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A simple one-pot and catalyst-free method is reported for synthesis of some new bipyrazole derivatives by three-component reaction between arylglyoxals, 3-methyl-1H-pyrazol-4(5H)-one and aroylphenylhydrazone derivatives. The reactions were carried out in ethanol as a green solvent in neutral reaction conditions and products were simply isolated by filtering of the precipitated solids in high yields. All products were characterized by their 1H and 13C NMR and IR spectral and elemental analysis data. [ABSTRACT FROM AUTHOR]

Highly selective fluorescence "turn on" probes (PTSC and TSC) based on a conjugate of pyrazolone and thiosemicarbazide were devised and synthesized. The structure was verified by 1H NMR, 13C NMR and HR-MS. The probe demonstrated effectiveness, high selectivity, and specificity to capture indium ions. The fluorescence intensity of the probe solution was significantly enhanced by the addition of In3+. The 1 : 1 complexation between In3+ and probe PTSC was confirmed by Job's plot, and the limit of detection (LOD) of PTSC for In3+ was calculated to be 2.01 × 10−7 M. Furthermore, PTSC was produced as test strips, which have enormous potential to detect In3+ ions in the environment. [ABSTRACT FROM AUTHOR]

Highly selective fluorescence "turn on" probes (PTSC and TSC) based on a conjugate of pyrazolone and thiosemicarbazide were devised and synthesized. The structure was verified by 1H NMR, 13C NMR and HR-MS. The probe demonstrated effectiveness, high selectivity, and specificity to capture indium ions. The fluorescence intensity of the probe solution was significantly enhanced by the addition of In3+. The 1 : 1 complexation between In3+ and probe PTSC was confirmed by Job's plot, and the limit of detection (LOD) of PTSC for In3+ was calculated to be 2.01 × 10−7 M. Furthermore, PTSC was produced as test strips, which have enormous potential to detect In3+ ions in the environment. [ABSTRACT FROM AUTHOR]

We disclose a photoredox-catalyzed arylative radical cascade between N′-arylidene-N-acryloylhydrazides and diaryliodonium reagents to obtain the corresponding benzylated pyrazolones in good yields. The protocol was extended to three-component coupling involving the 1,4-diazabicyclo[2.2.2]octane bis(sulfur dioxide) (DABSO) adduct as a sulfur dioxide surrogate for the synthesis of arylsulfonylated pyrazolones. Both reactions exhibit broad scope, scalability, and high functional group tolerance. [ABSTRACT FROM AUTHOR]

A green and efficient synthesis of alkyl 2-((5-hydroxy-1H-pyrazole-4-carbonothioyl)thio)acetates is described. The method involves a one-pot, solvent-free reaction of pyrazolone derivatives, carbon disulfide, and alkyl bromoacetates in the presence of triethylamine. The crude products were readily purified by simple water washing followed by recrystallization from diethyl ether. The structures of the synthesized pyrazole-4-carbonothioyl-thio-acetate derivatives were confirmed by IR, 1H NMR, 13C NMR, and mass spectrometry. [ABSTRACT FROM AUTHOR]

Isochroman is one of the powerful scaffolds which demonstrated various important biologically activities. Herein we represented the novel and versatile method for the synthesis of valuable isochroman spiropyrazolones of difunctional peroxides and pyrazolones via [1+5] annulation. This process represents a novel spiroisochroman synthesis protocol and is featured by good functional group compatibility, mild conditions and readily available substrates. [ABSTRACT FROM AUTHOR]

A mechanochemical cross‐dehydrogenative coupling reaction of pyrazolones with thiols using ball milling is described. Benzeneselenol and dichalcogenide substrates are also compatible under mild reaction conditions, yielding up to 99 %. Notable features of this reaction include its metal‐ and solvent‐free, wide substrate scope and good functional group tolerance. Preliminary mechanistic investigations suggest that a radical pathway is likely involved in this C−H chalcogenation reaction. [ABSTRACT FROM AUTHOR]

In this study, we successfully synthesized a pyrazole derivative, specifically 4-phenylpiperidin-4-ol substituted pyrazole (CHP), through the reaction of Grignard reagents in combination with pyrazole. This newly synthesized molecule was subjected to a comprehensive evaluation for both its photophysical and biological applications. Notably, CHP exhibited promising invitro antifungal and antibacterial activities, primarily attributed to the presence of the 4-phenylpiperidin-4-ol moiety and resulting component contributed to an enhanced absorption rate of lipids, thereby improving the pharmacological activity of CHP. This correlation between structure and function was further supported by the outcomes of structure-activity relationship studies. Additionally, we conducted in silico studies to examine the molecular interactions of the synthesized molecule with key proteins, including DNA Gyrase, Lanosterol 14 α-demethylase, and KEAP1-NRF2. The results unveiled robust binding interactions at specific sites within these proteins, indicating potential therapeutic relevance. Furthermore, the photophysical properties of the synthesized compounds were thoroughly investigated using the ab-initio technique. This involved the determination of ground state optimization and HOMO-LUMO energy levels, all calculated with the DFT-B3LYP-6-31G(d) basis set. The assessment of the theoretically estimated HOMO-LUMO value provided insights into the global chemical reactivity descriptors, revealing that the synthesized molecule boasts a highly electronegative and electrophilic index. Taken together, our findings suggest that pyrazole derivatives with 4-phenylpiperidin-4-ol substitutions exhibit promising applications in both photophysical and biological contexts.

The development of methods for the selective acylative kinetic resolution (KR) of tertiary alcohols is a recognised synthetic challenge with relatively few successful substrate classes reported to date. In this manuscript, a highly enantioselective isothiourea‐catalysed acylative KR of tertiary pyrazolone alcohols is reported. The scope and limitations of this methodology have been developed, with high selectivity observed across a broad range of substrate derivatives incorporating varying substitution at N(2)‐, C(4)‐ and C(5)‐, as well as bicyclic constraints within the pyrazolone scaffold (30 examples, selectivity factors (s) typically >100) at generally low catalyst loadings (1 mol %). The application of this KR method to tertiary alcohols derived directly from a natural product (geraniol), alongside pharmaceutically relevant drug compounds (indomethacin, gemfibrozil and probenecid), with high efficiency (s >100) is also described. The KR process is readily amenable to scale up using bench grade solvents and reagents, with effective resolution on a 50 g (0.22 mol) scale demonstrated. The key structural motif leading to excellent selectivity in this KR process has been probed through computation, with an NC=O⋅⋅⋅isothiouronium interaction from substrate to acylated catalyst observed within the favoured transition state. Similarly, the effect of C(5)‐aryl substitution that leads to reduced experimental selectivity is probed, with a competitive π–isothiouronium interaction identified as leading to reduced selectivity. [ABSTRACT FROM AUTHOR]

We report sequential wavelength‐selective photochemical transformations of 1‐alkenylpyrazolo[1,2‐a]pyrazolones to pyrazolo[1,2‐a][1,2]diazepines or cyclobuta[c]pyrazolo[1,2‐a]pyrazolones. Irradiation of 1‐alkenylpyrazolo[1,2‐a]pyrazolones with visible‐light (blue LED, 457 nm) induced selective 'ring switching' transformation into pyrazolo[1,2‐a][1,2]diazepines, which underwent electrocyclisation yielding cyclobuta[c]pyrazolo[1,2‐a]pyrazolones upon irradiation with UV−A light (black LED, 365 nm). Due to the very narrow irradiation wavelength now available from OLED sources, the selective formation of either 5,7‐bicyclic or 5,5,4‐tricyclic ring systems from the 5,5‐bicyclic starting material is possible by changing the wavelength of the irradiation source. The transformations took place under mild conditions in the absence of additives or photocatalysts. Mechanistic studies indicate that these transformations proceed through the formation of an excited triplet state of the substrate, followed by selective homolytic C(1)−N(8) bond cleavage, intersystem crossing, and cyclization of the zwitterionic intermediate on the ground potential energy surface. The subsequent photoinduced disrotatory stereospecific 4π‐electrocyclization of the 5,7‐bicyclic systems leads to 3D‐rich 5,5,4‐tricyclic products. [ABSTRACT FROM AUTHOR]

A highly selective fluorescent "turn on" probe for Al3+ based on the conjugate of aminourea and pyrazolone was devised and synthesized. The fluorescence intensity of the probe solution was significantly enhanced by the addition of Al3+ to the probe solution. Other cations such as Cu2+, Ni2+, Fe3+, Co2+, Ag+, Mn2+, Sn2+, Sn4+, Mg2+, Li+, Zn2+, Zr4+, Ce3+, Ca2+, and Na+ did not interfere the detection of Al3+. The 1 : 1 complexation between Al3+ and the probe was confirmed by Job's plot curve. In addition, the solution of the complex formed by Al3+ and the probe can be used for the specific detection of Hg2+, appearing as fluorescence quenching. [ABSTRACT FROM AUTHOR]

A photoinduced Wolff rearrangement/chiral isothiourea catalyzed [4+2] cycloaddition reaction of pyrazolone derivatives and α‐diazoketones was developed, affording the corresponding dihydropyrano[2,3‐c]pyrazolone derivatives in moderate to good yields (50–94 %) with satisfactory to excellent diastereoselectivities (>20 : 1 dr, in almost all cases) and enantioselectivities of 31–99 %. This protocol features readily available substrates, mild reaction conditions, and effective construction of vicinal tertiary and quaternary carbon stereocenters. [ABSTRACT FROM AUTHOR]

In this study, we present a convenient synthesis of spiro-pyrazolone–pyrrolidinones via NaH-mediated cascade ipso-cyclization of unsaturated pyrazolones with 2-chloro-N-phenylacetamides. This method offers an efficient route to a variety of highly functionalized spiro-pyrazolone–pyrrolidinones with good yields under transition metal-free conditions. This protocol features several advantages, including stable substrates, straightforward operational procedures, and both atom and step economy. Notably, the practical feasibility of this strategy has been demonstrated on a gram scale, yielding good product quantities. [ABSTRACT FROM AUTHOR]

A one-pot multicomponent approach towards a hybrid heterocyclic pyrano[2,3-c]pyrazole-pyrazolone framework involving tandem Knoevenagel condensation, sequential intermolecular 1,6-Michael addition, and 6-endo dig cyclization between diynones and pyrazolones, mediated by DBU, has been discovered. This process embodies several green and sustainable chemistry features. Preliminary bioactivity profiling of the new chemical entities indicates neuroprotective and AChE inhibitory activities. [ABSTRACT FROM AUTHOR]

An environmentally friendly, versatile multicomponent reaction for synthesizing isoxazol-5-one and pyrazol-3-one derivatives has been developed, utilizing a freshly prepared g-C3N4·OH nanocomposite as a highly efficient catalyst at room temperature in aqueous environment. This innovative approach yielded all the desired products with exceptionally high yields and concise reaction durations. The catalyst was well characterized by FT-IR, XRD, SEM, EDAX, and TGA/DTA studies. Notably, the catalyst demonstrated outstanding recyclability, maintaining its catalytic efficacy over six consecutive cycles without any loss. The sustainability of this methodology was assessed through various eco-friendly parameters, including E-factor and eco-score, confirming its viability as a green synthetic route in organic chemistry. Additionally, the gram-scale synthesis verifies its potential for industrial applications. The ten synthesized compounds were also analyzed via a PASS online tool to check their several pharmacological activities. The study is complemented by in silico molecular docking, pharmacokinetics, and molecular dynamics simulation studies. These studies discover 5D as a potential candidate for drug development, supported by its favorable drug-like properties, ADMET studies, docking interaction, and stable behavior in the protein binding cavity. [ABSTRACT FROM AUTHOR]

Metamizole, or dipyrone, has been used for decades as a non-narcotic analgesic, providing pain relief from musculoskeletal disorders and antipyretic and antispasmolytic properties. Despite being in use since the 1920s, its mechanism of action still needs to be discovered. Despite causing fewer adverse effects when compared to other analgesics, its harmful effects on the blood and lack of evidence regarding its teratogenicity make the usage of the drug questionable, which has led to it being removed from the drug market of various countries. This narrative review aims to provide a detailed insight into the mechanism of action and efficacy, comparing its effectiveness and safety with other classes of drugs and the safety profile of metamizole. [ABSTRACT FROM AUTHOR]

A series of benzoquinoline-employing heterocycles was synthesized by treating 3-chlorobenzo[f]quinoline-2-carbaldehyde with N-phenyl-3-methylpyrazolone, 4-aminoacetophenone, 1,2-diaminoethane, and 2-cyanoethanohydrazide. Also, pyridine, chromene, α,β-unsaturated nitrile, thiosemicarbazone, and 1,2-bis-aryl hydrazine derivatives were prepared from the cyanoethanohydrazone obtained. The DFT calculations and experiment outcomes were consistent. In vitro screening of their antiproliferative efficacy was examined against HCT116 and MCF7 cancer cell lines. The pyrazolone 2 and cyanoethanohydrazone 5 derivatives exhibited the most potency, which was demonstrated by their molecular docking towards the CDK-5 enzyme. The binding energies of compounds 2 and 5 were − 6.6320 kcal/mol (with RMSD of 0.9477 Å) and − 6.5696 kcal/mol (with RMSD of 1.4889 Å), respectively, which were near to that of co-crystallized ligand (EFP). This implies a notably strong binding affinity towards the CDK-5 enzyme. Thus, pyrazolone derivative 2 would be considered a promising candidate for further optimization to develop new chemotherapeutic agents. In addition, the ADME (absorption, distribution, metabolism, and excretion) analyses displayed its desirable drug-likeness and oral bioavailability properties. [ABSTRACT FROM AUTHOR]

In the present work, the aryl-substituted pyrazolone derivative ethyl 3-((3-methyl-1-phenyl-1H-pyrazol-5-yl)oxy)-2-methyleneheptanoate (ETT) has been synthesized by the reaction of Baylis-Hillman acetate with pyrazolones and screened for their in vitro antifungal, antibacterial, and antioxidant properties. The molecule shows good in vitro antifungal and antibacterial activities due to the presence of pentane, which enhances the absorption rate by its increased lipid solubility and improves the pharmacological activity. It is also evident from the results obtained from structure-activity relationship (SAR) studies. In silico studies were conducted on the synthesized molecule, examining its interactions with DNA Gyrase, Lanosterol14 alpha demethylase, and KEAP1-NRF2 proteins. The results revealed strong binding interactions at specific sites. Further, the photophysical properties of synthesized compounds were theoretically estimated using the ab-intio technique. The ground state optimization, dipole moment, and HOMO–LUMO energy levels are calculated using the DFT-B3LYP-6-31G(d) basis set. Using the theoretically estimated HOMO–LUMO value, global chemical reactivity descriptor parameters are estimated, and the result shows the synthesised molecule has a highly electronegative and electrophilic index. NBO analysis proved the presence of intermolecular ON.H hydrogen bonds caused by the interaction of the lone pair of oxygen with the anti-bonding orbital. The results suggest that pentane-substituted pyrazolone derivatives show good photophysical and biological applications. [ABSTRACT FROM AUTHOR]

In this study, a highly effective microwave‐assisted method employing a multicomponent domino Knoevenagel/phospha‐Michael reaction has been established. This approach facilitates the synthesis of a novel set of pyrazolylphosphonate derivatives in good yields by combining aryl aldehydes with pyrazolones and trialkylphosphites, utilizing piperidine as a Bronsted base catalyst. All pyrazolylphosphonates have been characterized by means of IR, 1H‐NMR, 13C‐NMR, and HRMS analyses and physical methods. This protocol can be characterized by its eco‐friendly nature, exceptional efficiency in terms of product yields, and short reaction times. [ABSTRACT FROM AUTHOR]

Initially, a new organometallic catalyst with nano-silica gel substrate and Ni active center, namely nano-SiO2@nPr@DPyE-Ni was produced, and its properties were thoroughly debated. It was then applied with excellent performance to produce symmetric di-aryl sulfides (14 entries, 78–98%, 20–150 min, EtOH, and 70 °C), and 2-aryl-5-methyl-2,3-dihydro-1H-3-pyrazolones (12 entries, 91–98%, 2–4 min, solvent-free, and r.t). In both production routes, the nanocatalyst was recyclable and reusable for more than seven runs, and its heterogeneous nature was checked and confirmed through the recycling results, hot filtration test, and ICP-OES (coupled plasma optical emission spectroscopy) method. [ABSTRACT FROM AUTHOR]

A catalytic asymmetric (3+2) cyclization of pyrazolone‐based MBH adducts with alkylidenyl isoxazolones was presented by using DMAP‐derived chiral catalyst, affording bis‐spirocyclic pyrazolones bearing vicinal all‐carbon quaternary stereocenters within an imbedded cyclopentene ring scaffold in good yields with excellent stereoselectivities under mild conditions. [ABSTRACT FROM AUTHOR]

A new method to generate a series of spiro-pyrazolone-tetrahydrofurans/pyrans is developed by using a base-mediated cascade ipso-cyclization of unsaturated pyrazolones and haloalcohols. Noteworthy aspects of this methodology include its brief reaction duration, expansive substrate applicability, very good yields, and mild reaction conditions without the need for transition metals. Interestingly, the practical feasibility of the present strategy is also investigated in gram scales that provided good yields of the products. [ABSTRACT FROM AUTHOR]

The goal of this study was directed to synthesize a novel class of annulated compounds containing difuro[3,2-c:3′,2′-g]chromene. Friedländer condensation of o-aminoacetyl derivative 3 was performed with some active methylene ketones, namely, 1,3-cyclohexanediones, pyrazolones, 1,3-thiazolidinones and barbituric acids, furnished furochromenofuroquinolines (4,5), furochromenofuropyrazolopyridines (6–8), furochromenofurothiazolopyridines (9,10) and furochromenofuropyridopyrimidines (11, 12), respectively. Also, condensation of substrate 3 with 5-amine-3-methyl-1H-pyrazole and 6-amino-1,3-dimethyluracil, as cyclic enamines, resulted in polyfused systems 13 and 14, respectively. In vitro antimicrobial efficiency of the prepared heterocycles against microbial strains exhibited variable inhibition action, where compound 3 was the most effective against all kinds of microorganisms. A significant cytotoxic activity was seen upon the annulation of the starting compound with thiazolopyridine (9 and 10) as well as pyridopyrimidine moieties (11, 12 and 14). The spectroscopic and analytical results were used to infer the structures of the novel synthesized compounds. [ABSTRACT FROM AUTHOR]

Pyrazolone moiety bearing an all‐carbon quaternary stereogenic center is frequent in biologically active products and pharmaceuticals. The catalytic route for the construction of quaternary carbon centers poses a formidable challenge. In this report, catalytic asymmetric Michael addition of 4‐monosubstituted‐pyrazol‐5‐ones to simple enones catalyzed by primary amine‐Brønsted acid composite has been developed. An array of pyrazolone derivatives bearing vicinal all carbon quaternary and tertiary stereocenters, were obtained in moderate to good diastereoselectivities (up to 92 : 8 dr) and good to excellent enantiomeric excess (up to 99 % ee). In addition, antipode for enantiomers of the pyrazolone derivatives were also realized in good to high stereoselectivities (up to 92 : 8 dr and up to 98 % ee). [ABSTRACT FROM AUTHOR]

Discovered in the 19th century, ethyl acetoacetate has been central to the development of organic chemistry, including its pedagogy and applications. In this study, we present borylated derivatives of this venerable molecule. A boron handle has been installed at either α ${{\rm \alpha }}$ ‐ or β ${\beta }$ ‐position of acetoacetate by homologation of acyl‐MIDA (N‐methyliminodiacetic acid) boronates with diazoacetates. Either alkyl or boryl groups were found to migrate with regiochemistry being a function of the steric bulk of the diazo species. Boryl β ${{\rm \beta }}$ ‐ketoesters can be further modified into borylated pyrazolones and oximes, thereby expanding the synthetic toolkit and offering opportunities for additional modifications. [ABSTRACT FROM AUTHOR]

In this communication, a straighforward asymmetric synthesis of spiro‐indoline‐pyrazolone compounds is described. This methodology consists in a formal [4+1] cycloaddition reaction of 4‐bromopyrazolones and aza‐ortho‐quinone methides generated in situ catalyzed by a bisquinine‐derived squaramide in CHCl3 under basic conditions. A variety of chiral spirocyclic compounds bearing a pyrazolone and an indoline moieties were obtained in moderate to good yields (up to 68 %) and moderate to excellent enantioselectivities (up to 93 % ee). [ABSTRACT FROM AUTHOR]

Pyrazolones derivatives are known for their pharmaceutical and therapeutic activities. In this regard, some new pyrazolone derivatives have been synthesized using cyclocondensation, nucleophilic substitution, and alkylation reactions. Their corresponding structures were elucidated using X-ray diffraction and NMR spectroscopic techniques. The experimental spectral data were compared with the predicted ones obtained at the B3LYP/6-311++G(d,p) level of theory. Geometrical parameters and chemical shifts are relatively well reproduced with correlation coefficients higher than 90%. The intercontacts in crystal units were investigated by the analysis of their corresponding Hirshfeld surfaces and fingerprint maps, which reveal that the major contacts are found for H...H intercontacts. Finally, the inhibition efficiency of the novel pyrazolone derivatives as SARS-CoV-2 Mpro is estimated by determining their binding affinities into the binding site of SARS-CoV-2 Mpro. The docking results reveal that the current pyrazolone derivatives may act as potent inhibitors of SARS-CoV-2 Mpro and that their inhibition efficiency may be strongly influenced by the substituted functional groups of pyrazolone moiety. Synthesis of new 4-Substituted Pyrazolone derivatives Good correlations are obtained between the spectra and X-ray data with the predicted ones. Hirshfeld surface analysis is used to analyze intermolecular interaction. 3D molecular structure is characterized using x-Ray and spectroscopic techniques. Interactions for of the newly synthesized compounds 2b, 3b, 3a, and 4 docked SARS-CoV-2 Mpro/PDB: 6LU7-A chain protein. [ABSTRACT FROM AUTHOR]

In the title compound, C12H11N3OS, the interplanar angle between the pyrazole and benzothiazole rings is 3.31 (7)°. In the three-dimensional molecular packing, the carbonyl oxygen acts as acceptor to four C--H donors (with one H…O as short as 2.25 Å), while one methyl hydrogen is part of the three-centre system H…(S, O). A double layer structure parallel to (...01) can be recognized as a subsection of the packing. [ABSTRACT FROM AUTHOR]

This paper presents an efficient one-pot approach for synthesizing hydroxylated 1,3-dithiane-pyrazolone hybrids. The process involves a reaction between pyrazolone derivatives, carbon disulfide, and epichlorohydrin (ECH). The structures of the produced 1,3-dithian-pyrazolone hybrids are determined based on their IR, 1H NMR, 13C NMR, and Mass spectroscopic data. Analysis of the 1H NMR spectra of compounds 4b and 4d revealed first-order splitting of the methylene hydrogens of the 1,3-dithian moiety, indicating that the OH group occupies an axial position in the preferred conformation of these derivatives. Despite the use of optically pure ECH as a starting material, racemization of products occurs during the reaction. The proposed reaction mechanism provides a rational explanation for this observation. [ABSTRACT FROM AUTHOR]

In this study, we successfully synthesized ethyl 2-(3-methoxybenzyl) acrylate-substituted pyrazolones derivative (EMH) through the reaction of Baylis-Hillman acetate with pyrazolones. We conducted comprehensive screenings to evaluate its invitro antifungal, antibacterial, and antioxidant properties. The molecule demonstrated notable in vitro antifungal and antibacterial activities attributed to the presence of anisole, enhancing absorption rates through increased lipid solubility and improving pharmacological effects. Structure-activity relationship (SAR) studies supported these findings. Additionally, insilico studies delved into the molecular interactions of the synthesized molecule with DNA Gyrase, Lanosterol 14 alpha demethylase, and KEAP1-NRF2 proteins, revealing strong binding interactions at specific sites. Furthermore, we employed ab-initio techniques to theoretically estimate the photophysical properties of the compounds. Ground state optimization, dipole moment, and HOMO-LUMO energy levels were calculated using the DFT-B3LYP-6-31G(d) basis set. The theoretical HOMO-LUMO values indicated high electronegativity and electrophilicity index. NBO analysis confirmed the presence of intermolecular ON...H hydrogen bonds resulting from the interaction of the lone pair of oxygen with the anti-bonding orbital. Overall, our results suggest that anisole-substituted pyrazolones derivatives exhibit promising applications in both photophysical and biological domains.

The first (5+1) annulation of allenoates and pyrazolones catalyzed by CH3OK has been reported. A series of spiro-pyrazolone derivatives were obtained as single diastereomers in high yields (≤95%) under mild conditions. The synthetic utility was demonstrated by a scale-up reaction and various transformations of the products. The proposed mechanism suggests that the allenoate works as a 1,5-biselectrophilic 5C synthon for the first time and controlled experiments disclose that K+ plays an important role in the diastereoselectivity-determining step through an eight-membered ring transition state. Also, this 1,5-biselectrophilic allenoate will be able to act as a 5C synthon for (5+n) annulation. [ABSTRACT FROM AUTHOR]

A diastereo‐ and enantioselective synthesis of spirocyclopropylpyrazolones has been described through a Michael/alkylation cascade reaction of 4‐arylidenepyrazol‐5‐ones with diethyl 2‐bromomalonate catalyzed by (DHQ)2AQN. The reaction afforded selectively the corresponding spirocyclic compounds with 30–83% yield, diastereoselectivities ranging from 60:40 to >95:5 and 26–93% enantiomeric excess under mild reaction conditions. Moreover, we performed two selective transformations with the corresponding chiral compounds. [ABSTRACT FROM AUTHOR]

Spirocyclic compounds have always attracted attention due to their presence as a structural core in a wide variety of natural and bioactive molecules and to exhibit pharmaceutical properties. An asymmetric synthesis of spiro[indoline‐3,4′‐pyrano[2,3‐c]pyrazoles] via Michael addition of trifluoromethyl substituted pyrazolone to isatylidene ethyl cyanoacetate derivatives was conducted with excellent enantioselectivities up to 99 % and up to 97 % isolated yield at room temperature with using 2 mol % of bifunctional quinine derived squaramide organocatalysts. [ABSTRACT FROM AUTHOR]

Here we present a [3+2] cycloaddition of rationally designed trisubstituted cyclic α‐chloroamides, primarily those incorporating pharmacological pyrazolone cores, as potent synthons for synthesizing valuable spirocyclic γ‐lactam architectures. This protocol exhibits 52–96% yields, impressive substrate compatibility, and scale‐up capacity. Importantly, this study also represents one of the rare examples that harness enaminone C−N bond cleavage to engineer relevant spirocyclic γ‐lactam skeletons of biological interest. Moreover, we propose a plausible mechanistic explanation to elucidate the outstanding chemical outcomes observed, thereby enriching the synthetic toolbox for pyrazolone chemistry and α‐haloamide‐mediated reactions. [ABSTRACT FROM AUTHOR]

Pursuing on our efforts towards searching for efficient anticancer agents herein we have designed and synthesized pyrazolone derivatives of 7‐amino 4‐methyl coumarin and 6‐amino coumarin. Anticancer activity of all the compounds were performed against lungs cancer cell line (A549) and breast cancer cell line (MCF‐7) using MTT assay. Out of all the compounds, compounds 17 c and 19 b exhibited remarkable activity with IC50 value of 1.22 μM and 1.66 μM against lungs cancer cell line (A549) breast cancer cell line (MCF‐7) respectively. Consequently, both compounds 17 c and compound 19 b were selected to study their cytotoxicity mechanism using different assays which includes EtBr/AO assay in respective cell, quantification of ROS using DCFH‐DA dye. To explore the behavioral and selective properties of the synthesized molecules, experimental analysis was complemented with computational methods. The electronic and structural parameters for both compound 17 c and 19 b were calculated using density functional theory (DFT) calculations and correlated with the observed biological activity. Molecular docking was conducted to explore the interaction of compounds 17 c and 19 b with pivotal apoptotic genes, namely p53 and caspase 3. Compound 17 c exhibited docking scores of −8.6 and −8.4 kcal/mol for p53 and caspase 3, while compound 19 b showed scores of −9.3 kcal/mol for both genes, significantly surpassing fluorouracil. Hence, compound 17 c and 19 b can be pursued for further studies, including molecular and In Vivo investigations. [ABSTRACT FROM AUTHOR]

An effective protocol for synthesis of some new pyrazolone-substituted C-acylimine derivatives is reported through a one-pot three-component reaction between arylglyoxals, aniline derivatives and pyrazolone. All reactions were conducted in ethanol/acetic acid mixture as solvent and the stable products were obtained by simple filtering off the precipitated solids in high yields. The structures of all products were proved by 1H and 13C NMR and IR spectral and elemental analysis data. [ABSTRACT FROM AUTHOR]

The essential aim of the present study is designed to utilize 4,9-dimethoxy-5-oxo-5H-furo[3,2-g]chromene-6-carbonitrile (1) to build some novel heterocyclic systems containing benzofurans as well as furo[3,2-g]chromenes. Ring opening ring closure reactions of compound 1 with N-phenyl-2-cyanoacetamide produced 8-amino-furochromenopyridine-7-carboxamide 2, which cyclized with some electrophilic reagents giving furochromenopyridopyrimidines (63–73% yields). The reaction of carbonitrile 1 with pyrazolone derivatives yielded furochromenopyrazolopyridines 10 and 11 in good yields. Also, benzo[h]furochromeno naphthyridine 13 was synthesized from recyclization of carbonitrile 1 with 1-ethyl-4-hydroxyquinolin-2(1H)-one (12). On a different mechanism, recyclization of carbonitrile 1 with some 1,3-binucleophiles afforded pyrido[2,3-d]pyrimidines (14 and 15), pyrimido[1,2-a]pyrimidine 17 and pyrimido[2,1-c][1,2,4]triazine 19 in suitable yields (62–71%). Finally, the reaction of carbonitrile 1 with 1,3-cyclohexanedione and 1,4-cyclohexanedione in 2:1 molar ratio yielded polyfused systems 20 and 21, respectively. Based on spectral and analytical results, the structures of the all products were inferred. [ABSTRACT FROM AUTHOR]

Efficient access to the tetracyclic pyrazolo-fused carbo- and N-heterocyclic systems: naphtho [2',1':3,4]cyclohepta[2,1-c]pyrazolones, naphtho[2',1':5,4]azepino[6,7-c]pyrazolones, naphtho [2',1':5,4]azocino[6,7-c]pyrazolones and naphtho[2',1':6,5]azonino[7,8-c]pyrazolones is described involving intramolecular Friedel--Crafts cycliacylations of synthesized pyrazole-based carboxylic acid or ester derivatives aided by treatment with Lewis and Brønsted acids. The required starting carbaldehyde was obtained by the Vilsmeier--Haack reaction of the corresponding 2-acetylnaphthalene hydrazone. Our developed strategy, involving a three-step route, offers easy access to tetracyclic pyrazole-fused systems in moderate to good yields. [ABSTRACT FROM AUTHOR]

A new azo dye was produced by mixing 1-(4-sulfophenyl)-3-methyl-5-pyrazolone with diazonium salt from luminol. The produced dye was assessed using the FT-IR, ¹HNMR, and UV-Visible spectroscopy techniques. This dye was dissolved in five polar solvents, and its UV-visible absorption spectra were measured and spectroscopically analysed at room temperature. Additionally, an atomic force microscope (AFM) was used to measure the enhancement of CO3O4 and ZrO2 nanoparticles in luminol azo 1-(4 -sulfophenyl)-3-methyl-5- pyrazolone solutions in aqueous solution. [ABSTRACT FROM AUTHOR]

This article discusses the construction of polyfluorinated aromatic compounds and their potential applications in various industries, including pharmaceuticals. The authors focus on the defluorinative O-arylation of pyrazolones with polyfluoroarenes, a metal-free catalyzed reaction that allows for the synthesis of valuable compounds under mild conditions. The authors provide experimental results and optimization studies to support their findings. They also highlight the limitations of their approach and mention ongoing research to address these limitations and expand the scope of their method. [Extracted from the article]

In the current study, dapsone and different 4-acyl pyrazolone derivatives have been used to synthesise various Cu(II) and Ni(II) based heterochelates. Elemental analysis, ¹H NMR, IR, and mass spectroscopy have been utilized to check the structure of the tetra dentate DPL1 to DPL5 ligands, and FAB mass spectroscopy as well as temperature investigations (TGA/DTG and DSC) have been utilized to approve the structure of the Cu(II) and Ni(II) heterochelates. All the synthesized compounds have been examined for their in vitro biological study against two Gram +ve (Bacillus cereus, Bacillus megaterium) and two Gram -ve (Escherichia coli, Enterobacter aerogene) microorganisms as well as their MIC against two Gram +ve (Bacillus subtilis, Staphylococcus aureus) and two Gram -ve (Escherichia coli, Serratia marcescens) microorganisms. The outcomes demonstrate the tremendous promise and importance of novel bis-pyrazolone heterochelates based on dapsone for further study. [ABSTRACT FROM AUTHOR]

An electrochemical/I– dual-catalyzed access to sulfonated pyrazoles from pyrazolones and sodium sulfites under external oxidant-free conditions has been developed. This established electrochemical reaction works smoothly under external oxidant-free conditions and has the advantages of good functional group tolerance, easy to gram-scale synthesis, delivering up to 95% yield for 35 examples.

A chiral sulfonamide-phosphine catalyzed regio- and enantioselective (3 + 3)-annulation of 2-(4H-benzo[d][1,3]oxazin-4-yl)acrylates with 2,4-dihydro-3H-pyrazol-3-ones has been established, affording a wide range of such 1,4,5,6-tetrahydropyrano [2,3-c]pyrazole-containing carboxylates in generally high yields (61–96%) with high diastereo- and enantioselectivities (8:1->20:1 dr, 85–95% ee). Based on several control experiments, a reaction mechanism was proposed. Importantly, the work represents the first example of using benzoxazinyl acrylates as three-atom synthons, which enriches the chemistry of benzoxazinyl acrylates.

Under the catalysis of Rh2(OAc)4 (10 mol%) and binapbisphosphine ligand (±)-L3 (20 mol%) in DCE at 80 °C, the cascade cyclization of diazoimides with alkylidenepyrazolones underwent stereoselectively (dr > 20:1), affording pyrazole-fused oxa-bridged oxazocines in reasonable chemical yields. The chemical structure and relative configuration of title products were firmly identified by X-ray diffraction analysis. [ABSTRACT FROM AUTHOR]

In order to search for efficient antioxidants of the pyrazolone series, sulfur-containing derivatives of 2,4-dihydro-3H-pyrazol-3-one and 1H-pyrazole (1a–e) were studied in the model system of radical chain oxidation of 1,4-dioxane. The antioxidant activity of these compounds was determined. The rate constant for the reaction of peroxyl radicals with inhibitor 1 (k7) and stoichiometric inhibition coefficient (f) were calculated at 333 K. Sulfur-containing 2,4-dihydro-3H-pyrazol-3-ones exhibit a higher antioxidant activity fk7 = (5.7–9.2)·104 L mol−1 s−1) than 4-(pentylsulfanylmethyl)-3,5-dimethyl-1H-pyrazole fk7 ⩽ 2 · 103 L mol−1 s−1), which is possibly due to the presence of the hydroxyl group in the pyrazolone cycle in the hydroxy form. The stoichiometric coefficients of inhibition for 4-(benzylsulfanylmethyl)-5-methyl-, 5-methyl-4-(pentylsulfanylmethyl)-, and 5-methyl-4-(propylsulfanylmethyl)-2,4-dihydro-3H-pyrazol-3-ones f = 0.95–1.3) indicate the "decay" of one peroxyl radical on one inhibitor molecule. In the case of 5-methyl-4-[(2-propylsulfanyl)methyl]-2,4-dihydro-3H-pyrazol-3-one, the stoichiometric coefficient of inhibition decreases f = 0.59). [ABSTRACT FROM AUTHOR]

Three different types of dioxidomolybdenum(VI) complexes of 4‐acetyl‐3‐methyl‐1‐phenyl‐5‐pyrazolone (Hmp, I)), 3‐methyl‐1‐phenyl‐4‐propionyl‐5‐pyrazolone (Hpp, II), 4‐butyryl‐3‐methyl‐1‐phenyl‐5‐pyrazolone (Hbutp, III), and 4‐isobutyryl‐3‐methyl‐1‐phenyl‐5‐pyrazolone (isobutp, IV) have been isolated and characterized by various spectroscopic (FT‐IR, UV/Vis, 1H and 13C NMR) techniques, thermal analysis and single crystal X‐ray analysis. These complexes adopt a distorted six‐coordinate octahedral geometry where ligands act as bidentate, coordinating through the two O atoms. These complexes have been used as catalysts to explore a single pot multicomponent (benzaldehyde or its derivatives, urea/thiourea and ethyl acetoacetate/phenyl acetoacatate) Biginelli reaction producing biologically active 3,4‐dihydropyrimidin‐2‐(1H)‐one and 3,4‐dihydropyrimidin‐2‐(1H)‐thione based biomolecules under solvent‐free conditions. Presence of H2O2 improves the yield of dihydropyrimidin‐2‐(1H)‐one but it acts as poison for the later molecule. Epoxidation of internal and terminal alkenes mainly resulted in the formation of the corresponding epoxide. The catalytic oxidative bromination of thymol, a reaction facilitated by vanadium dependent haloperoxidases, resulted in the formation of three product namely 2‐bromothymol, 4‐bromothymol and 2,4‐bromothymol. Other phenol derivatives have also been brominated effectively. [ABSTRACT FROM AUTHOR]

In this study, an efficient one-pot, solvent-free synthesis of pyrazolone-1,3-dithiolan and pyrazolone-1,3-dithiole hybrids from the reaction between in situ generated pyrazolones and propargyl bromide in the presence of carbon disulfide is reported. This reaction was carried out in the presence of triethylamine at room temperature, and new pyrazolone-1,3-dithiolan and pyrazolone-1,3-dithiole hybrids were formed in good to high yields. In the 1H NMR spectra of synthesized 1,3-dithiole hybrid molecules, the signal of olefinic hydrogen appeared at about 7.07–7.41 ppm in DMSO-d6. The values of these chemical shifts indicate that both linked pyrazole and dithiole rings in the dithiole-pyarzolone hybrid molecules have aromatic properties. [ABSTRACT FROM AUTHOR]

Owing to the emergence of antibiotic resistance, the polymyxin colistin has been recently revived to treat acute, multidrug-resistant Gram-negative bacterial infections. Positively charged colistin binds to negatively charged lipids and damages the outer membrane of Gram-negative bacteria. However, the MCR-1 protein, encoded by the mobile colistin resistance (mcr) gene, is involved in bacterial colistin resistance by catalysing phosphoethanolamine (PEA) transfer onto lipid A, neutralising its negative charge, and thereby reducing its interaction with colistin. Our preliminary results showed that treatment with a reference pyrazolone compound significantly reduced colistin minimal inhibitory concentrations in Escherichia coli expressing mcr-1 mediated colistin resistance (Hanpaibool et al. in ACS Omega, 2023). A docking-MD combination was used in an ensemble-based docking approach to identify further pyrazolone compounds as candidate MCR-1 inhibitors. Docking simulations revealed that 13/28 of the pyrazolone compounds tested are predicted to have lower binding free energies than the reference compound. Four of these were chosen for in vitro testing, with the results demonstrating that all the compounds tested could lower colistin MICs in an E. coli strain carrying the mcr-1 gene. Docking of pyrazolones into the MCR-1 active site reveals residues that are implicated in ligand–protein interactions, particularly E246, T285, H395, H466, and H478, which are located in the MCR-1 active site and which participate in interactions with MCR-1 in ≥ 8/10 of the lowest energy complexes. This study establishes pyrazolone-induced colistin susceptibility in E. coli carrying the mcr-1 gene, providing a method for the development of novel treatments against colistin-resistant bacteria. [ABSTRACT FROM AUTHOR]

The pyrazolone-based 4-(furan-2-yl)benzoic acids have been synthesized and studied as xanthine oxidase inhibitors. This enzyme is one of the therapeutic targets for the treatment of hyperuricemia and related diseases. The compounds studied have found to exhibit low micromolar IC50 values relative to the enzyme in vitro, depending on substituents in position 3 of the pyrazolone ring. However, the inhibitory effects observed are reduced in the presence of bovine serum albumin or Tween-80. Among the pyrazolone derivatives synthesized, 4-(5-((3-methyl-5-oxo-1-phenyl-1,5-dihydro-4H-pyrazol-4-ylidene)methyl)furan2-yl)benzoic acid has been found to be the most potent inhibitor of xanthine oxidase. Kinetic results have shown that this compound is a mixed-type inhibitor with higher affinity to the free enzyme than to the enzyme-substrate complex. The results of the molecular docking and molecular dynamics show that the carboxylic group of the inhibitor can form a salt bridge with Arg880 and a hydrogen bond with Thr1010. These interactions can be key factors in the enzyme-inhibitor complex stabilization [ABSTRACT FROM AUTHOR]

A preparative approach to thiazole-containing chromone derivatives has been developed by modifying the corresponding aldehydes with their further transformation into propenone derivatives, and finally introducing them into the Algar-FlynnOyamada reaction. Several methods for obtaining propenones have been analyzed, and the most effective and practically convenient one has been found. The thiazole-containing analogs of chromones obtained have a great potential as probes for a wide range of studies. [ABSTRACT FROM AUTHOR]