Journal of Heterocyclic Chemistry最新文献

This review discusses the synthetic pathways of an important class of quinolines known as pyrimido[4,5-b]quinoline. Due to their profound range as biologically active compounds, they attracted the attention of medical/organic researchers. The construction of pyrimido[4,5-b]quinolines involved the intermolecular cyclization of diamino chloropyrimidine carbaldehyde and intramolecular cyclization of 2-amino-3-cyanotetra/hexahydroquinoline, 2-aminoquinoline-3-carbonitriles, ester or amide. That class of organic compounds was constructed from the reaction between 2-chloro-3-formylquinoline with amidine, urea, and thiourea. Also, barbituric acid and uracil and their analogous play an important role in synthesizing pyrimidoquinolines via multicomponent reaction strategies (MCR).

A series of novel cinnoline sulphonamide derivatives and 4-substuted cinnoline derivatives (13a-h, 16a-h and 17–31 total 33 analogues) were designed based on scaffold hopping techniques and evaluated for their antileukemic activity on wild type K562 as well as imatinib resistant cell lines (K562-IR1 and K562-IR2). Out of 33 analogues, five compounds (19, 22, 23, 28, and 31) exhibited potent antileukemic activity. An easy and efficient approach to synthesize numerous cinnoline derivatives by the various cross-coupling reactions of 4-chlorocinnoline has been developed and also demonstrated that metal-free cross couplings give high product yield compared with metal catalyzed cross couplings.

A simple and rapid synthesis of (S)-pyroglutamic acid was developed by the thermal cyclodehydration of (S)-glutamic acid under solvent-free conditions, with continuous swirling during heating (220°C) to ensure homogeneity of the melt. The reaction proceeds until the bubbles disappear, not exceeding 5 min. The heating immediately ceases, then cooling the reaction vessel to prevent degradation and racemization. (S)-pyroglutamic acid is obtained in 70% yield, and the enantiomeric ratio is 97:3. The same reaction under microwave heating in an aqueous solution afforded a low yield of racemic product.

A novel, catalyst-free photoinduced synthesis of 2,4-substituted quinazoline using 2-amino-aryl ketone, an aldehyde, and ammonium acetate was developed. A series of 2,4-substituted quinazoline compounds were obtained via irradiating the reactants with a light-emitting diode light (18 W) at room temperature. The broad substrate range and excellent gram-scale experimental results demonstrate the versatility of the reaction. To the best of our knowledge, the synthesis of 2,4-substituted quinazoline using ammonium acetate as the nitrogen source under photocatalysis has not been reported thus far. This method utilizes visible light oxidation to eliminate the use of oxidants in the reaction and is complementary to previous methods.

Several series of novel biheterocyclic compounds have been synthesized starting from 3-alkoxy-1H-pyrazole-4-carbaldehydes and employing different types of multicomponent reactions. The structures of the obtained 4-(pyrazol-4-yl)pyrano[2,3-c]pyrazole, 4-(pyrazol-4-yl)pyrazolo[4′,3′:5,6]pyrano[2,3-b]quinoline, 4-(pyrazol-4-yl)pyridine, and 4-[(pyrazol-4-yl)methylidene]-1,2-oxazole derivatives were thoroughly characterized and confirmed using detailed nuclear magnetic resonance spectroscopy (NMR), high-resolution mass spectrometry (HRMS), infrared spectroscopy (IR), and X-ray analysis.

N-Heterocyclic compounds have been appealing pharmacophores in their use as drug production substrates. In this review paper, the cyclization of N-heterocycles, using iron as a catalyst, and their mechanistic pathways have been highlighted and presented comprehensively. This paper will provide researchers with in-depth knowledge of their approach to synthesis by employing a greener way rather than a conventional one. The present review firmly establishes that iron catalysts by their innate ability and inherent potential to acquire the four oxidation states coupled with their easy accessibility, inexpensive, and environment-friendly nature have remained the mainstay in chemistry as the evergreen catalyst in the domain of organic synthesis. This review paper extensively explores iron-catalyzed cyclization of N-heterocycles, elucidating mechanistic pathways and emphasizing greener synthesis methods. Iron's versatility, accessibility, and eco-friendliness solidify its position as a cornerstone in organic synthesis.

Dienamine 2 was synthesized by reacting 5-aminopyrazole 1 with two moles of (DMF DMA). Enamine 2 underwent subsequent reactions with various reagents in different reaction media, leading to the formation of distinct compounds. In an acidic environment, enamine 2 reacted with acetyl acetone, benzoyl acetone, dimedone, and ethyl acetoacetate, resulting in the synthesis of compounds 9a, 9b, 13, and 17, respectively. Conversely, in a basic medium, dienamine 2 combined with malononitrile, ethyl cyanoacetate, and malononitrile dimer, yielding compounds 21a, 21b, and 25. Moreover, by reacting with ammonium acetate in acetic acid, dienamine 2 produced compounds 28. The synthesized compounds underwent in vitro testing against various bacterial and fungal strains, revealing significant antibacterial activity against hazardous bacterial strains. To identify potential bacterial targets, an in-silico study was initiated. Molecular docking investigations indicated that compound 25 exhibited the highest binding affinity toward dihydrofolate reductase and penicillin-binding proteins. Furthermore, compound 25 demonstrated robust physiochemical properties, bioavailability, and drug-like characteristics. These results collectively suggest the potential of compound 25 as a promising antibacterial agent with favorable drug properties.

Type 2 diabetes is a chronic disease characterized by insulin resistance and alterations in incretin secretion, such as the glucagon-like peptide-1 (GLP-1) hormone. GLP-1 plays a crucial role in signaling insulin production in the pancreas, with its activity regulated by the dipeptidyl peptidase 4 (DPP-4) enzyme. DPP-4 presents an intriguing strategy for controlling type 2 diabetes. This study focuses on synthesizing 22 novel oxadiazolone and pyrimidinone derivatives, in vitro DPP-4 inhibition, and elucidating binding modes through molecular docking simulations. Nine compounds showed promising inhibitory activity, with IC₅₀ values ranging from 0.3 to 1.86 mM. Molecular docking simulations revealed interactions between these compounds and critical residues in the enzyme's active site, such as Arg125, Glu206, Ser630, and His740. This investigation introduces a new class of DPP-4 inhibitors, providing insights into the design of more potent molecules as potential candidates for combating type 2 diabetes. The findings contribute to developing innovative therapeutics for managing this prevalent metabolic disorder.

A highly efficient, novel, two-phase liquid method using phase transfer catalyst is reported to prepare β-lactam-conjugated silver nanoparticles as an approach to improve antibacterial activity of β-lactams. In the method assisted by cetyltrimethylammonium bromide, NaBH₄ reduced AgNO₃ producing silver NPs that are coated with β-lactams. The studies conducted provide a generalized method applicable to all types of β-lactam substrates for capping on silver NPs. The NPs have been characterized by UV–Visible, Fourier transform infrared spectroscopy, x-ray diffraction, transmission electron microscopy, and dynamic light scattering methods.

Organic azides are universally important in many areas of chemistry, particularly in organic synthesis. The availability of these azides often depends on specific transfer reagents and reaction conditions, or only work with certain substrates. Customizable transfer reagents offer a safe and direct pathway to desired compounds, thereby increasing the availability of N-alkyl-azides. In an effort to streamline the synthesis and broaden the scope of N-azidoethyl-containing molecules, three different versatile azidoethyl transfer reagents were synthesized and a uniform reaction protocol with azoles as substrates, including imidazole, pyrazole, 1,2,3-triazole, 1,2,4-triazole, and tetrazole was established. The resulting azidoethyl-azoles were further used as ligands for energetic coordination compounds in an effort to create new lead-free primary explosives. A comprehensive characterization of the transfer reagents, the azidoethyl-containing products, and energetic coordination compounds was conducted using multinuclear nuclear magnetic resonance (NMR), elemental analysis, mass spectrometry, and infrared spectroscopy (IR). Furthermore, their thermal stability and sensitivity toward friction and impact were determined as well as the detonation properties were calculated by using the EXPLO5 code.