N-heterocyclic Derivatives Research Articles

Radical Cascade Cyclization of N-(o-Cyanobiaryl)acrylamides with Sulfonium Salts via Synergetic Photoredox and Copper Catalysis.

As the magic methyl effect is well acknowledged in pharmaceutical molecules, the development of simple and efficient methods for the installment of methyl groups on complex molecules is highly coveted. Hence, we provide a general strategy for radical cascade cyclization of N-(o-cyanobiaryl)acrylamides by utilizing sulfonium salts as the sources of methyl radical and merging photoredox and copper catalysis. This novel protocol can access a wide variety of methylation or remote thioether-substituted benzo-fused N-heterocycle derivatives, which can be easily transformed into diverse highly valuable sulfone and sulfoximine compounds via late-stage diversification. Moreover, to further demonstrate the synthetic utility of this conversion, the methyl(phenyl)sulfide, which serves as both raw material and byproduct, can be recovered and reused in this transformation. The scale-up experiment for the one-pot two-step process directly offers the target product in good yield under the standard conditions.

Synthesis, Evaluation and Docking Studies of Disubstituted N-Heterocyclic Derivatives as Anticancer Agents.

Cancer is a chronic disease reported with alarming rates of mortalities every year. Herein, we reported the synthesis of nitrogen based novel heterocyclic disubstituted derivatives and evaluated them against L929 and A549 cell lines using MTT assay. Among all, 6a2 and 6c1 were significantly active against L929 with IC50 value of 2.61±9.58 and 2.64±8.97 µg/mL respectively. Compounds 6a2 and 6c1 were also active against A549 with IC50 value of 2.36±9.20 and 2.43±6.28 µg/mL respectively and were found to be more potent than the standard drug Doxorubicin. A molecular docking study of the active compounds was also done against EGFR, conferring good binding affinity and binding interactions. Further biological investigations may provide valuable insights towards exploring the therapeutic potential of the active compounds in future.

Mechanical milling promotes the preparation of catalyst lanthanum dodecyl sulfate and green solvent-free grinding for synthesis of N-heterocyclic derivatives

The lanthanum dodecyl sulfate catalyst (La(DS)3) was synthesized using a solvent-free mechanical ball method and applied in the preparation of solvent-free N-heterocyclic compounds. The preparation of the La(DS)3 catalyst and the synthesis of C-N bond series compounds only require brief ball milling of the mixed material at room temperature. Various analyses such as SEM, HRTEM, XRD, AFM, FT-IR, XPS, TGA, and DFT were conducted, which showed that the catalyst material synthesized by mechanical ball milling exhibited superior catalytic activity, thermal stability, and cyclic life compared to similar materials synthesized in an aqueous phase. The solvent-free catalytic synthesis of quinoxaline, dihydroacridin-1(2H)-one, and bis(indolyl)methanes derivatives achieved excellent target yields. Furthermore, the catalyst could be reused at least seven times without a significant decrease in activity after simple treatment. The catalyst also demonstrated gram scale scaling up in the model reaction. It exhibited weak hydrophilicity and a stable network-like layered nanostructure.

Mild and Efficient Preparation of N-Heterocyclic Organic Molecules by Catalyst-free and Solvent-free Methods.

The small organic molecular compounds with biological activity containing C-C and C-N or C-O bonding were efficiently prepared without catalyst and solvent in the hydrothermal synthesis reactor. Our goal was to explore new applications for the more environmentally friendly and efficient synthesis of bis(indolyl)methyl, xanthene, quinazolinone, and N-heterocyclic derivatives in hydrothermal synthesis reactors under solvent-free and catalyst-free conditions. A greener and more efficient method was successfully developed for the synthesis of bis(indolyl)methyl, heteroanthracene, quinazolinone, and N-heterocyclic derivatives using a hydrothermal synthesis reactor in a solvent- and catalyst-free manner. In a hydrothermal synthesis reactor, bis(indoyl)methyl, xanthene, quinazolinone, and N-heterocyclic derivatives were synthesized without catalysts and solvents. Overall, it is proved once again that the catalyst-free and solvent-free synthesis method has universal value and is a more ideal and environmentally friendly new method, especially the hydrothermal reactor for synthesis.

2,5-diphenyloxazole and 4-pyrrolidinopyridine as conformers to picric acid: Structural characterization coupled with Multivariate Statistical Analysis

In this study, 4-pyrrolidinopyridine (PPY) and 2,5-diphenyloxazole (DPO) were employed as N-heterocyclic derivatives to synthesize novel picrate salts. These salts were subsequently subjected to characterization using infrared spectroscopy, ultraviolet spectroscopy, and single-crystal X-ray diffraction. Comparison of these structures with entries in the Cambridge Structural Database (CSD) and the application of two multivariate statistical analyses, namely Principal Component Analysis (PCA) and Hierarchical Cluster Analysis (HCA), facilitated the differentiation of salts and co-crystals based on the structural behaviors of the picrate molecule. Additionally, Hirshfield Surface Analysis and 2D fingerprint plots were employed to investigate intermolecular contacts. The fluorescence emission spectra revealed that compound 2 has the potential to serve as a probe for turn-off detection of picric acid (PA).

Photoactive benzothiadiazole-N-heterocycle derivatives: synthesis, photophysics and water sensing in organic solvents

The study reported herein describes the synthesis of benzothiadiazole (BTD)-N-heterocycle derivatives by metal-catalyzed cross-coupling reactions with relatively good yields.

Design, synthesis and neuroprotective evaluation of nitrogen heterocyclic and triazole derivatives of sarracinic acid

Novel sarracinic acid derivatives bearing triazole or N-heterocyclic moiety were prepared via two separate reaction schemes. The triazoles and the N-heterocyclic derivatives were synthesised using standard click chemistry approach and amination of 2-bromoethyl ester of sarracinic acid respectively. All the synthesised derivatives were screened for in vitro neuroprotective activity against corticosterone induced impairment in neuroblastoma cell line SH-SY5Y. Two analogs SA-2 and SA-12 exhibited strong neuroprotective activity. The cell viability, after high dose corticosterone induced cell death, increased remarkably with the pre treatment of SA-2 and SA-12. The in vitro biological activity of SA-2 and SA-12 was verified through docking studies. The docking studies were in good agreement with the biological results. SA-2 and SA-12 showed strong binding affinities with the target protein having ΔGb = −8.88 and −7.52; inhibition constant (ki) = 3.08 nM and 30.9 nM respectively.

Recent Advances in the Green Synthesis of Active N-Heterocycles and Their Biological Activities.

N-heterocyclic scaffolds represent a privileged architecture in the process of drug design and development. It has widespread occurrence in synthetic and natural products, either those that are established or progressing as potent drug candidates. Additionally, numerous novel N-heterocyclic analogues with remarkable physiological significance and extended pharmaceutical applications are escalating progressively. Hence, the classical synthetic protocols need to be improvised according to modern requirements for efficient and eco-friendly approaches. Numerous methodologies and technologies emerged to address the green and sustainable production of various pharmaceutically and medicinally important N-heterocyclic compounds in last few years. In this context, the current review unveils greener alternatives for direct access to categorically differentiated N-heterocyclic derivatives and its application in the establishment of biologically active potent molecules for drug design. The green and sustainable methods accentuated in this review includes microwave-assisted reactions, solvent-free approaches, heterogeneous catalysis, ultrasound reactions, and biocatalysis.

Design and synthesis of sinomenine D-ring tetrazole-isoxazole and tetrazole-triazole derivatives via 1, 3-dipolar cycloaddition reaction

The synthesis of D-ring tetrazole-isoxazole and tetrazole-triazole sinomenine derivatives at N–CH3via 1, 3-dipolar cycloaddition reactions were accomplished and a total of 34 novel sinomenine N-heterocyclic derivatives were obtained in 69–93% yields. The N–CH3 of sinomenine was first transformed into N–CN structure under the action of cyanogen bromide, and then N–CN reacted with sodium azide to give the N-tetrazole derivative. The N–H bond on tetrazole was replaced by different isoxazole bromides to get tetrazole-isoxazole sinomenine derivatives directly. The N–H bond on tetrazole was replaced by propargyl bromide to give sinomenine derivative with propargyl group, the terminal alkyne then reacted with the 1, 3-dipole in situ to obtain D-ring tetrazole-triazole sinomenine derivatives. All the synthesized derivatives are characterized by FT-IR, HRMS, 1H NMR, and 13C NMR spectroscopy.

N-Heterocycle derivatives: An update on the biological activity in correlation with computational predictions

N-Heterocycle derivatives: An update on the biological activity in correlation with computational predictions

New Histamine-Related Five-Membered N-Heterocycle Derivatives as Carbonic Anhydrase I Activators.

A series of histamine (HST)-related compounds were synthesized and tested for their activating properties on five physiologically relevant human Carbonic Anhydrase (hCA) isoforms (I, II, Va, VII and XIII). The imidazole ring of HST was replaced with different 5-membered heterocycles and the length of the aliphatic chain was varied. For the most interesting compounds some modifications on the terminal amino group were also performed. The most sensitive isoform to activation was hCA I (KA values in the low micromolar range), but surprisingly none of the new compounds displayed activity on hCA II. Some derivatives (1, 3a and 22) displayed an interesting selectivity for activating hCA I over hCA II, Va, VII and XIII.

N-Heterocyclic carbene derivatives to modify gold superatom characteristics. Tailorable electronic and optical properties of [Au11(PPh3)7LCl2]+ as a cluster from relativistic DFT.

Atomically precise gold superatoms are useful building blocks whose properties can be tuned by the proper choice of ligands in the protecting ligand layer. Herein, different N-heterocyclic carbene (NHC) derivatives of the prototypical [Au11(PPh3)8Cl2]+ cluster were evaluated by the replacement of a single ligand, which led to isoelectronic [Au11(PPh3)7(NHC)Cl2]+ species, enabling further understanding of the possible changes in the resulting cluster properties. Our results reveal the great variation in the HOMO-LUMO gap and optical features when going from strong to weak σ-donor NHC ligands. The Au11 core retains similar features throughout the series, and the lowest unoccupied orbital (LUMO) is further stabilized, indicating greater π*-NHC character for the weaker σ-donor ligands, which favors directional core-ligand optical charge transfer to a single ligand. The ligand-tailored behavior of the [Au11(PPh3)7LCl2]+ cluster underlies its tunable characteristics, indicating its potential use in novel devices as building blocks of nanostructured materials, which favors further versatility and applications of superatomic clusters.

Two Hybrid Polymeric Iodoargentates Incorporating Aromatic N-Heterocycle Derivatives as Electron Acceptors.

Two new hybrid polymeric iodoargentates, [Ag2I2(phen)]n (1; phen = 1,10-phenanthroline) and [AgI(bpt)]n (2; bpt = 3,5-bis(pyrazinyl)-1,2,4-triazole), were prepared by the hydrothermal methods. 1 displays a new type of taenioid, [Ag2I2(phen)]n, chain incorporating phen molecules, while 2 exhibits a unique 2D hybrid iodoargentate based on a combination of the [AgI]n layer and bpt molecules as electron acceptors. Such a 2D layer is the first example of an inorganic iodoargentate layer covalently bonding to aromatic N-heterocycle derivatives within the iodoargentates. 1 and 2 exhibit photocurrent response properties.

Design and synthesis of C-ring quinoxaline-substituted sinomenine 1,2,3-triazole derivatives via click reactions

The synthesis of C-ring quinoxaline-substituted sinomenine 1,2,3-triazole derivatives at the 4-OH via click reactions is accomplished, and a total of 16 novel sinomenine double N-heterocyclic derivatives are obtained in 74%–95% yields. The C-ring is first transformed into a 1,2-diketone structure under the action of hydrochloric acid, and then reacted with o-phenylenediamine to obtain a C-ring quinoxaline-substituted structure. The 4-OH of sinomenine reacts with chloropropyne to give an alkynyl sinomenine, and then reacts with sodium azide and various benzyl chlorides to give the target compounds. All the synthesized derivatives are characterized by Fourier-transform infrared spectrometry, high resolution mass spectrometry, 1H NMR, and 13C NMR spectroscopy.

Synthesis and photophysical insights of new fused N-heterocyclic derivatives with isoquinoline skeleton

Six new fused isoquinoline based compounds (compounds 5a–c with pyrrolo[2,1-a] isoquinoline structure and compounds 6a–c with imidazo[2,1-a]isoquinoline skeleton) have been synthesized using the [3 + 2] cycloaddition of the several in situ generated cycloimmonium ylides to ethyl propiolate or ethyl cyanoformate. All the synthesized compounds have been investigated in solution by UV–VIS absorption, steady and time-resolved fluorescence methods. The effect of the substituents on the spectral characteristics has been demonstrated. These derivatives displayed an intense emission between 360 and 420 nm. The emission quantum yields (Φ = 0.54–0.64) of pyrroloisoquinoline derivatives in dimethylsulfoxide (DMSO) were significantly higher than those of imidazoquinolines (0.03–0.16). The fluorescence decay of isoquinoline derivatives follows a biexponential law. A noticeable response of these isoquinoline derivatives to sodium hydroxide was observed.

Novel Cu(II), Ni(II), Zn(II), Cd(II), and Mg(II) complexes with a series of 2-arylhydrazono-1,3-dicarbonyl compounds. Synthesis, structure and spectroscopic characteristics

A series of novel metal complexes of Cu(II), Ni(II), Zn(II), Cd(II), and Mg(II) with four N-heterocyclic derivatives of 2-arylhydrazono-1,3-dicarbonyl compounds were isolated and identified by FT IR, 1H NMR, EPR, and UV–Vis spectroscopy. The crystallographic data for two organic ligands as well as Mg(II) and Ni(II) complexes were obtained. It was indicated that the organic species exist in the form of hydrazo-tautomers. The Ni complex is monomeric and is characterized by the tridentate coordination of the ligand through a deprotonated N-atom of the hydrazo-fragment and two neighboring O-atoms of the carbonyl and deprotonated hydroxy-groups. In the case of the Mg complex the polymeric structure is observed with the additional coordination through the sulfamide group of the organic specie. Formation constants of the complexes in ethanol aqueous solutions were calculated and correlated with some physical characteristics of the metal cations. Structures of yet unstudied metal complexes were proposed based on quantum-chemical modeling at the DFT/B3LYP level.

AuCl3 -Catalyzed Ring-Closing Carbonyl-Olefin Metathesis.

Compared with the ripeness of olefin metathesis, exploration of the construction of carbon-carbon double bonds through the catalytic carbonyl-olefin metathesis reaction remains stagnant and has received scant attention. Herein, a highly efficient AuCl3 -catalyzed intramolecular ring-closing carbonyl-olefin metathesis reaction is described. This method features easily accessible starting materials, simple operation, good functional-group tolerance and short reaction times, and provides the target cyclopentenes, polycycles, benzocarbocycles, and N-heterocycle derivatives in good to excellent yields.

Autophagy-regulating N-heterocycles derivatives as potential anticancer agents.

As a double-edged sword, autophagy in cancer cells could either suppress or promote tumorigenesis. Nowadays, more and more natural compounds with autophagy-regulating activities exhibit therapeutic effects against various cancers. N-Heterocycle derivatives plays an important role for discovery new drugs. In this review, we summarize and classify 116 N-heterocycle derivatives with autophagy-regulating activities in the past decade into 12 classes according to structure characteristics. The structural features, bioactivities, mechanism and problems faced in this field are discussed and reported for the first time. Some of these even exhibited outstanding in vivo antitumor activities, including bisaminoquinoline (3), pancratistatin (8), 10-hydroxyevodiamine (18), lycorine (28), piperine (31) and iridium (III) complex (57), which are potential drug candidates for antitumor therapy.

Nitrogen-Containing Heterocyclic Derivatives of Maleopimaric Acid by Carboxyl Function and their Antioxidant Activity

New N-heterocyclic maleopimaric acid derivatives were prepared and shown to affect free-radical oxidation in model systems, in particular, to suppress reactive oxygen species generation and stimulated lipid peroxidation in model systems containing lipoproteins.

Palladium(0)-Catalyzed Diastereoselective (3+2) Cycloadditions of Vinylcyclopropanes with Sulfonyl-Activated Imines

We report herein a palladium(0)-catalyzed (3+2)-cycloaddition process between vinylcyclopropanes and cyclic or acyclic sulfonylimines. This reaction, which operates under low catalyst loading and practical reaction conditions, gives access to a wide variety of N-heterocyclic derivatives in good to excellent yields and high levels of diastereoselectivity.