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The Chemical Communications journal, published by The Royal Society of Chemistry, features articles on various topics such as catalytic enantioselective construction, microbial transformation of heavy metals, and alkyne annulations. The journal also covers topics like photoswitches, ammonia adsorption, and selective photocatalytic CO2 reduction. Additionally, the journal includes articles on topics like thiazole synthesis, redox platforms, and lanthanide coordination polymers. The publication aims to uncover new possibilities and provide fundamental answers to scientific questions. [Extracted from the article]

A general and practical K2CO3-promoted [3+2] annulation between trifluoroacetaldehyde N-triftosylhydrazone (TFHZ-Tfs) and 4-nitroisoxazoles has been developed to access structurally diverse trifluoromethylpyrazolo[3,4-d]isoxazoles. Mechanistically, CF3CHN2 is formed in situ by TFHZ-Tfs decomposition and involves a formal [3+2] dearomative cycloaddition with 4-nitroisoxazoles, followed by aromatization via the elimination of the nitro group. Furthermore, this protocol is metal-free, scalable, mild, and operationally safe, with a broad substrate scope and high functional group compatibility. [ABSTRACT FROM AUTHOR]

The catalytic asymmetric electrophilic functionalization of the less reactive N-heteroaromatic compounds has been reported using the approach of the introduction of an exocyclic amino substituent. This strategy has allowed enantioselective Friedel–Crafts alkylation in pyrazoles, isoxazoles and isothiazoles, as well as in aminoindoles, aminobenzofurans and aminobenzothiophenes. Several stereoselective methods have been used for the 1,4-addition or 1,2-addition of these heteroaromatic compounds to different electrophiles employing organocatalysts or chiral metal complexes. The activating exocyclic amino substituent has also been used as a nucleophile in tandem reactions, including formal cycloadditions ([3+2] and [3+3]), for the synthesis of highly functionalized chiral nitrogen heterocycles. [ABSTRACT FROM AUTHOR]

An enantioselective arylation of isoxazoles with N‐Cbz‐protected azonaphthalenes is disclosed, affording a range of axially chiral arylisoxazoles in good yields and excellent enantiocontrol by utilizing chiral phosphoric acid. Cbz protecting group can be readily removed, resulting in five‐six membered axially chiral heterobiaryl amines bearing free amine maintaining enantiomeric purity. [ABSTRACT FROM AUTHOR]

An electrochemically promoted protocol has been successfully developed for the synthesis of 4-organoselenyl isoxazoles via the oxidative selenocyclization of 2-alkyn-1-one O-methyloximes with diorganyl diselenides as selenation reagents. A wide range of titled compounds were obtained in over 80% yields without an additional catalyst or external oxidant. In comparison with existing methods, this newly developed protocol featured broader substrate scopes, higher selectivity and more atom economy. [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]

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]

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 mechanochemical‐enabled Ru‐catalyzed regioselective synthesis of 3,4‐isoxazoles and 3,4,5‐isoxazoles from terminal and internal alkynes and hydroxyimidoyl chlorides is reported. This solid‐state and solvent‐free approach carefully examines the impact of the milling conditions on regiocontrol in 1,3‐dipolar cycloadditions using mechanochemical means. The study reveals that milling frequency, jar material, and the choice of liquid additive for liquid‐assisted grinding (LAG) significantly influence the catalytic activity of the Ru catalyst. Transmission electron microscope (TEM) analysis confirms the crucial role of coordinating liquid additives such as acetone and cyclopentyl methyl ether (CPME) in stabilizing and reducing the size of the in‐situ formed Ru nanoparticles, which is essential for catalytic activity. The applicability of this protocol is further demonstrated through the synthesis of a library of 3,4‐ and 3,4,5‐isoxazoles from a wide range of terminal and internal alkynes with varying physical states and electronic properties that highlights the potential of this method for the synthesis of more complex target molecules. [ABSTRACT FROM AUTHOR]

3‐methyl‐4‐(hetero)arylmethylidene isoxazole‐5(4H)‐one derivatives (4a‐r) derivatives (4a‐r) were synthesized by the multi‐component reactions. The multi‐component reactions (MCRs) of hydroxylamine hydrochloride, ethyl acetoacetate and aromatic/ heteroaromatic aldehyde catalyzed by novel Glutamic acid (Glu) as a biodegradable and eco‐friendly organocatalyst in ethanol on oil bath stirring at 60 °C. The final product homogeneity was examined by various spectroscopic techniques. In this work prepared compounds 4 q and 4 r are novel derivatives. The molecular dynamics of total energy and energy gap was calculated using DFT/B3LYP/6–31G (dp) method. The selected derivatives (4 l–r) screened against in vitro MCF‐7 breast cancer cell line by MTT assay, derivatives 4 l and 4 o displayed very good activity with IC50 of 6.57±2.31, and 21.93±1.34 as compared to doxorubicin of IC50 (3.69±0.17). Molecular docking studies were performed to evaluate interaction of PDB id: 1 M17 with led molecules of MCF‐7. Later, 1 M17 and 4 l underwent 200 ns molecular dynamics and simulation within physiological conditions, the outcomes showed that during the simulation, the ligand stayed in the same form. Further, the selected derivatives drug like computed using swissADME, and derivatives 4 l–r obeyed rule of Lipinski's. Furthermore, selected derivatives tested for electrochemical behavior using cyclic voltammetry, and compound 4 l and 4 q showed strong oxidation and reduction potential, thus these derivatives can present better antioxidant properties. [ABSTRACT FROM AUTHOR]

Developed here is a highly fluorescent organic N,O bidentate BF2 complex from isoxazole in the presence of a Ru(II) catalyst. Herein, the complexation proceeds via a selective N–O cleavage of the isoxazole ring. The complex shows absorption (λmax,abs) in the range of 352–363 nm with an extinction coefficient (ε) in the range of 8000–64 000 M−1 cm−1, and fluorescence emission (λmax,em) in the range of 413–485 nm with a Stokes shift of 61–125 nm having quantum yield up to 33%. Apart from the solution state, the solid BF2 complex 2u exhibits absorption at 405 nm and strong fluorescence emission at 550 nm with a quantum yield of 26.9%. [ABSTRACT FROM AUTHOR]

5-(4,5-Dihydro-1H-pyrazol-3-yl)isoxazoles (pyrazoline-isoxazoles) are readily oxidized by active manganese dioxide in benzene or dichloromethane at room temperature. As a result, a simple and efficient method for the synthesis of the corresponding pyrazoleisoxazoles in 94–99% yields was developed. It was shown that 3-ethynyl-1H-pyrazoles are inactive in the 1,3-dipolar cycloaddition reaction with nitrile oxides and nitrile imines. The synthesized di- and trisubstituted pyrazole-isoxazoles showed weaker luminescent properties compared to pyrazoline-isoxazoles. [ABSTRACT FROM AUTHOR]

Activation of the Hedgehog (Hh) signaling pathway is often associated with the progression of various types of cancer. The purpose of study was to search for inhibitors of the Hh signaling pathway among eight compounds belonging to the group of isoxazolyl steroids. The evaluation of the effectiveness of the compounds was based on the analysis of their cytotoxicity, effect on the cell cycle, on the expression of key Hh-signaling-pathway genes (Ptch1, Smo, and Gli1) and putative target genes MMP-2 and MMP-9. Four compounds with the most pronounced cytotoxic effect were identified: compounds 1, 2 (HeLa cells) and 3, 4 (A549 cells). Compounds 1 and 2 significantly reduced the expression of the Ptch1, Smo, Gli1 genes, but had the opposite effect on MMP-2 gene expression: Compound 1 increased it, and compound 2 decreased it. Compounds 3 and 4 did not have a noticeable inhibitory effect on the expression of the Shh pathway receptors, but significantly inhibited MMP-2 and MMP-9 expression. Thus, it was shown that inhibition of the Shh signaling pathway by isoxazolyl steroids can have the opposite effect on MMPs gene expression, which is what should be taken into account in further studies of these compounds as therapeutic agents. [ABSTRACT FROM AUTHOR]

This article discusses the design, synthesis, and evaluation of amide derivatives of 1,3,4-thiadiazolyl pyridinyl isoxazoles for their anticancer properties. The compounds were tested against four human cancer cell lines and showed moderate to good activity, with three compounds (13a, 13b, and 13c) exhibiting the most potent activity. Molecular docking studies were also conducted, which suggested the effectiveness of the binding mode of the Tubulin B chain receptor and these three compounds. The article provides detailed information on the synthesis process, characterization of the compounds, and their cytotoxicity results. Another document provides information on the synthesis and characterization of several compounds (13b, 13c, 13d, 13e, and 13f) with specific chemical structures. The compounds were prepared using a specific method and their physical properties, such as melting point and spectral data, were determined. The document also includes the calculated and found values for the elemental composition of each compound. A separate document provides information on the synthesis and characterization of several compounds (13g, 13h, 13i, and 13j) and their molecular docking studies. The compounds were prepared using a specific method and purified through column chromatography. The physical properties and spectroscopic data of the compounds are provided. The compounds were then subjected to molecular docking studies using PyRx software. The MTT assay was also performed to evaluate the cytotoxicity of the [Extracted from the article]

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]

The 4‐carboxylates of 1,2,3‐triazine 1‐oxides undergo [3+2] cycloaddition with in situ generated benzynes and naphthyne and also with cyclooctyne that, following extrusion of dinitrogen, form isoxazole‐3‐propenoate derivatives in high yields and diastereocontrol. This practical method occurs at room temperature and provides a wide range of isoxazole‐based heterocycles with diverse functionality. 1,2‐Naphthyne, an unsymmetrical alkyne, forms only one regioisomeric product, exemplifying inherent regioselectivity. Although high, stereoselectivity is not 100 % in most cases, indicating that the loss of dinitrogen is stepwise. Derivative reactions of benzisoxazoles suggest their versatility. [ABSTRACT FROM AUTHOR]

Polysubstituted derivatives of pyrans, chromenes, and chromeno[2,3-b]pyridines incorporating a 4,5-dichloroisothiazole or 5-arylisoxazole-3-carbaldehyde fragment in the molecule were synthesized by successive and one-step three-component reactions of 4,5-dichloroisothiazole-3-carbaldehyde and 5-arylisoxazole-3-carbaldehyde with various 1,3-diketones, malononitrile or its dimer. The structure of the target products was proven by X-ray structural analysis. Notably, it was found that the planes of the azole and chromene rings in the molecules of (1,2-azol-3-yl)chromenes are almost perpendicular. Intrinsic antitumor activity and synergistic enhancement of the activity in combination with known cytostatics used in the therapy of oncological diseases were found for some of the synthesized compounds. [ABSTRACT FROM AUTHOR]

In this research, we conducted the synthesis of derivatives (2a-c) derived from 4-fluoro-3- methylacetophenone (FMAP) (1) using aldol condensation with substituteddibromobenzaldehydes (a-c). The condensation process occurred in ethanol with the presence of a base, leading to the creation of chalcone derivatives (2a-c). These chalcones serve as crucial intermediates for the production of a diverse array of heterocyclic products. Upon reaction with hydrazine, pyrazol derivatives (3a-c) were obtained, while the use of hydroxylamine hydrochloride resulted in the formation of isoxazole (4a-c). Additionally, the reaction with urea produced oxazine derivatives (5a-c). We characterized all these compounds using spectral techniques, monitoring their reactions through TLC and measuring melting points. Subsequently, we assessed the biological activity of these compounds against two distinct bacterial strains. [ABSTRACT FROM AUTHOR]

This work describes the synthesis, characterization, and in vitro and in silico evaluation of the biological activity of new functionalized isoxazole derivatives. The structures of all new compounds were analyzed by IR and NMR spectroscopy. The structures of 4c and 4f were further confirmed by single crystal X-ray and their compositions unambiguously determined by mass spectrometry (MS). The antibacterial effect of the isoxazoles was assessed in vitro against Escherichia coli, Bacillus subtilis, and Staphylococcusaureus bacterial strains. Isoxazole 4a showed significant activity against E. coli and B. subtilis compared to the reference antibiotic drugs while 4d and 4f also exhibited some antibacterial effects. The molecular docking results indicate that the synthesized compounds exhibit strong interactions with the target proteins. Specifically, 4a displayed a better affinity for E. coli, S. aureus, and B. subtilis in comparison to the reference drugs. The molecular dynamics simulations performed on 4a strongly support the stability of the ligand–receptor complex when interacting with the active sites of proteins from E. coli, S. aureus, and B. subtilis. Lastly, the results of the Absorption, Distribution, Metabolism, Excretion and Toxicity Analysis (ADME-Tox) reveal that the molecules have promising pharmacokinetic properties, suggesting favorable druglike properties and potential therapeutic agents. [ABSTRACT FROM AUTHOR]

Dearomative 1,3-dipolar cycloadditions of 1-Boc-pyrroles with in situ generated silver α-bromo alkylidenenitronates delivered a series of 3a,6a-dihydro-4-Boc-pyrrolo[2,3-d]isoxazole-2-oxides (17–91% yields) under very mild conditions. N-Deoxygenation of the cycloaddition product gave a dihydro-pyrrolo[2,3-d]isoxazole, elaborations of which produced various functionalized 2,3-dihydropyrroles and pyrrolidines, showcasing the potential utilities of our new strategy of pyrrole dearomatization. [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]

[Display omitted] The microwave-assisted cycloaddition of 2,6-disubstituted benzonitrile oxides to 1-iodobuta-1,3-diynes occurs at the iodo-substituted triple bond giving predominantly 5-alkynyl-4-iodo-1,2,3-isoxazoles. The Suzuki–Miyaura and Sonogashira cross-coupling reactions were used for the modification of the thus obtained 4-iodoisoxazoles. [ABSTRACT FROM AUTHOR]

The medicinal chemistry of ferrocene has gained its momentum after the discovery of biological activities of ferrocifen and ferroquine. These ferrocenyl drugs have been designed by replacing the aromatic moiety of the organic drugs, tamoxifen and chloroquine respectively, with a ferrocenyl unit. The promising biological activities of these ferrocenyl drugs have paved a path to explore the medicinal applications of several ferrocenyl conjugates. In these conjugates, the ferrocenyl moiety has played a vital role in enhancing or imparting the anticancer activity to the molecule. The ferrocenyl conjugates induce the cytotoxicity by generating reactive oxygen species and thereby damaging the DNA. In medicinal chemistry, the five membered nitrogen heterocycles (azoles) play a significant role due to their rigid ring structure and hydrogen bonding ability with the biomolecules. Several potent drug candidates with azole groups have been in use as chemotherapeutics. Considering the importance of ferrocenyl moiety and azole groups, several ferrocenyl azole conjugates have been synthesized and screened for their biological activities. Hence, in the view of a wide scope in the development of potent drugs based on ferrocenyl azole conjugates, herein we present the details of synthesis and the anticancer activities of ferrocenyl compounds bearing azole groups such as imidazole, triazoles, thiazole and isoxazoles. [ABSTRACT FROM AUTHOR]

Herein, the synthesis and biological evaluation of 6-fluoro-3-(piperidin-4-yl)benzo[d]isoxazole sulfonamide hybrids are discussed. All the synthesized molecules were assessed for anti-cancer and anti-TB activities using in vitro and in silico methods. The molecular docking study with CDK8 as a possible target for anti-cancer activity demonstrated that compounds 2, 3, 5, 7, 8, and 9 have a good binding affinity ranging from −8.7 to −10.3 kcal/mol against CDK8 (PDB 6T41) protein as compared with the standard drug 5-Fluorouracil (−5.0 kcal/mol). The in vitro anti-mycobacterial screening reveals that compounds 2 and 3 elicited moderate anti-TB activity with a MIC value of 25 µM. Compounds 2 and 3 exhibited moderate in vitro anti-proliferative potency against the cancer cell lines MCF-7 and HCT-116. Moreover, compound 3 exhibited a better anti-oxidant effect among all tested compounds. Some quantum chemical parameters and drug-likeness profiling of the molecules were modeled by density functional theory (DFT) and ADME studies. The obtained theoretical results are in good agreement with the experimental results. [ABSTRACT FROM AUTHOR]

By modifying ring A in the dammarane triterpenoid dipterocarpol, derivatives with isoxazole and 2-cyano-1-ene fragments were synthesized, which showed activity against the influenza A virus (H1N1) with selectivity indices of 19 and 23. [ABSTRACT FROM AUTHOR]

Meso‐nitrile oxide group in 1,7‐Diphenyl‐containing BODIPYs can be involved in highly unusual [3+2] intramolecular cycloaddition reaction with the formation of the dihydrobenzo[d]isoxazole‐containing BODIPYs. Oxidation of these compounds results in the formation of unprecedented either benzisoxazole‐ or benzo[b]azepine‐fused fully conjugated NIR absorbing BODIPYs. The photophysical properties and electronic structures of the target compounds were studied by an array of experimental and theoretical methods. [ABSTRACT FROM AUTHOR]

Reactive open-shell ring systems comprising C, N, O, and S atoms are crucial for the radiation-induced molecular evolution and relevant to life and interstellar regions. Herein, we targeted the dehydro radical isomers derived from five-membered heterocycles pyrazole 1, isothiazole 2, and isoxazole 3. Using electronic structure and unimolecular decomposition-based mechanistic calculations, we attempted to envisage the variables influencing the thermodynamic and kinetic stability of radical isomers 1a–1d, 2b–2d and 3b–3d. Evidence suggests that the factors including (hetero)aromaticity, the radical electron's role in delocalization (resonance), and the ring strain play a significant role. The N-centered pyrazole radical 1a was found to be entirely delocalised, which impacts its higher thermodynamic and kinetic stability. Conversely, the C-centered radicals (1b–1d, 2b–2d, and 3b–3d) show important contributions from the interaction between the radicals and lone pair electrons, evident from the NBO analysis. The mechanistic studies through unimolecular decomposition channels show the importance of ring-opening channels as the decisive factor in their kinetic stability. Preferential cleavage of X–N or C–X bonds and formation of fragmented products like acetylene, HCN, HNC, CO, CS, NHCCH radicals, SCCH radicals, OCCH radicals, HNNC radicals, SNC radicals, and ONC radicals were also characterized. [ABSTRACT FROM AUTHOR]

This article discusses a catalytic strategy for the conversion of isoxazoles and oxadiazoles into pyrazoles and 1,2,4-triazoles, respectively, through a formal O-to-N exchange. The protocol utilizes catalytic amounts of an air-stable Ni(4-CF3 stb) 3 complex in combination with hydrazine. The authors demonstrate the generality of the protocol and its functional group tolerance. This research provides a potential solution for the rapid evaluation of five-membered heterocyclic scaffolds in synthetic campaigns. [Extracted from the article]

A facile synthesis of novel 5-hydroxy-6,6-dimethyl-6,7-dihydrobenzo[d]isoxazol-4(5H)-ones and 5-hydroxy-6,6-dimethyl-6,7-dihydrobenzo[c]isoxazol-4(5H)-ones starting from the corresponding 6,6-dimethyl-6,7-dihydrobenzisoxazol-4(5H)-ones was developed. The approach includes an oxidation of methylene group adjacent to carbonyl to ketone with selenium dioxide in acetic acid followed by regioselective reduction of the formed carbonyl to hydroxyl group with triethyl silane in trifluoroacetic acid. A series of 14 target compounds were prepared using developed method with yield of 50–87% in two steps. The synthesized α-hydroxy ketones were tested as potential antiproliferative agents against BT-474 breast carcinoma cell line, however at concentration of 50 µM they showed no negative effect on the growth of these cancer cells. [ABSTRACT FROM AUTHOR]

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 work, we developed an effective protocol for the synthesis of a series of novel 6-amino-4-substituted-pyrano[3,2-d]isoxazole-5-carbonitrile derivatives via one-pot multicomponent reaction of aromatic aldehyde, malononitrile and 3-phenyl-5-isoxazolone in aqueous ethanol using L-proline as a catalyst. The structures of the compounds were confirmed by using analytical and spectroscopic techniques. Further, the obtained compounds were screened for anti-diabetic, cytotoxicity and in silico docking studies. Anti-diabetic activity was done by a-amylase and a-glucosidase assay and cytotoxicity was done by MTT assay. The activity results revealed that most of the analogs exhibited good efficiency when compared with the standards, acarbose and doxorubicin, respectively. The in silico docking study suggested that all the obtained compounds effectively interacted with exo-β-D-glucosaminidase and P38 MAP kinase proteins. Additionally, the compounds were subjected to in silico ADME studies, which suggested that the compounds met all five requirements with good bioavailability; thus, these compounds can be used as pharmaceutical agents. [ABSTRACT FROM AUTHOR]

Context: In the present work, the influence of aromatic ring substitution on a series of small-donor organic molecules (A, B, C, D, and E) with isoxazole cores was investigated for photovoltaic applications in organic solar cells. Frontier molecular orbital analysis, chemical reactivity descriptors, dipole moment, and population analysis showed that all the organic materials have intramolecular charge transfer abilities capable of donating electrons to the acceptor material (PCBM). The required photovoltaic parameters such as Voc, FF, Jsc, LHE, and other associated optoelectronic parameters are reported. The results demonstrate that aromatic ring substitution influences charge transfer and power conversion efficiencies of solar cells. That is, an increase in the aromatic character of a material increases its charge transfer, and as a result, its photovoltaic properties are increased. Additionally, all the investigated derivatives are good charge transporters with suitable electron reorganization energies, which are beneficial for minimizing energy loss. Hence, these organic derivatives with isoxazole backbones are promising materials and may provide fresh insights into the design of new materials for organic solar cell applications. Method: All calculations were performed using DFT and the ORCA 4.1.0 program package as the main tool for geometry optimization and frequency calculations. The Avogadro 1.2.1 visualization tool was used to prepare all input files executed by ORCA 4.1.0. The BP86, B3LYP, and wB97M series of functionals coupled with the def2/TZVP basis set were employed for geometry optimization. All energy-related calculations were carried out using the M06-2x functional. Multiwfn version 3.7 was used for aromaticity and population analysis. Excited state and UV-visible spectra were simulated using the TD-DFT method at the CAM-B3LYP-D3, wB97X-D3, and PBE0-D3 coupled with the ma-def2-TZVP basis set. Moreover, solvent effects were incorporated using the SMD scheme as incorporated in the ORCA software. Lastly, the RIJCOSX approximations were used to speed up calculations while maintaining accuracy. [ABSTRACT FROM AUTHOR]

The previously unknown cyclopropane spiro-fused with isoxazol-5-one ((1RS,3SR)-1-(4-methylbenzyl)-7-phenyl-5-oxa-6-azaspiro[2.4]hept-6-en-4-one) was synthesized from benzylideneisoxazol-5-one in 34% yield via double methylene transfer from diazomethane. The structure of the compound was established based on 1H, 13C, and 2D NMR spectroscopy and high-resolution mass spectrometry, and confirmed by X-ray diffraction analysis. [ABSTRACT FROM AUTHOR]

A new mode of reactivity of N‐sulfonylhydrazones towards alkynes is described: ketone‐derived N‐tosylhydrazones (NTHs) bearing α‐H atoms behave as [NN] synthons in their reactions with alkoxy alkynyl Fischer carbene complexes (FCCs) and only the two N atoms are incorporated into the newly formed pyrazole ring. The scope of the reaction, leading to 5‐methoxy‐N‐alkenyl pyrazoles, proved to be wide regarding both partners; thus, a variety of aryl and primary, secondary, and tertiary alkyl substituents are tolerated within the FCC, while aryl alkyl NTHs, symmetric and asymmetric dialkyl NTHs and NTHs derived of cyclic ketones can be also employed. In addition, the reaction can be performed at large scale and applied for late‐stage diversification of natural products. A reasonable reaction mechanism is also proposed, which is supported by deuteration experiments and DFT calculations. [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]

A new series of compounds, namely 2-{[4'-(3"-aryl)-2"-propene-1"-one-phenyl]amino}benzoic acids (3a-3j) and 2-{[4'-(5"-aryl)isoxazol-3"-yl]phenyl amino} benzoic acids (4a-4j), were synthesized. The structures of these compounds were confirmed by 1H NMR, IR, Mass spectral analysis. The compounds (3a-3j) and (4a-4j) have been evaluated their antimicrobial activity. [ABSTRACT FROM AUTHOR]

In our previous work, we have synthesised novel isoxazole conjugated pyrazoline derivatives by reacting isoxazolyl chalcones (1-15) with thiosemicarbazide in glacial acetic acid. From these compounds, 15 isoxazole conjugated pyrazoline carbothioamides were synthesised, compounds 24 and 25 are selected for further optimisation. In continuation to this work, pyrazoline-clubbed thiazole hybrids were synthesied by using potential antimycobacterial isoxazole conjugated pyrazoline carbothioamides - 24 and 25. The pyrazoline-1-carbothioamides-24 (3-(isoxazol-5-yl)-5-(3,5-dimethoxyphenyl)- 4,5-dihydro-1H-pyrazole-1-carbothioamide) and 25 (3-(isoxazol-5-yl)-5-(2,3,4-trimethoxyphenyl)- 4,5-dihydro-1H-pyrazole-1-carbothioamide) were further optimized and synthesized eight more compounds (24a-24d, 25a-25d) which have a substituted thiazole ring. These compounds are purified by recrystallisation and charecterised by FT IR, 1H NMR and Mass spectra. Compound 24a have shown potent antimycobacterial activity. [ABSTRACT FROM AUTHOR]

Easy-to-handle N-hydroxyacridinecarbimidoyl chloride hydrochlorides were synthesized as convenient nitrile oxide precursors in the preparation of 3-(acridin-9/2-yl)isoxazole derivatives via 1,3-dipolar cycloaddition with terminal alkynes, 1,1-dichloroethene, and acrylonitrile. Azirines with an acridin-9/2-yl substituent attached directly or via the 1,2,3-triazole linker to the azirine C2 were also synthesized. The three-membered rings of the acridine–azirine hybrids were found to be resistant to irradiation in the UV/visible boundary region, despite their long-wave absorption at 320–420 nm, indicating that the acridine moiety cannot be used as an antenna to transfer light energy to generate nitrile ylides from azirines for photoclick cycloaddition. The acridine–isoxazole hybrids linked at the C9–C3 or C2–C3 atoms under blue light irradiation underwent the addition of such hydrogen donor solvents, such as, toluene, o-xylene, mesitylene, 4-chlorotoluene, THF, 1,4-dioxane, or methyl tert-butyl ether (MTBE), to the acridine system to give the corresponding 9-substituted acridanes in good yields. The synthesized acridine–azirine, acridine–isoxazole, and acridane–isoxazole hybrids exhibited cytotoxicity toward both all tested cancer cell lines (HCT 116, MCF7, and A704) and normal cells (WI-26 VA4). [ABSTRACT FROM AUTHOR]

The reaction of nitrile oxides with 2,3‐dichloroprop‐1‐ene, 1,3‐dichloroprop‐1‐ene, and 1,3‐dichlorobut‐2‐ene leads to 5‐(chloromethyl)isoxazoles, 4‐(chloromethyl)isoxazoles, or to mixtures of both regioisomers. The direction of cycloaddition and reactivity of substrate is determined by the steric hindrance at the terminal carbon atom of the alkene double bond. It has been found that the isomeric products of cycloaddition of nitrile oxides to 1,3‐dichloropropene have significantly different dehydrochlorination capabilities. The experimental data on the regioselectivity of cycloaddition and the relative reactivity of substrates are in agreement with the results of quantum chemical calculations. [ABSTRACT FROM AUTHOR]

The reaction of 1-(3-(furan-2-yl)-5-methyl-1-(4-nitrophenyl)-1H-pyrazol-4-yl)ethan-1-one 1 with dimethylformamide dimethyl acetal (DMF-DMA) afforded 3-(dimethylamino)-1-(3-(furan-2-yl)-5-methyl-1-(4-nitrophenyl)-1H-pyrazol-4-yl)prop-2-en-1-one 2. Then the treatment of enaminone 2 with the appropriate hydrazonoyl halides 3a–f in chloroform in the presence of triethylamine at reflux gave novel bipyrazolyl methanone derivatives 4a–f. The novel bipyrazole derivatives 4a–c and 4d–f reacted with hydrazine hydrate in ethanol at reflux to give the corresponding pyrazolopyridazinones 9a–c and pyrazolopyridazines 10d–f, respectively. Stirring of hydroximoyl chlorides 11a,b with enaminone 2 in chloroform in the presence of triethylamine at room temperature afforded isoxazole derivatives 12a,b. The reaction of isoxazoles 12a,b with hydrazine hydrate in refluxing ethanol gave the corresponding isoxazolopyridazines 14a,b. [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]

An effective approach to 5‐triazolyl‐substituted 6,7‐dihydrobenzo[d]isoxazol‐4(5H)‐ones and 4,5,6,7‐tetrahydrobenzo[d]isoxazoles was developed. The approach included α‐keto bromination of 6,7‐dihydrobenzo[d]isoxazol‐4(5H)‐one followed by nucleophilic substitution of bromine with the azide group. For the preparation of 5‐azido‐6,7‐dihydrobenzo[d]isoxazol‐4(5H)‐one, the carbonyl group at position 4 was reduced to a methylene group under ionic hydrogenation conditions using triethylsilane as a reducing agent. Cu(I)‐catalyzed [2+3] cycloaddition of terminal alkynes to both obtained azides was used for the synthesis of two series of triazolyl derivatives. Compounds, which contain in their structures common for some Hsp90 inhibitors 2,4‐dihydroxy‐5‐isopropylphenyl fragment, were evaluated as antiproliferative agents against two breast cancer cell lines: hormone‐dependent MCF7 and HER2‐positive HCC1954. The lead compound showed half‐maximal inhibitory concentration (IC50) values below 5 μM and induced significant changes in the Hsp90 signaling pathways in HER2‐positive HCC1954 cells. It increased the expression of Hsp70 (used as a pharmacodynamic marker of Hsp90 inhibition) and inhibited the expression of HER2, p‐c‐Met, c‐Met, and p‐AKT. The combination of the selected isoxazole‐triazole hybrid molecule and the earlier described apoptosis inducer LCTA‐3344 demonstrated a significant antiproliferative effect against HCC1954 cells. The lead compound was revealed to be a promising candidate for future anticancer drug design, particularly against aggressive breast cancer positive for HER2. [ABSTRACT FROM AUTHOR]

2H‐arizines are important three‐membered heterocycles in organic chemistry. Recently, many advances in the synthesis and functionalization of 2H‐arizines have been reported. Neber rearrangement, isomerization of isoxazole, oxidation of enamine, C−H bond activation, decomposition of vinyl azide, functionalization of alkyne, and multi‐step synthesis have been developed for the efficient assembly of 2H‐azirines. As versatile and highly strained three‐membered unsaturated heterocycles, 2H‐azirines can be used as distinctive building blocks towards significant functional groups, and have attracted extensive attention for the fabrication of numerous heterocycles. Recent studies have focused on [3+n] ring‐expansion reactions, nucleophilic addition of C=N double bond or continuous nucleophilic addition followed by cyclization, ring‐opening of 2H‐azirines to acyclic compounds, and substitution of sp3‐C−H of 2H‐azirines. One of the most critical challenges is seeking for a selective opening of the specific three bonds of the strained azirine circle, some of what can be achieved on the basis of metal catalyst, photocatalysis, or combination of metal catalyst and photocatalysis. In this review, recent advances involving the synthesis and reactivity of 2H‐arizines accompanied with challenges and breakthroughs are summarized. The review mainly covers the period from 2019 to 2023. [ABSTRACT FROM AUTHOR]

A practical metal-free and additive-free approach for the synthesis of 6/7/8-membered oxacyclic ketone-fused isoxazoles/isoxazolines tetracyclic or tricyclic structures is reported through Csp3–H bond radical nitrile oxidation and the intramolecular cycloaddition of alkenyl/alkynyl-substituted aryl methyl ketones. This convenient approach enables the simultaneous formation of isoxazole/isoxazoline and 6/7/8-membered oxacyclic ketones to form polycyclic architectures by using tert-butyl nitrite (TBN) as a non-metallic radical initiator and N–O fragment donor. [ABSTRACT FROM AUTHOR]

A palladium‐catalyzed cascade cyclization/alkenylation for the assembly of synthetically valuable isoxazolyl vinylsilane derivative has been accomplished. Easily accessible ynone oximes, and available vinylsilane agents were used as the reaction starting materials This protocol features broad substrate scope, good functional group tolerance, and good step‐ and atom‐economy. Remarkably, this approach provides a new approach for the construction of structurally diverse isoxazolyl‐containing vinylsilanes with high molecular complexity, showing a promising application in synthetic and pharmaceutical chemistry. [ABSTRACT FROM AUTHOR]

A series of substituted ethyl 5-phenyl-1,2-oxazole-3-carboxylates were synthesized in good to excellent yields in one step using hydroxylamine base and ethyl 2,4-dioxo-4-(4-R-phenyl)butanoates bearing both electron-donating and electron-withdrawing moieties on the benzene ring, and antioxidant properties of the products were investigated by the DPPH method. The proposed method is suitable for the large-scale production of isoxazole derivatives. [ABSTRACT FROM AUTHOR]

In this paper, we report the synthesis of quinoxaline‐isoxazole‐piperazine conjugates. The anticancer activity was evaluated against three human cancer cell lines, including MCF‐7 (breast), HepG‐2 (liver), and HCT‐116 (colorectal). The outcomes of the tested compounds 5d, 5e, and 5f have shown more potent activity when compared to the standard drug erlotinib. In a cell survivability test (MCF‐10A), three potent compounds (5d, 5e, and 5f) were evaluated against the normal breast cell line, although neither of them displayed any significant cytotoxicity with IC50 values greater than 84 μM. Furthermore, the compounds 5d, 5e, and 5f were tested for tyrosine kinase EGFR inhibitory action using erlotinib as the reference drug and compound 5e was shown to be more potent in inhibiting the tyrosine kinase EGFR than sorafenib. In addition to this, molecular docking studies of compounds 5d, 5e, and 5f demonstrated that these compounds had more EGFR‐binding interactions. The potent compounds 5d, 5e, and 5f were subjected to in silico pharmacokinetic assessment by SWISS, ADME, and pkCSM. While the compounds 5d, 5e, and 5f followed Lipinski, Veber, Egan, and Muegge rules without any deviation. [ABSTRACT FROM AUTHOR]