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Electrochemical transformations are considered a green alternative to classical redox chemistry as it eliminates the necessity for toxic and waste producing redox reagents. Typical electrochemical reactions require the addition of a supporting electrolyte – an ionic compound to facilitate reaction medium conductivity. However, this is often accompanied by an increase in the amount of produced waste. Here, we report an "in‐situ electrolyte" concept for facile, transition‐metal‐free, additive‐free one‐pot electrochemical preparation of isoxazol(in)es, important scaffolds for biologically active natural and synthetic molecules, from the respective aldehydes. The protocol utilizes no halogenated solvents and no external oxidants, while salt side‐products provide the ionic conductivity necessary for the electrosynthesis. The electrolysis is performed in an undivided cell, using the state‐of‐the‐art electrodes for the chlor‐alkali industry dimensionally stable and scalable mixed metal oxide anode and platinized titanium cathode of high durability. The cascade transformation comprises the condensation of aldehyde to oxime followed by its anodic oxidation and subsequent intra‐ and/or intermolecular [3+2] cycloadditions with an appropriate dipolarophile. Chemical yields up to 97 %, and good Faradaic efficiency, scalability, and stability are observed for most substrates in a broad scope. [ABSTRACT FROM AUTHOR]

Heterocyclic compounds, which are a privileged class of molecules with both natural and pharmacological value, plays an essential role in drug development. Research interest on heterocycles increasing rapidly due to the extensive pharmacological efficacy as more than 90% of novel drugs contain heterocycles. Nitrogen heterocyclic compounds, which are structural units of essential bioactive chemicals such as antibiotics, vitamins, hormones, etc, are more prevalent in nature than other types of heterocyclic ring systems. This analysis of the literature may provide a chance for chemists to develop innovative derivatives of heterocycles and their derivatives that have been demonstrated to be useful and safe agents in improving biological and industrial life quality. [ABSTRACT FROM AUTHOR]

Tethering of two biologically active molecules in a single unit is considered as a captivating solution for the extension of existing antibiotics. β-Lactams which display a vast array of biological properties due to various ring substitutions continue to attract the attention of synthetic chemists. The incorporation of the 'isoxazole' nucleus in its appendage is known to enhance the properties of β-lactam compounds. Its inclusion in the compounds offers decreased toxicity, increased efficacy, and improved pharmacokinetics spectrum. In the reported work, we highlight the efficient use of 1,3-dipolar cycloaddition reaction to synthesize novel isoxazole/dihydroisoxazole ring-linked β-lactam hybrids using 3-propargyloxy-β-lactams/3-allyl-β-lactams as synthons. The methodology devised has been found to be highly regioselective and generalized for the selected substrates to provide a variety of novel hybrid compounds under elementary reaction conditions. The synthesized compounds have been well characterized by various spectroscopic techniques and optimized reaction conditions for both types of hybrid compounds have been studied. [ABSTRACT FROM AUTHOR]

Synthesis, characterization, and theoretical studies of a novel limonene-bis(isoxazole)-thiazolidinone hybrid, prepared from natural D-limonene in five steps, were conducted. The compounds obtained were successfully identified using HRMS, 1H- and 13C-NMR spectral data. Subsequently, in-silico docking and molecular dynamic simulation studies were performed to predict potential interaction modes between the compounds and the active sites of the target hTopo IIα. Both studies indicated that all molecules exhibited good binding affinity towards the hTopo IIα enzyme, similar to the reference drug etoposide, when placed in the enzyme's active site. In addition, in silico ADME/Tox studies were carried out to assess the drug-likeness and pharmacokinetic properties of the molecules. The limonene-bis(isoxazole)-thiazolidinone hybrid derivatives may serve as promising lead compounds for the development of new topoisomerase-targeted anticancer agents. [ABSTRACT FROM AUTHOR]

Heat shock protein 90 (Hsp90), a molecular chaperone, contributes to the preservation of folding, structure, stability, and function proteins. In this study, novel compounds comprising isoxazole structure were designed, synthesized and their potential ability as Hsp90 inhibitors was validated through docking studies. The active site-based compounds were prepared through a multi-step synthesis process and their chemical structures were characterized employing FT-IR, NMR, and mass spectrometry analysis. Cytotoxic and Hsp90 inhibition activities of synthesized compounds were assessed by MTT assay and ELISA kit, respectively. Based on the obtained results, compound 5 exhibited the highest cytotoxicity (IC50; 14 µM) against cancer cells and reduced Hsp90 expression from 5.54 ng/mL in untreated (normal cells) to 1.56 ng/mL in cancer cells. Moreover, molecular dynamics (MD) simulation results indicated its high affinity to target protein and approved its excellent stability which is essential for exerting an inhibitory effect on cancer cell proliferation. [ABSTRACT FROM AUTHOR]

(3‐(4‐Fluorophenyl)oxyran‐2‐yl)(naphthalene‐2‐yl)methanone 2 was prepared from the reaction of 3‐(4‐fluorophenyl)‐1‐(naphthalen‐2‐yl)prop‐2‐en‐1‐one (1) with hydrogen peroxide and reacted with different nucleophiles such as hydrazine hydrate, phenyl hydrazine, thiosemicarbazide to give 4‐hydroxy‐1H‐pyrazole derivatives 3a,b‐4. Also, compound 2 was treated with hydroxylamine hydrochloride to give the substituted 2,3‐dihydroisoxazole 5. Similarly, compound 2 was treated with carbon disulfide, phenyl isothiocyanate, and phenyl isocyanate to give the corresponding compounds 6–8. Various spectroscopic techniques and elemental analysis were used to determine the molecular structures of the new derivatives. All the new analogs were screened against five human pathogenic microbial strains: Escherichia coli and Pseudomonas aeruginosa as Gram‐negative bacteria, Bacillus subtilis and Staphylococcus aureus as Gram‐positive bacteria and the yeast Candida albicans using agar diffusion method. Compound 4 exhibited moderate antimicrobial activity against all the tested microorganisms compared to positive control ciprofloxacin and fluconazole. On the other hand, the free radical scavenging activity of the new compounds using DPPH assay protocol revealed that most of the compounds have a weak reducing activity. Moreover, compounds 4 and 8 were docked against 1KZN protein (DNA gyrase), 3FYV and 5V5Z showing the ability to interact with key amino acid residues and the potential to act as inhibitors. [ABSTRACT FROM AUTHOR]

In response to the need for scaffolds for medical applications, synthetic chemists have developed simple and efficient methods for optimal synthesis. To investigate the synthesis of fused isoxazoles in the presence of [3+2] cycloaddition followed by C−N bond formation reaction between 3‐((4‐iodo‐3‐phenylisoxazol‐5‐yl)methyl)quinazolin‐4(3H)‐one and various nitrile oxides was carried out by previously reported conditions. The cancer activities of the synthesized compounds were then tested in vitro against two cancer cell lines, MCF‐7 and A‐549. Three of the compounds, 3‐(3,5‐dichlorophenyl) isoxazolo[4′,5′:3,4]pyrrolo[2,1‐b]quinazolin‐9(11H)‐one, 3‐(4‐fluorophenyl)isoxazolo[4′,5′:3,4]pyrrolo[2,1‐b]quinazolin‐9(11H)‐one, and 3‐(4‐(trifluoromethyl)phenyl)isoxazolo[4′,5′:3,4] pyrrolo[2,1‐b] quinazolin‐9(11H)‐one has shown superior activity against the non‐small‐cell lung cancer cell line (A‐549) than the standards 5‐fluorouracil and erlotinib. Later, in vitro EGFR results revealed that a more potent compound was more effective than the conventional medicine, erlotinib. In silico investigations of more potent compounds and erlotinib on the EGFR protein indicated that more potent compounds had comparable binding energies and inhibition constants to erlotinib. [ABSTRACT FROM AUTHOR]

Herein, we report a new method for the synthesis of functionalized pyrrole and isoquinoline derivatives using isoxazole based precursors. The reaction proceeds through the ring opening and ring closing cascade mechanism (ROCC) to afford pyrrole or isoquinoline derivatives in good to excellent yields under very mild experimental conditions. Product outcome relies on the strategic placement of different substituents on the isoxazole moiety. The present method is also applicable to synthesize functionalized isoquinolone derivatives. [ABSTRACT FROM AUTHOR]

Background: This research centers on the development and spectroscopic characterization of new quinazolin-4(3H)-one-isoxazole derivatives (5a–e). The aim was to investigate the regioselectivity of the 1,3-dipolar cycloaddition involving arylnitriloxides and N-propargylquinazolin-4(3H)-one, and to assess the antioxidant properties of the synthesized compounds. The synthetic approach started with the alkylation of quinazolin-4(3H)-one using propargyl bromide, followed by a 1,3-dipolar cycloaddition reaction. Methods: The structural identification of the products was performed using various spectroscopic methods, such as IR, 1H, 13C, and HMBC NMR, HRMS, and single-crystal X-ray diffraction. To further examine the regioselectivity of the cycloaddition, Density Functional Theory (DFT) calculations at the B3LYP/6-31G(d) level were employed. Additionally, the antioxidant potential of the compounds was tested in vitro using DPPH (2,2-Diphenyl-1-picrylhydrazyl)radical scavenging assays. The reaction selectively produced 3,5-disubstituted isoxazoles, with the regiochemical outcome being independent of the substituents on the phenyl ring. Results: Theoretical calculations using DFT were in agreement with the experimental results, revealing activation energies of −81.15 kcal/mol for P-1 and −77.32 kcal/mol for P-2, favoring the formation of P-1. An analysis of the Intrinsic Reaction Coordinate (IRC) confirmed that the reaction proceeded via a concerted but asynchronous mechanism. The antioxidant tests demonstrated that the synthesized compounds exhibited significant radical scavenging activity, as shown in the DPPH assay. The 1,3-dipolar cycloaddition of arylnitriloxides with N-propargylquinazolin-4(3H)-one successfully resulted in novel 3,5-disubstituted isoxazoles. Conclusions: The experimental findings were well-supported by theoretical predictions, and the antioxidant assays revealed strong activity, indicating the potential for future biological applications of these compounds. [ABSTRACT FROM AUTHOR]

A large series of previously unknown isoxazole containing difluoroboron β‐diketonate has been designed and synthesized from the available starting compounds. The photophysical properties of obtained compounds were studied, and the effects of the substituents in aromatic and isoxazole cycles of the BF2 complexes on the fluorescence were investigated. The effect of solvatochromism were demonstrated. Cytotoxic activity against MCF‐7 (breast carcinoma), HCT‐116 (colon carcinoma), A549 (pulmonary carcinoma) and WI38 (fibroblasts from lung tissue) cell lines was tested and moderate toxicity in the concentration range of 10–100 μM was found for several compounds. [ABSTRACT FROM AUTHOR]

Abstract Heat shock protein 90 (Hsp90), a molecular chaperone, contributes to the preservation of folding, structure, stability, and function proteins. In this study, novel compounds comprising isoxazole structure were designed, synthesized and their potential ability as Hsp90 inhibitors was validated through docking studies. The active site-based compounds were prepared through a multi-step synthesis process and their chemical structures were characterized employing FT-IR, NMR, and mass spectrometry analysis. Cytotoxic and Hsp90 inhibition activities of synthesized compounds were assessed by MTT assay and ELISA kit, respectively. Based on the obtained results, compound 5 exhibited the highest cytotoxicity (IC50; 14 µM) against cancer cells and reduced Hsp90 expression from 5.54 ng/mL in untreated (normal cells) to 1.56 ng/mL in cancer cells. Moreover, molecular dynamics (MD) simulation results indicated its high affinity to target protein and approved its excellent stability which is essential for exerting an inhibitory effect on cancer cell proliferation.

Abstract Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that affects the elderly population globally and there is an urgent demand for developing novel anti-AD agents. In this study, a new series of indole-isoxazole carbohydrazides were designed and synthesized. The structure of all compounds was elucidated using spectroscopic methods including FTIR, 1H NMR, and 13C NMR as well as mass spectrometry and elemental analysis. All derivatives were screened for their acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activity. Out of all synthesized compounds, compound 5d exhibited the highest potency as AChE inhibitor with an IC50 value of 29.46 ± 0.31 µM. It showed significant selectivity towards AChE, with no notable inhibition against BuChE. A kinetic study on AChE for compound 5d indicated a competitive inhibition pattern. Also, 5d exhibited promising BACE1 inhibitory potential with an IC50 value of 2.85 ± 0.09 µM and in vitro metal chelating ability against Fe3+ . The molecular dynamic studies of 5d against both AChE and BACE1 were executed to evaluate the behavior of this derivative in the binding site. The results showed that the new compounds deserve further chemical optimization to be considered potential anti-AD agents.

A series of novel quinoline-isoxazole hybrids 6a–o has been synthesized via multistep synthetic approach involving hetero Diels-alder reaction strategy. The target compounds were obtained in good yield, using low-cost readily available starting materials using simple reaction conditions. The newly synthesized compounds were confirmed using 1H NMR,13C NMR, and Mass spectroscopic analysis techniques. Further, compounds 6a–o were subjected to in vitro antimicrobial screening against various bacterial and fungal strains, such as Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Salmonella typhi, Aspergillus niger, and Candida albicans. Among these, compounds 6i, 6j, and 6 l were found most active having equally potent compared to standard drug Ampicillin and Gentamycin. Moreover, in silico studies of 6a–o with E. coli DNA gyrase through molecular docking and MD simulations showed excellent binding properties of these derivatives with protein site. [ABSTRACT FROM AUTHOR]

We synthesized some novel isoxazole azo derivatives using conventional methods and studied their linear, non‐linear optical properties and antioxidant activity. UV‐Vis spectroscopy revealed absorption bands ranging from 310–470 nm for the obtained compounds. Compounds 3 c and 3 b, for example, showed a large redshift and solvatochromic behavior. NLO analysis results show that compounds exhibit a greater NLO response than the magnitude of urea done by the DFT method. The electrochemical properties of compounds are studied using cyclic voltammetry and results are used for calculation of HOMO and LUMO experimentally. The antioxidant activity of the synthesized azo dyes displayed that 3 c has excellent antioxidant activity with the highest percentage (71.54605 %) of radical inhibition as compared to reference standard Vit‐C. Molecular docking analysis shows that compounds have a strong binding affinity in the range of −7.0 to −4.6 kcal/mol compared to Vit‐C, which has a binding affinity of −3.6 kcal/mol. The sun protection factor performance was determined by UV‐Vis spectroscopy, and results show that compounds are most effective, exhibit a remarkable SPF value, and offer superior sun protection by absorbing UV rays. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that affects the elderly population globally and there is an urgent demand for developing novel anti-AD agents. In this study, a new series of indole-isoxazole carbohydrazides were designed and synthesized. The structure of all compounds was elucidated using spectroscopic methods including FTIR, 1H NMR, and 13C NMR as well as mass spectrometry and elemental analysis. All derivatives were screened for their acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activity. Out of all synthesized compounds, compound 5d exhibited the highest potency as AChE inhibitor with an IC50 value of 29.46 ± 0.31 µM. It showed significant selectivity towards AChE, with no notable inhibition against BuChE. A kinetic study on AChE for compound 5d indicated a competitive inhibition pattern. Also, 5d exhibited promising BACE1 inhibitory potential with an IC50 value of 2.85 ± 0.09 µM and in vitro metal chelating ability against Fe3+. The molecular dynamic studies of 5d against both AChE and BACE1 were executed to evaluate the behavior of this derivative in the binding site. The results showed that the new compounds deserve further chemical optimization to be considered potential anti-AD agents. [ABSTRACT FROM AUTHOR]

A series of novel hybrid derivatives of spirochromanone and isoxazole/isoxazoline was synthesized by 1,3-dipolar cycloaddition of the corresponding spirochromanone alkyne/alkene with nitrile oxides, in situ generated from substituted oximes in the presence of eco-friendly oxidant (sodium hypochlorite) under mild reaction conditions. All new compounds were structurally characterized by 1H, 13C NMR and HRMS techniques. All synthesized compounds were evaluated for their antimicrobial and antifungal activities. [ABSTRACT FROM AUTHOR]

This review delves into the multifaceted biological activity of isoxazole, a versatile heterocyclic compound that has garnered significant attention in the realm of medicinal chemistry. Isoxazole derivatives have exhibited a wide array of pharmacological properties, ranging from antimicrobial and anti‐inflammatory activities to anticancer and neuroprotective effects. This comprehensive examination aims to provide a detailed overview of the molecular mechanisms underlying the biological actions of isoxazole, exploring its potential as a promising scaffold for drug development. The review encompasses recent advancements, structure‐activity relationships, and key findings from both in vitro and in vivo studies, offering insights into the therapeutic potential of isoxazole in various disease contexts. By synthesizing the current state of knowledge, this article aims to serve as a valuable resource for researchers and practitioners interested in the medicinal significance of isoxazole and its derivatives. [ABSTRACT FROM AUTHOR]

Lapachol is a proven anticancer medication ingredient that has been removed from the market due to its toxicity, but cannot disregard its therapeutic properties. Aiming to search for potent anticancer derivative of lapachol with a harmless impact, a series of novel isoxazoles derivatives were synthesized by its chemical modification. Alkylation of the hydroxyl group of lapachol gave its propargyl ether which, via copper-catalyzed cycloaddition (CuAAC) click chemistry with different oximes, afforded naphthoquinonolyl isoxazole derivatives. Molecular docking study of lapachol and its newly synthesized derivatives was also performed for potential inhibitory action toward PKM2 enzyme. All compounds showed good docking results. Among these synthesized lapachol derivatives, compound 7c showed the highest binding affinity and followed all drug rules. These findings indicated that the introduction of isoxazole fragment to the lapachol may have a significant impact on pyruvate levels in cancer cells and provides further directions for future research to find new lapachol analogues suitable for cancer treatment. [ABSTRACT FROM AUTHOR]

Alkaloid-based urea derivatives were produced with high yield through the reaction of anabasine and cytisine with isoxazolylphenylcarbamates in boiling benzene. Their antitumor activity, in combination with the commonly used five anticancer drugs, namely cyclophosphane, fluorouracil, etoposide, cisplatin, ribomustine with different mechanisms of action, was investigated. Based on the quantum chemical calculations data and molecular docking, hypotheses have been put forward to explain their mutual influence when affecting C6 rat glioma model cells. [ABSTRACT FROM AUTHOR]

Two 3-(p-substituted phenyl)-3a,8a-dihydro-4H-cyclohepta[d]isoxazoles were synthesized by 1,3-dipolar cycloaddition of the corresponding nitrile oxides with cycloheptatriene. Two endoperoxides were synthesized as facially selective and single products in high yields (93%--95%) from the reactions of isoxazole derivatives with singlet oxygen. The exact configurations of the endoperoxide with a methyl group in the phenyl ring and the diol synthesized from it were confirmed by X-ray analysis. To elucidate the mechanism, the formation energy of the endoperoxide was investigated by simulations using the software package Gaussian 09 and density functional theory calculations via the M06-2X/6-311+G(d,p) level method in dichloromethane. The results were consistent with experimental findings showing the formation of isoxazole products. [ABSTRACT FROM AUTHOR]

In this study, 56 isoxazole derivatives were synthesized and their antitumor activity against 9 cancer cells, such as BXPC-3, MiaPaCa-2, PANC-1, MCF-7, HCT-116, HepG2, NCI-H460, A549 and B16 was detected. The results of pharmacological experiments indicated that most compounds exhibit good cytotoxicity against nine cancer cells. Among them, compound 14–3 has an IC50 of 2.4 μM for colon cancer cells HCT-116, which shows the best effect and is better than the broad-spectrum drug 5-Fluorouracil (5-Fu) for the treatment of colon cancer. In addition, 14–3 induces apoptosis and leads to cell cycle arrest in the G2/M phase. Cytotoxicity tests on human normal hepatocytes LO2 also demonstrates that 14–3 is less toxic than 5-Fu with no obvious toxicity. These results suggest that 14–3 is a potential candidate for the development of anti-tumor drugs.

Background: The present study is aimed to investigate the anti-inflammatory activities of thirteen substituted-isoxazole derivatives (5a–5m). Isoxazole is a key pharmacophore in medicinal chemistry, known for its broad range of pharmacological activities.This study explores the synthesis and anti-inflammatory potential of thirteen substituted-isoxazole derivatives (5a–5m), with 5c, 5d, 5e, and 5g being novel compounds. Objectives: The primary objectives were to synthesize some novel substituted isoxazole derivatives, evaluate their interaction with cyclooxygenase (COX-1/2) enzymes through computational methods, and assess their anti-inflammatory effectiveness in laboratory animals. Methods: Substituted chalcones (0.01 mol) (2a-2m), sodium ethoxide (0.01 mol), and hydroxylamine hydrochloride (0.01 mol) were dissolved in absolute ethanol (15 ml), and then the mixture was refluxed for 6 h in an oil bath and monitored by TLC (ethyl acetate:hexane 7:3 v/v as eluent; a UV lamp was used to visualize the plates). After the completion of the reaction, as per TLC, the contents of the reaction mixture were poured into ice-cold water (50 ml). The obtained precipitates were filtered, washed two times, dried for 2 h at room temperature, and then recrystallized with ethenol. The structures of these compounds were confirmed via Fourier transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance (1H NMR) spectroscopy, carbon-13 nuclear magnetic resonance (13C NMR) spectroscopy, and mass spectrometry. Anti-inflammatory activity was evaluated using the carrageenan-induced rat paw edema method. Results: The results indicated that three compounds (5b, 5c, and 5d) demonstrated significant in vivo anti-inflammatory potential (% edema inhibition 75.68, 74.48, & 71.86 in 2 h and 76.71, 75.56, & 72.32 in 3 h) with modest effectiveness (0.83, 0.81 & 0.71), low toxicity, and minimal adverse effects. The molecular docking analyses further elucidated the interaction with the active site COX-2 enzyme (PDB ID: 4COX) using Autodock Vina. The compounds 5b, 5c, and 5d −8.7, −8.5, and −8.4 indicate good binding affinity (kcal/mol) and H-bond interaction with residues such as Cys41, Ala151, and Arg120 for COX-2, which also carried out RMSD values of 2.174, 41.13, and 22.25, which are decisive for the reported anti-inflammatory activity of diverse compounds. Conclusions: The findings indicate that isoxazole derivatives have modest antiinflammatory potential, with compounds (5b, 5c, and 5d) acting as lead molecules to be studied further for pain relief with fewer adverse effects.

Novel isoxazole–triazole conjugates have been efficiently synthesized using 3-formylchromone as starting material according to a multi-step synthetic approach. The structures of the target conjugates and intermediate products were characterized by standard spectroscopic techniques (1H NMR and 13C NMR) and confirmed by mass spectrometry (MS). The all-synthesized compounds were screened for their antibacterial activity against three ATCC reference strains, namely Staphylococcus aureus ATCC 25923, Staphylococcus aureus ATCC BAA-44, and Escherichia coli ATCC 25922 as well as one strain isolated from the hospital environment Pseudomonas aeruginosa. The findings indicate that conjugate 7b exhibits a stronger antibacterial response against the tested Escherichia coli ATCC 25922 and Pseudomonas aeruginosa pathogenic strains compared to the standard antibiotics. Furthermore, hybrid compound 7b proved to have a bactericidal action on the Escherichia coli ATCC 25922 strain, as evidenced by the results of the MBC determination. Moreover, the ADMET pharmacokinetic characteristics revealed a favorable profile for the examined compound, as well as a good level of oral bioavailability. Molecular docking and molecular dynamics simulations were performed to explore the inhibition mechanism and binding energies of conjugate 7b with the proteins of Escherichia coli and Pseudomonas aeruginosa bacterial strains. The in silico results corroborated the data observed in the in vitro evaluation for compound 7b. [ABSTRACT FROM AUTHOR]

In this study, we have focused on the preparation and application of a nano-ferric oxide catalyst as a heterogeneous catalyst in the one-pot, three-component synthesis of isoxazole derivatives. The ferric oxide catalyst was synthesized using a simple precipitation method and thoroughly characterized using techniques such as FT-IR, XRD, SEM, EDX, and BET. The effectiveness of the ferric oxide catalyst as a heterogeneous catalyst was investigated in the synthesis of 3,4,5-trisubstituted isoxazole. The results of the synthesis demonstrated that the catalyst exhibited high efficiency in facilitating the three-component, one-pot synthesis of 3,4,5-trisubstituted isoxazole derivatives. The synthesis route employed in this study offers several advantages, including its simplicity, ease of workup, and environmental friendliness. Furthermore, the catalyst was successfully recovered and reused for five cycles without experiencing a significant loss in catalytic activity. This finding highlights the excellent stability and promising potential of the catalyst for organic transformations. Overall, our study showcases the successful preparation and application of the nano-ferric oxide catalyst in the synthesis of isoxazole derivatives, providing valuable insights into its catalytic performance and potential for future applications in organic chemistry. [ABSTRACT FROM AUTHOR]

This review presents an outline of current advancements in the photochemical and electrochemical synthesis of oxazoles and isoxazoles. Oxazole and isoxazole are important building blocks for a variety of medicinally useful compounds. Therefore, the synthesis of these heterocycles via sustainable technologies is worth demanding. Photochemical and electrochemical are two among the few sustainable technologies. This review covers a brief discussion on reaction parameters like catalysts, substrates scope, reaction temperature, solvents, electrodes, electrolytes (in case of electrochemical process), light source (in case of photochemical process) for individual reaction. Detailed discussion on mechanistic insight for each reaction is also presented. Finally, summary, and future direction toward the development of effective electrochemical and photochemical methods for the reaction of oxazoles and isoxazoles is also presented. [ABSTRACT FROM AUTHOR]

[Display omitted] Reactions between 4-(propargyloxy)benzaldehyde with anthracene-9-carbaldehyde oxime or pyrene-1-carbaldehyde oxime in the presence of chloramine T in ethanol lead to new isoxazole-containing derivatives of benzaldehyde. The subsequent acid-catalyzed condensation of these compounds with 2-methylresorcinol in chloroform/trifluoroacetic acid mixtures affords novel calix[4]resorcinols with anthaceneand pyrene-ended isoxazole-containing fragments as all– cis (rccc) and cis–trans–trans (rctt) diastereoisomers, their ratios being dependent on the CF 3 CO 2 H percentage in the medium. The crystal structures of pyrene-ended isoxazole-containing benzaldehyde and corresponding calix[4]resorcinol rctt isomer have been established by single crystal X-ray diffraction. [ABSTRACT FROM AUTHOR]

Introduction and aim. The synthesis of heterocyclic compounds containing oxygen and nitrogen is profoundly intriguing due to their mechanistic implications in both research and development within organic chemistry and drug discovery. The primary aim of this study is to fabricate a range of pharmacologically active drugs containing the isoxazole moiety. Material and methods. The synthesis of new derivatives of isoxazole was achieved through a one-pot condensation reaction of 2-[(Substituted phenyl)hydrazono]malononitrile (1) and 3-[(Substituted phenyl)azo]-2,4-Pentanedione (2) with sodium acetate and hydroxylamine hydrochloride (1:1) in ethanol. All the compounds were screened for their in vitro antibacterial activity, in vitro antioxidant and anticancer activity. The synthesized compounds underwent characterization through FTIR, 1 H NMR, and 13C NMR analyses, supported by mass spectral data and elemental analysis. Results. A set of novel isoxazole derivatives was synthesized with a favorable yield. Among compounds 1d, 1e, 2c, 2d, and 2e exhibited notable antioxidant activities. Compounds 1a, 1b, and 1c demonstrated significant anticancer potential against prostate cancer [PC3] cell lines compared to normal HEK cell lines, while 2a displayed the highest inhibitory zone against Escherichia coli. Conclusion. Novel compounds with multifaceted biological activities have been successfully designed, and a synthetic route to create isoxazole derivatives has been devised and verified. [ABSTRACT FROM AUTHOR]

Introduction: The determination of biotransformation products is an essential part of the preclinical trial of original medicines. These studies have not been conducted before for the new drug 5-[5-(trifluoromethyl)-1,2-oxazole-3-yl]-furan-2-sulfonamide. Identification and synthesis of metabolite substances are necessary for subsequent tests of bioavailability, linearity of pharmacokinetics, accumulation, distribution and excretion. Materials and methods: The study was carried out on Wistar rats and rabbits of the Soviet Chinchilla breed. The substance of the drug was administered to animals intraperitoneally. The collection of animal blood samples was performed before administration and 1 h, 2 h, 4 h, 24 h after administration into K3EDTA-tubes. A part of each sample was centrifuged to separate the plasma. Rat urine samples were taken before administration and at intervals of 0-2 h, 2-4 h, 4-6 h, 6-24 h after administration of the drug. The HPLC-MS/MS method was used to identify metabolites in biological fluids. The assumed biotransformation products were synthesized after preliminary analysis. The structure of the obtained substances was confirmed by NMR spectroscopy and high-resolution mass spectrometry. Then, a comparison was carried out with the compounds identified in biological fluids by retention time, ratios of chromatographic peak areas at the main MRM-transitions using HPLC-MS/MS. Results and discussion: A metabolite formed by addition an oxygen atom to a drug molecule, as well as an acylated metabolite were detected during the analysis of plasma and blood samples. A compound with an increased molecular weight of 1 dalton compared to the drug substance was also present in a rat urine. N-hydroxy-5-[5-(trifluoromethyl)-1,2-oxazole-3-yl]-furan-2-sulfonamide, 5-[5-(trifluoromethyl)-1,2-oxazole-3-yl]-furan-2-sulfonic acid, which could potentially be obtained during biotransformation, as well as N-acetyl-5-[5-(trifluoromethyl)-1,2-oxazole-3-yl]-furan-2-sulfonamide were synthesized. Repeated HPLC-MS/MS tests confirmed the correctness of the initial hypothesis. It was found that a sulfonic acid derivative is formed in urine as a result of decomposition of N-hydroxymetabolite during sample collection. Conclusion: The studied drug is metabolized by formation of two metabolites: N-hydroxy-5-[5-(trifluoromethyl)-1,2-oxazole-3-yl]-furan-2-sulfonamide and N-acetyl-5-[5-(trifluoromethyl)-1,2-oxazole-3-yl]-furan-2-sulfonamide. N-hydroxymetabolite is able to decompose in biological fluids samples with formation of 5-[5-(trifluoromethyl)-1,2-oxazole-3-yl]-furan-2-sulfonic acid.

Background: This research centers on the development and spectroscopic characterization of new quinazolin-4(3H)-one-isoxazole derivatives (5a–e). The aim was to investigate the regioselectivity of the 1,3-dipolar cycloaddition involving arylnitriloxides and N-propargylquinazolin-4(3H)-one, and to assess the antioxidant properties of the synthesized compounds. The synthetic approach started with the alkylation of quinazolin-4(3H)-one using propargyl bromide, followed by a 1,3-dipolar cycloaddition reaction. Methods: The structural identification of the products was performed using various spectroscopic methods, such as IR, 1H, 13C, and HMBC NMR, HRMS, and single-crystal X-ray diffraction. To further examine the regioselectivity of the cycloaddition, Density Functional Theory (DFT) calculations at the B3LYP/6-31G(d) level were employed. Additionally, the antioxidant potential of the compounds was tested in vitro using DPPH (2,2-Diphenyl-1-picrylhydrazyl)radical scavenging assays. The reaction selectively produced 3,5-disubstituted isoxazoles, with the regiochemical outcome being independent of the substituents on the phenyl ring. Results: Theoretical calculations using DFT were in agreement with the experimental results, revealing activation energies of −81.15 kcal/mol for P-1 and −77.32 kcal/mol for P-2, favoring the formation of P-1. An analysis of the Intrinsic Reaction Coordinate (IRC) confirmed that the reaction proceeded via a concerted but asynchronous mechanism. The antioxidant tests demonstrated that the synthesized compounds exhibited significant radical scavenging activity, as shown in the DPPH assay. The 1,3-dipolar cycloaddition of arylnitriloxides with N-propargylquinazolin-4(3H)-one successfully resulted in novel 3,5-disubstituted isoxazoles. Conclusions: The experimental findings were well-supported by theoretical predictions, and the antioxidant assays revealed strong activity, indicating the potential for future biological applications of these compounds.

Intramolecular cycloadditions have the great advantage of forming two rings simultaneously. We report the use of intramolecular [3 + 2] cycloaddition of the nitrile oxide derived from an N-propargylbenzimidazole oxime in the synthesis of a hitherto unreported tetracyclic isoxazole-containing ring system bearing "6-5-5-5"-membered ring fusions. The initial condensation was achieved through reaction of o-phenylenediamine with ethyl diethoxyacetate, followed by alkylation with propargyl bromide, deprotection of the acetal to the aldehyde, formation of an aldoxime, and intramolecular nitrile oxide cycloaddition (INOC). Characterization of the aldoxime and tetracyclic isoxazole is included herein. [ABSTRACT FROM AUTHOR]

In pursuit of unsymmetrical precursors for the novel series of anthracenyl-isoxazole amide (AIM) antitumor agents, a series of substituted anthracenes were subjected to bromination and re-aromatization in our study, during which we solved four single crystal X-ray diffractometry (Sc-xrd) structures which we report herein. The C-9 nitrile oxide, after its reaction with bromine, was isolated, but when subjected to re-aromatization, it returned to the starting 10-bromo nitrile oxide 1, which did provide an accurate crystal structure, with R = 0.018. The 10-halogenated 3-(9'-anthryl)-isoxazole esters were subjected to bromination and re-aromatization. Surprisingly, the yields obtained in the presence of the isoxazole were reasonably good (62–68% isolated yields), and the major diastereomers allowed for the characterization using Sc-xrd. The penta bromo product 2 showed a trans, trans, cis relationship for the four bromines on the A-ring of the anthracene, and we observed that for the unit cell, the atropisomers displayed a 1:1 ratio at the chiral axis between the isoxazole and anthrancene rings. Similarly, the 10-chloro 3 indicated a ratio of 1:1 at the chiral axis in the crystal structure. A base-induced re-aromatization afforded 3,10-dihalogenated analogues selectively in very good yields (X = Cl, 89%; X = Br 92%), of which the dibromo 4 was characterized using Sc-xrd. The improved yields of the unique diastereomeric bromination products suggested the consideration of a novel electrophilic aromatic substitution mechanism driven by the stereo-electronic environment, imposed by the isoxazole ester substituent. The promise of the application of this chemistry in the future development of AIM antitumor agents is suggested. [ABSTRACT FROM AUTHOR]

A series of 2‐(1‐substituted benzyl‐1H‐1,2,3‐triazol‐4‐yl)‐1‐(5‐arylisoxazol‐3‐yl)ethanol (8 a–p) have been designed and efficiently synthesized. The structure of the compounds 8 a–p was characterized by spectral methods. The newly synthesized 1,2,3‐triazolyl‐isoxazolyl‐ethanol (8 a–p) derivatives were evaluated for in vitro antimicrobial activity against P. mirabilis, E. coli, S. albus, B. subtilis, C. albicans and A. niger. Eleven derivatives showed good activity against the Gram‐negative strains. Compounds 8 b, 8 c, 8 d, 8 g, 8 h, 8 i, 8 j, 8 k, 8 n, 8 o, and 8 p showed good antibacterial against E. coli activity. Against P. mirabilis, compounds 8 a, 8 b, 8 d, 8 g, 8 h, 8 k, 8 l, 8 m, 8 n, 8 o, and 8 p showed good activity, compounds 8 o, and 8 p showed two‐fold less activity than the reference drug streptomycin. Against the Gram‐positive strain, B. subtilis, compounds 8 c, 8 d and 8 f showed good activity, from which the compounds 8 d and 8 f were found only two‐fold less potent than the reference drug streptomycin. Against fungal strains, C. albicans, compound 8 g and against A. niger, compounds 8 f, 8 h and 8 j showed good antifungal activity. Against A. niger strain, the compounds 8 f and 8 h reported only two‐fold less activity than the reference drug fluconazole. The active compounds were studied for molecular docking and molecular dynamics simulations. [ABSTRACT FROM AUTHOR]

Isoxazolidine, isoxazole, and isoquinolinone rings are present in the structure of several natural products and/or pharmaceutically interesting compounds. In this work, facile and efficient pathways have been developed for the preparation of fused frameworks bearing those heterocycles. The successful approaches for both isoxazolidine/isoquinolinone and isoxazole/isoquinolinone hybrid syntheses relied initially on 1,3-dipolar cycloadditions of nitrones and nitrile oxides to indenone and 2-propargylbenzamide, respectively. The construction of the isoquinolinone lactam system followed by performing a selective Schmidt reaction for isoxazolidine derivatives (two steps overall), whereas the isoxazole lactams were reached via an Ullmann-type cyclisation (three steps overall). Key observations were made regarding the stereo- and regioselectivities of the reactions employed, and small libraries of the targeted hybrids were prepared, demonstrating the general applicability of these strategies. [ABSTRACT FROM AUTHOR]

New 1,3-disubstituted 2,2-dimethylcyclopropanes of the isoxazole and pyrazole series were synthesized starting from (+)-3-carene. Olefination of the reductive ozonolysis product of (+)-4-acetyl-2-carene produced 1R-cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane, further reaction of which with hydroxylamine or hydrazines led to heterocyclic compounds. It was shown that 3,5-dimethylpyrazoles could be synthesized on the surface of Al2O3 using ultrasonic irradiation. Studies of the antimicrobial activity of heterocyclic derivatives of dibromovinyl-2,2-dimethylcyclopropane found significant fungicidal effects of pyrazoles 8, 10, and 11 with weak antibacterial activity. [ABSTRACT FROM AUTHOR]

Introduction: The determination of biotransformation products is an essential part of the preclinical trial of original medicines. These studies have not been conducted before for the new drug 5-[5-(trifluoromethyl)-1,2-oxazole-3-yl]-furan-2-sulfonamide. Identification and synthesis of metabolite substances are necessary for subsequent tests of bioavailability, linearity of pharmacokinetics, accumulation, distribution and excretion. Materials and methods: The study was carried out on Wistar rats and rabbits of the Soviet Chinchilla breed. The substance of the drug was administered to animals intraperitoneally. The collection of animal blood samples was performed before administration and 1 h, 2 h, 4 h, 24 h after administration into K3EDTA-tubes. A part of each sample was centrifuged to separate the plasma. Rat urine samples were taken before administration and at intervals of 0-2 h, 2-4 h, 4-6 h, 6-24 h after administration of the drug. The HPLC-MS/MS method was used to identify metabolites in biological fluids. The assumed biotransformation products were synthesized after preliminary analysis. The structure of the obtained substances was confirmed by NMR spectroscopy and high-resolution mass spectrometry. Then, a comparison was carried out with the compounds identified in biological fluids by retention time, ratios of chromatographic peak areas at the main MRM-transitions using HPLC-MS/MS. Results and discussion: A metabolite formed by addition an oxygen atom to a drug molecule, as well as an acylated metabolite were detected during the analysis of plasma and blood samples. A compound with an increased molecular weight of 1 dalton compared to the drug substance was also present in a rat urine. Nhydroxy-5-[5-(trifluoromethyl)-1,2-oxazole-3-yl]-furan-2-sulfonamide, 5-[5-(trifluoromethyl)-1,2-oxazole-3-yl]-furan-2-sulfonic acid, which could potentially be obtained during biotransformation, as well as N-acetyl-5-[5-(trifluoromethyl)-1,2-oxazole-3-yl]-furan-2-sulfonamide were synthesized. Repeated HPLC-MS/MS tests confirmed the correctness of the initial hypothesis. It was found that a sulfonic acid derivative is formed in urine as a result of decomposition of N-hydroxymetabolite during sample collection. Conclusion: The studied drug is metabolized by formation of two metabolites: N-hydroxy-5-[5-(trifluoromethyl)-1,2-oxazole-3-yl]-furan-2-sulfonamide and N-acetyl-5-[5-(trifluoromethyl)-1,2-oxazole-3-yl]-furan-2-sulfonamide. N-hydroxymetabolite is able to decompose in biological fluids samples with formation of 5-[5-(trifluoromethyl)-1,2-oxazole-3-yl]-furan-2-sulfonic acid. [ABSTRACT FROM AUTHOR]

Five-membered heterocycles containing nitrogen, oxygen atoms, especially isoxazoles, are widely present in many natural products and drugs and have relevant medical and pharmaceutical applications. Due to their rich biological activity, the development of novel isoxazole derivatives has been the focus of researchers and scientists. It is worth noting that a large number of isoxazoles have been used frequently as clinical drugs to treat various diseases, showing great development value and wide medicinal potential. In this review, the research progress of isoxazole natural products in anti-bacterial, anti-tuberculosis, anti-virus, anti-tumor, anti-inflammation, anti-diabetes, anti-parasite, anti-psychosis and other biological activities was reviewed. Finally, the research and development prospects of isoxazole natural products were prospected. This review will provide reference for the design of natural isoxazole products with stronger activity and less toxicity.

A library of novel sulfoximine-isoxazole hybrids was synthesized and evaluated for antimalarial activity. The subsequential synthetic pathways, which included the alkylation of thiols and simultaneous sulfide oxidation and imination, yielded a library of sulfoximine derivatives 3a-s. These were coupled with brominated-isoxazoles 6a-c, to give sulfoximine-isoxazole hybrids 7a-v and further derivatized to compounds 8 and 9. The hybrid compounds were then investigated for their antiplasmodial activity against the wild-type drug-sensitive strain (NF54) and multidrug-resistant strain (K1). Only six (6) hybrids showed minor potency against the drug-sensitive and drug-resistant strains (IC50 values ranging between 4.1 and 5.8 μM). The selectivity studies indicated no significant toxicity of the hybrid compounds against mammalian cells.

Alkaloid-based urea derivatives were produced with high yield through the reaction of anabasine and cytisine with isoxazolylphenylcarbamates in boiling benzene. Their antitumor activity, in combination with the commonly used five anticancer drugs, namely cyclophosphane, fluorouracil, etoposide, cisplatin, ribomustine with different mechanisms of action, was investigated. Based on the quantum chemical calculations data and molecular docking, hypotheses have been put forward to explain their mutual influence when affecting C6 rat glioma model cells.

Intramolecular cycloadditions have the great advantage of forming two rings simultaneously. We report the use of intramolecular [3 + 2] cycloaddition of the nitrile oxide derived from an N-propargylbenzimidazole oxime in the synthesis of a hitherto unreported tetracyclic isoxazole-containing ring system bearing “6-5-5-5”-membered ring fusions. The initial condensation was achieved through reaction of o-phenylenediamine with ethyl diethoxyacetate, followed by alkylation with propargyl bromide, deprotection of the acetal to the aldehyde, formation of an aldoxime, and intramolecular nitrile oxide cycloaddition (INOC). Characterization of the aldoxime and tetracyclic isoxazole is included herein.

An efficient regioselective approach to novel functionalized bis(isoxazoles) with a variety of aromatic and aliphatic linkers was elaborated, based on the heterocyclization reaction of electrophilic alkenes under the treatment with tetranitromethane-triethylamine complex affording 3-EWG-5-nitroisoxazoles. The subsequent SNAr reactions of 5-nitroisoxazoles with various O,O-, N,N- and S,S-bis(nucleophiles) provide a wide range of bis(isoxazole) derivatives in good isolated yields. Employing an elaborated method, a series of novel bis(3-EWG-isoxazoles) as the promising allosteric modulators of AMPA receptors were designed and synthesized. The effect of the compounds on the kainate-induced currents was studied in the patch clamp experiments, revealing modulator properties for several of them. The best positive modulator potency was found for dimethyl 5,5′-(ethane-1,2-diylbis(sulfanediyl))bis(isoxazole-3-carboxylate), which potentiated the kainate-induced currents in a wide concentration range (10−12–10−6 M) with maximum potentiation of 77% at 10−10 M. The results were rationalized using molecular docking and molecular dynamics simulations of modulator complexes with the dimeric ligand-binding domain of the GluA2 AMPA receptor. The predicted physicochemical, ADMET, and PAINS properties confirmed that the AMPA receptor modulators based on the bis(isoxazole) scaffold may serve as potential lead compounds for the development of neuroprotective drugs. [ABSTRACT FROM AUTHOR]

Nitrile imine derivative 3 added regioselectively to α-(benzothiazol-2-yl)cinnamonitrile derivatives 1a–c to afford 5-(benzothiazol-2-yl)-5-cyano-4,5-dihydro-1H-pyrazole derivatives 4a–c. Compound 4a underwent thermal elimination of hydrogen cyanide in sodium ethoxide solution to give the pyrazole derivative 6. The isoxazole derivative 10 was synthesized by reacting nitrile oxide 8 with cinnamonitrile derivative 1d. The structures of the synthesized compounds were characterized by FT-IR, NMR, and MS spectroscopic techniques. The reaction mechanism was studied via density functional theory (DFT) quantum chemical calculations at the B3LYP/6-31G (d) level of theory. [ABSTRACT FROM AUTHOR]

A series of previously unknown isoxazole-functionalized imidazopyridine derivatives were synthesized in a few steps, starting from pyridine-2,3-diamine. The synthesis involved the reaction of pyridine-2,3-diamine with lactic acid in PEG-400 to prepare 1-(3H-imidazo[4,5-b]pyridin-2-yl)ethanol which was further reacted with propargyl bromide to form 2-[1-(prop-2-yn-1-yloxy)ethyl]-3H-imidazo[4,5-b]pyridine. Finally, the latter was annulated with substituted benzaldehyde oximes in the presence of a catalytic amount of DBU to obtain the target 3-aryl-5-{[1-(3H-imidazo[4,5-b]pyridin-2-yl)ethoxy]methyl}-isoxazoles. The newly synthesized compounds were characterized by IR and NMR spectroscopy and mass spectrometry and showed excellent DPPH/superoxide/nitric oxide activity in antioxidant assay. [ABSTRACT FROM AUTHOR]

A powerful analgesic and anti-inflammatory agent were established by preparing a series of new heterocyclic substituted oxazole analogs. The chemical structures of the entire prepared analogs were confirmed by spectroscopic and elemental analyses. Molecular properties, ADME properties, and drug-likeness scores and toxicities of title compounds were predicted using in silico studies. In addition, title compounds were docked against two proteins namely, 3KK6, and 3LN1 using Auto Dock 4.2. In vitro analgesic and anti-inflammatory activities of prepared analogs were estimated using tail flick method and carrageenan-induced foot paw edema technique, respectively. Additionally, ulcerogenicity of potent analogs was also determined. Most of the prepared analogs showed mild-to-good analgesic and anti-inflammatory with low-to-reasonable ulcer index. Among the tested series, the most potent compound was found to be 1-(3-chlorophenyl)-3-methyl-4-(2-(4-((2-methyl-5-oxooxazol-4(5H)-ylidene) methyl)phenyl) hydrazono)-1H-pyrazol-5(4H)-one (OHPA3). [ABSTRACT FROM AUTHOR]

A new library of 6-(pyridin-4-yl)imidazo[2,1-b][1,3]thiazole derivatives (11a–11j) containing an isoxazole ring linked to C3 through a p-phenylene spacer was designed, synthesized, and tested for their in vitro anticancer activity against four human cancer cell lines, including PC3 and DU-145 (prostate cancer), A549 (lung cancer), and MCF-7 (breast cancer) by using MTT assay with etoposide as positive control. Among them, five compounds displayed more potent anticancer activity, and those bearing 3,4,5-trimethoxyphenyl and pyridin-4-yl substituents on C3 of the isoxazole ring showed most promising activity. [ABSTRACT FROM AUTHOR]

Isoxazolo[3,4-d] pyridazinones ([3,4-d]s) were previously shown to have selective positive modulation at the metabotropic glutamate receptor (mGluR) Subtypes 2 and 4, with no functional cross-reactivity at mGluR1a, mGluR5, or mGluR8. Additional analogs were prepared to access more of the allosteric pocket and achieve higher binding affinity, as suggested by homology modeling. Two different sets of analogs were generated. One uses the fully formed [3,4-d] with an N6-aryl with and without halogens. These underwent successful selective lateral metalation and electrophilic quenching (LM&EQ) at the C3 of the isoxazole. In a second set of analogs, a phenyl group was introduced at the C4 position of the [3,4-d] ring via a condensation of 4-phenylacetyl-3-ethoxcarbonyl-5-methyl isoxazole with the corresponding hydrazine to generate the 3,4-ds 2b and 2j to 2n. [ABSTRACT FROM AUTHOR]

New 1,5,3,7-diazadiphosphacyclooctanes with N,O-, N,N-, N,S-, and N,N,S-heterocyclic substituents at the nitrogen atoms have been synthesized. The influence of the nature of amines containing sp2-hybridized nitrogen atom in the ortho-position of the heterocyclic substituent on the result of Mannich condensation in phosphine–paraformaldehyde–primary amine system has been revealed. The stabilization of intermediate acyclic products—aminomethyl(hydroxymethyl)arylphosphines and bis(aminomethyl)arylphosphines—due to amino–imine tautomerism is responsible for the low yield of the target cyclic diphosphines based on the above amines. [ABSTRACT FROM AUTHOR]

The condensation of the binucleophilic reagents hydrazine hydrate and hydroxylamine hydrochloride on 3-acetoacetyl-2-methyl-pyrido[1,2-a]pyrimidin-4-one 3 acting as a heterocyclic β-diketone affords 3-azolyl-2-methyl-pyrido[1,2-a]pyrimidine derivatives 4 and 7. The alkylation of 3-pyrazolyl-pyrido[1,2-a]pyrimidin-4-one with allyl bromide under phase transfer catalysis gives exclusively 3-[(1-prop-2-en-1-yl) 5-methypyrazol-3-yl]-2-methyl-pyrido[1,2-a] pyrimidin-4-one. A plausible mechanism for the formation of the obtained compounds 4 and 7 have been proposed and discussed. [ABSTRACT FROM AUTHOR]