3-amino-2-azetidinones

Abstract: Functionalized 3-amino-2-azetidinones are important heterocyclic systems which can easily be transformed into functionally decorated heterocycles using β-lactam synthon protocol. The different synthetic methods have been explored for the transformation of functionalized 3-amino-2-azetidiones to various heterocyclic molecules, such as imidazolidin-2-ones, piperazines, hydantoins, 4-oxo-1H-pyrroles, 1,4-benzodiazepin-2-ones, amino pyrrolidine-2- carboxylates etc., and β-lactam- based conjugates having diverse biological activities, such as anti-malarial activity, anti-tuberculosis, anti-trichomonas activity etc. The present review article summarizes the various reports on the synthetic transformation of functionalized 3-amino-2- azetidinones for the synthesis of a variety of heterocyclic systems.

Pyrazole and Benzimidazole Derivatives: Chelating Properties Towards Metals Ions and their Applications

Abstract: Due mainly to their structural diversities, pharmacological, electrochemical, and photophysical properties, the metal synthesis pyrazole and benzimidazole complexes were extensively designed and developed. The nitrogen-containing ligands playing an important role in coordination chemistry contain a wide variety of heterocyclic systems possessing one or more nitrogen atoms as electron donors, such as pyridine, isoxazole, pyrazole, 1,2,4-triazole, 1,3,5-triazine, quinoline, quinoxaline and benzothiazole. The structure of all ligands and the corresponding metal complexes are established using elemental analysis, infrared spectroscopy, NMR spectroscopy, mass spectrometry, single-crystal X-ray diffraction, thermogravimetric differential thermal analysis, static, magnetic susceptibility measurements, electron paramagnetic resonance spectroscopy (EPR), UV-Vis spectroscopy, and conductivity measurements.In this review, we report the synthesis and the chelating reactions of several heterocyclic ligands with various metals such as transition metals and lanthanides. The photophysical and photochemical properties of the metal complexes will also be presented and discussed.

Benzimidazole: A versatile scaffold for drug discovery and beyond – A comprehensive review of synthetic approaches and recent advancements in medicinal chemistry

Heterocyclic compounds are foundational in drug discovery, constituting the core structure of approximately 80% of pharmaceuticals. Benzimidazole, in particular, emerges as a critical aromatic heterocyclic system present in natural compounds, playing an indispensable role in medicinal chemistry. Beyond its pharmaceutical importance, benzimidazole demonstrates its versatility across diverse domains, including materials science and a wide spectrum of pharmacological applications, encompassing antiviral, antifungal, antioxidant, and anticancer properties. The prominence of benzimidazole in both biological activities and industrial applications underscores its pivotal role as a versatile heterocyclic scaffold. Its outstanding attributes, such as enhanced bioavailability, stability, and biological activity, have drawn significant attention from both researchers and industries. This comprehensive review delves into various synthetic approaches to benzimidazole synthesis, with a focus on practical and eco-friendly pathways utilizing various catalysts, including biocatalysts, nanocatalysts, and photocatalysts. Additionally, this review sheds light on the recent advancements of benzimidazole across multiple sectors, spanning pharmaceuticals, materials science, agriculture, and coordination chemistry. Finally, this work summarized the major challenges and presents potential directions for future research endeavors in benzimidazole applications within pharmaceuticals, agriculture, and industrial sectors.