Synthesis Of Pyrazole Derivatives Research Articles

Current Advances in Synthesis of Pyrazole Derivatives: An Approach Toward Energetic Materials

Current Advances in Synthesis of Pyrazole Derivatives: An Approach Toward Energetic Materials

Magnetic Nanoparticles‐Supported Synthesis of Pyrazole Scaffolds: A Review

AbstractIn the present era, the concept of green in organic synthesis has a unique and irreplaceable place. Specifically, nanoparticle has gained much more attention due to its various properties related to the concept of green chemistry. In this context, magnetic nanoparticle has been widely used in the organic synthesis over last one decade. Among organic compounds, pyrazole and its scaffolds are recognized as a privileged structure as it represents a promising area for identification of lead structures towards the discovery of new synthetic drug molecules and other valuable candidates. Several commercial drugs such as Sildenafil, Rimonabant, Celecoxib and many other compounds in biological testing and preclinical evaluation, illustrate the wide therapeutic spectrum in this class of drug scaffolds. Accordingly, the magnetic nanoparticles have an irreplaceable place in the synthesis of pyrazole derivatives and it is a green and easy methodology to the organic chemists. The present manuscript represents the assimilation of literature pertaining to green aspects of magnetic nanoparticles for the synthesis of highly diversified and valuable derivatives of pyrazole.

Design and synthesis of pyrazole derivatives against neutrophilic inflammation

Neutrophils are the most abundant immune cells. However, neutrophil dysregulation leads to acute and chronic inflammation and is involved in various diseases. The aim of this study was to develop anti-inflammatory agents in human neutrophils. A drug screening was conducted on in-house compounds with the potential to inhibit the respiratory burst, which involves the generation of superoxide anions in human neutrophils. Bioisosteric replacement was then applied to design more active derivatives. The most potent inhibitors of superoxide anion generation activity were compounds 58 and 59, which had IC50 values of 13.30 and 9.06 nM, respectively. The inhibitory effects of 58 and 59 were reversed by H89, a PKA inhibitor. PDE selective screening indicated that the best inhibitory effects were PDE4B1 and PDE4D2, and the inhibitory activities were 83% and 85%, respectively, at a 10 μM concentration of 59. The final molecular simulation experiment highlighted the slightly different binding poses of 58 and 59 in the PDE4 active site. An in vivo pharmacokinetic study revealed that the half-life of 59 was approximately 79 min when using intravenous bolus administration. This work introduced a new class structure of PDE4 inhibitors resulting in potent neutrophil inactivation activity, with the aim of contributing to new anti-inflammatory drug discovery.

Synthesis of New Zirconium Magnetic Nanocomposite as a Bioactive Agent and Green Catalyst in the Four-Component Synthesis of a Novel Multi-Ring Compound Containing Pyrazole Derivatives.

New nanocomposites containing zirconium were synthesized using microwave irradiation. Their structure was confirmed by vibrating sample magnetometer (VSM) curves, X-ray diffraction (XRD) patterns, scanning electron microscope (SEM) and transmission electron microscopy (TEM) images, Fourier transform infrared spectroscopy (FT-IR), and Brunauer-Emmett-Teller (BET) N2 adsorption/desorption isotherms. After the structure confirmation of the zirconium magnetic nanocomposite, the catalytic properties in the synthesis of pyrazole derivatives were investigated. Next, the biological activities of the zirconium magnetic nanocomposite, such as the antibacterial and antifungal activities, were investigated. The research results showed that the zirconium magnetic nanocomposite has high catalytic properties and can be used as a magnetic nanocatalyst for synthesizing heterocyclic compounds such as pyrazole derivatives in addition to having high biological properties. The unique properties of the nanoparticles can be attributed to their synthesis method and microwave radiation.

Pyrazole Derivatives As Potent EGFR Inhibitors: synthesis, Biological Evaluation and In Silico and Biodistribution Study

Aim: Synthesis of pyrazole derivatives as EGFR inhibitors. Materials & methods: Cytotoxicity and EGFR inhibitory effect were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and EGFR kits, respectively. The biodistribution of radioiodinated compound nanoparticles in tumor-bearing mice was studied. Results: The IC50 values of compound 4a against HepG2 cells and EGFR were 0.15±0.03 and 0.31±0.008μM, respectively, while those of erlotinib were 0.73±0.04 and 0.11±0.008μM, respectively. The binding scores of compound 4a and erlotinib to EGFR were -9.52 and -10.23 Kcal/mol, respectively. The maximum tumor uptake of radioiodinated compound after intravenous nanoparticle injection was 6.7±0.3% radioactivity/g. Conclusion: Compound 4a is a promising antitumor agent with a potential EGFR inhibitory effect.

Recent Applications of the Multicomponent Synthesis for Bioactive Pyrazole Derivatives.

Pyrazole and its derivatives are considered a privileged N-heterocycle with immense therapeutic potential. Over the last few decades, the pot, atom, and step economy (PASE) synthesis of pyrazole derivatives by multicomponent reactions (MCRs) has gained increasing popularity in pharmaceutical and medicinal chemistry. The present review summarizes the recent developments of multicomponent reactions for the synthesis of biologically active molecules containing the pyrazole moiety. Particularly, it covers the articles published from 2015 to date related to antibacterial, anticancer, antifungal, antioxidant, α-glucosidase and α-amylase inhibitory, anti-inflammatory, antimycobacterial, antimalarial, and miscellaneous activities of pyrazole derivatives obtained exclusively via an MCR. The reported analytical and activity data, plausible synthetic mechanisms, and molecular docking simulations are organized in concise tables, schemes, and figures to facilitate comparison and underscore the key points of this review. We hope that this review will be helpful in the quest for developing more biologically active molecules and marketed drugs containing the pyrazole moiety.

Core‐shell structured magnetite silica‐supported hexatungstate: A novel and powerful nanocatalyst for the synthesis of biologically active pyrazole derivatives

AbstractThis article describes the synthesis of a novel core‐shell structured magnetic silica‐supported hexatungstate (Fe3O4@SiO2‐NH3[W6O19]) nanocatalyst through immobilization of hexatungstate on amine‐modified magnetic silica nanoparticles. The physicochemical properties of Fe3O4@SiO2‐NH3[W6O19] were investigated by using Fourier transform infrared (FT‐IR) spectroscopy, powder X‐ray diffraction, vibrating sample magnetometer, wide‐angle PXRD, scanning electron microscopy, transmission electron microscopy, and energy‐dispersive X‐ray spectroscopy analyses. The Fe3O4@SiO2‐NH3[W6O19] nanocatalyst was used as a powerful and heterogeneous catalyst in the synthesis of pyrazole derivatives. This novel catalyst was reused at least seven times without loss of its activity.

Recent Advances in Synthesis of Pyrazole Derivatives using Functionalized Catalysts Immobilized on Silica

AbstractThe pyrazole moiety is found as an integral structural unit in a variety of pharmacologically and agrochemically significant chemicals. The anti‐inflammatory (celecoxib), anti‐obesity (rimonabant), analgesic (difenamizole), antipsychotic (CDPPB), H2‐receptor agonist (betazole), and antidepressant (fezolamide) activities of pyrazole‐based drugs have demonstrated their pharmacological importance. Various synthetic methodologies have been devised as a result of the above‐mentioned advantages of pyrazole‐based compounds, including solvent‐free approach, catalyst‐free method, homogeneous catalysis, heterogeneous catalysis, microwave irradiation technique, ultrasonication, etc. In the area of heterogeneous catalysis, silica functionalized catalysts have garnered a lot of interest among diverse heterogeneous catalysts. The significant advancements in silica functionalized heterogeneous catalysts for the production of pyrazole‐based compounds are highlighted in this review.

Recent Advances in the Synthesis of Pyrazole Derivatives

Recent Advances in the Synthesis of Pyrazole Derivatives

Recent Advances in the Synthesis of Pyrazole Derivatives.

Pyrazole and its derivatives have gained wide attention in pharmaceutical, agrochemical and biological fields as well as in industry. They exhibit various biological activities such as anti-pyretic, anti-microbial, anti- inflammatory, anti-tumor, anti-viral, anti-histaminic, anti-convulsant, fungicidal, insecticidal, etc. In this review, we summarise the recent advances in the synthesis of pyrazole derivatives using various methodologies and covers literature from 2017-2020.

Synthetic Methods and Antimicrobial Perspective of Pyrazole Derivatives: An Insight

Background: Due to newly emerging microbial infections and the development of resistance against cutting-edge therapeutics, innovative and robust medicinal agents are required. Small ring heterocycles, such as pyrazole and its derivatives have been acknowledged to possess myriad biological properties and the presence of pyrazole in clinics like celecoxib, phenylbutazone (anti-inflammatory), CDPPB (antipsychotic), rimonabant (anti-obesity), antipyrine, difenamizole (analgesic), fipronil (broad-spectrum insecticidal), betazole (H2-receptor agonist) and fezolamide (antidepressant) drugs has proven the pharmacological perspective of pyrazole nucleus. Objectives: The current review paper aimed at a recent update made on novel methodologies adopted in the synthesis of pyrazole derivatives with the emphasis on antibacterial (DNA gyrase inhibition) and antifungal activities. Methods: Pyrazole is one of the major tools to be investigated in drug design and discovery. Many studies have been reported by researchers that have claimed the significant biological potential of these derivatives. However, numerous studies on pyrazoles compounds shown to exhibit potential antifungal and antibacterial activities, the focus has also been made on DNA gyrase inhibition. Additionally, some important patents granted to this heterocyclic nucleus related to antimicrobial potential are also addressed appropriately. Results: DNA gyrase is a promising biotarget yet to be explored against a number of medicinal agents. The present work provides valuable insight into synthetic methods and antibacterials/antifungal significance of pyrazoles in general as well as new inhibitors of DNA gyrase in particular. Conclusion: The manuscript constitutes a valuable reference which advocates candidature of pyrazoles as a potential therapeutic alternative as antibacterial and antifungal agent.

Synergy of Deep Eutectics and Magnetite in NanoFe3O4@Choline Chloride: 2Urea as a New Reusable Catalyst for Synthesis of Pyrazoles

Background: Supporting of choline chloride (CC):2urea as a deep eutectic solvent (DES) on nonomagnetite gives the core-shell of nanoFe3O4@CC:2urea which in DES coating inhibits the agglomeration of nanoFe3O4 and nanoFe3O4 facilitates reusability of DES. The ratio of nanoFe3O4 to DES in nanoFe3O4@CC:2urea was determined as 8:1. These synergic effects led to a high catalytic performance for nanoFe3O4@CC:2urea versus individual nanoFe3O4 or CC:2urea in synthesis of pyrazole derivatives by various synthetic strategies. Faster reactions with higher yields at room temperature occur with low loading of this recyclable hybrid catalyst. Method: NanoFe3O4 and DESs were prepared by co-precipitation of FeCl3.6H2O and FeCl2.4H2O with NH3 and heating the mixture of CC and hydrogen donors to a homogeneous liquid. Then, nanoFe3O4@CC:2urea was prepared by sonication of nanoFe3O4 and dissolved CC:2urea in methanol. After characterization by FT-IR, SEM, TEM, TGA, and VSM, the efficacy of nanoFe3O4@CC:2urea was examined in one-pot synthesis of pyrazoles and pyranopyrazoles. Results: NanoFe3O4@CC:2urea is a hybrid organic/inorganic catalyst which in DES coating inhibits the agglomeration of Fe3O4 nanoparticles and nanoFe3O4 improves the reusability of DES. These synergic effects deliver a high catalytic performance for nanoFe3O4@CC:2urea in synthesis of pyrazoles and pyranopyrazoles. Faster reactions with higher yields at room temperature occur with low loading of this magnetically separable and reusable catalyst. Conclusion: In summary, synergic effects of CC:2urea and nanomagnetite in nanoFe3O4@CC:2urea lead to a reusable catalyst with superior catalytic activity in room temperature three- or four- component synthesis of pyrazoles and pyranopyrazoles. This magnetically separable DES provides higher yields of products, faster reactions, and milder conditions compared to previous reported methods. Keywords: Deep eutectic, nanoFe3O4, immobilization, pyrazoles, multicomponent reactions, synergic effect.

Recent Advances in the Synthesis of Pyrazole Derivatives Using Multicomponent Reactions

Recent Advances in the Synthesis of Pyrazole Derivatives Using Multicomponent Reactions

Visible-light-photoredox catalytic C[sbnd]C, C[sbnd]N bond formation: Synthesis of pyrazole derivatives via radical ions

A new approach for 5-amino-pyrazole-4-carbonitriles has been developed employing visible light photoredox catalysis. The green attributes of our work exploit on the utilization of visible light and Eosin Y organo photocatalyst as inexpensive, non-toxic, readily-available and eco-compatible reagents. In this strategy atmospheric O2 served as an. economical and eco sustainable desulfurizing agent, efficiently promotes the formation of CC and CN bonds in a simple one-pot operation under mild conditions thus increase the efficiency of proposed protocol.

Urea/thiourea: efficient, inexpensive and reusable catalysts for the synthesis of pyrazole derivatives with 2-iminothiazolidin-4-one and 2,4-thiazolidinediones under solvent-free conditions.

Anefficientandgreensynthesisofpyrazolyl-2,4-thiazolidinediones/pyrazolyl-2-iminothiazolidine-4-ones 7(a-j) has been developed using urea/thiourea as catalyst. Two methods (A and B) have been introduced for the synthesis of these compounds. Method A performed well for the condensation of pyrazole-4-carboxaldehydes 4(a-e) with 2-iminothiazolidin-4-one 5a and with 2,4-thiazolidinedione 5b at 110 [Formula: see text] for 16-20minto furnish (Z)-5-((1,3-diphenyl-1H-pyrazol-4-yl)methylene)thiazolidine-2,4-diones 7(a-j) in excellent yields. In method B, the pyrazole-4-carboxaldehydes 4(a-e) were condensed with urea/thiourea at 110 [Formula: see text] for 10minto give key intermediates 6(a-j) which were later condensed with 5a and 5b to afford 7(a-j) via the elimination of urea/thiourea rather than the formation of a Biginelli product. These two protocols are inexpensive, eco-friendly and high yielding to provide the final products. The synthesis of compound 7f.

Relay Visible-Light Photoredox Catalysis: Synthesis of Pyrazole Derivatives via Formal [4 + 1] Annulation and Aromatization.

A relay visible-light photoredox catalysis strategy has been accomplished. Three successive photoredox cycles (one oxidative quenching cycle and two reductive quenching cycles) are engaged in a single reaction with one photocatalyst. This strategy enables formal [4 + 1] annulation of hydrazones with 2-bromo-1,3-dicarbonyl compounds, which functionalizes three C-H bonds of hydrazones. This method affords rapid access to a complex and biologically important pyrazole scaffold in a step-economical manner with high efficiency under mild conditions.

Synthesis of pyrazole derivatives in the presence of a dioxomolybdenum complex supported on silica-coated magnetite nanoparticles as an efficient and easily recyclable catalyst

A dioxomolybdenum complex supported on functionalized Fe3O4 magnetite nanoparticles as a heterogeneous catalyst was synthesized, characterized and used in the synthesis pyrazole derivatives.

An environmentally friendly electrochemical method for synthesis of pyrazole derivatives

Abstract Electrochemical oxidation of catechol and some of 3-substituted catechols (1a–c ) has been studied in the presence of 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one ( 3 ) as the nucleophile at various pH values in aqueous solution using cyclic voltammetric and controlled-potential coulometric methods. The results revealed that the products derived from catechols ( 1a–c ) participate in Michael addition reactions with 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one ( 3 ) via an ECEC mechanism, converts it to form the corresponding pyrazole derivatives ( 8a–c ). The electrosynthesis of these products was carried out at the surface of carbon electrode in an undivided cell under controlled-potential conditions which is an environmentally friendly method.

ChemInform Abstract: Efficient Synthesis of Fused Pyrazoles via Simple Cyclization of O‐Alkynylchalcones with Hydrazine.

Abstract The synthesis of pyrazole derivatives from o-alkynylchalcones and hydrazine via simple cyclization is described. This greener synthetic methodology provides a straightforward approach to the synthesis of a variety of pyrazole derivatives under mild reaction condition.

Efficient synthesis of fused pyrazoles via simple cyclization of o-alkynylchalcones with hydrazine

Abstract The synthesis of pyrazole derivatives from o-alkynylchalcones and hydrazine via simple cyclization is described. This greener synthetic methodology provides a straightforward approach to the synthesis of a variety of pyrazole derivatives under mild reaction condition.