Search Results (164)

Heterocyclic compounds are a common subject in the field of medicinal chemistry due to their numerous pharmaceutical applications. Among these, nitrogen- and oxygen-containing five-membered heterocyclic rings, namely oxazole and isoxazole, are particularly significant, exhibiting a broad spectrum of biological activities. Molecular hybridization, the process that enables the fusion of bioactive scaffolds, is a powerful strategy for the development of novel compounds characterized by enhanced or multitarget activities. This review focuses on hybrids incorporating linked oxazole and/or isoxazole moieties (i.e., isoxazole–oxazole and isoxazole–isoxazole hybrids), drawing upon peer-reviewed research articles and international patents from 1995 to the end of 2024. The overview systematically presents the diverse biological activities reported for the isoxazole–(iso)oxazole hybrids, including anticancer, antibacterial, antitubercular, anti-inflammatory, and antidepressant effects, alongside their corresponding chemical structures. Our analysis of the literature highlights the structural versatility and therapeutic potential of this important class of heterocyclic hybrids. Full article

The procedure for the generation of azirinyl-substituted nitrile oxides by the reaction of 2-(diazoacetyl)-2H-azirines with tert-butyl nitrite while preserving the azirine ring has been developed. The [3+2] cycloaddition of azirinyl-substituted nitrile oxides to terminal acetylenes produced azirinyl(isoxazolyl)ketones with various substituents in position 3 of azirine and position 5 of isoxazole fragments in a 51–91% yield at room temperature in DCM. DFT calculations and experimental data are consistent with the assumption that the formation of azirinyl-substituted nitrile oxides is accelerated by the acid catalyst. Cycloadducts of nitrile oxides with aryl/hetarylacetylenes and DMAD can be obtained by catalysis with boron trifluoride etherate, which significantly expands the scope of application of the reaction. Expansion of the azirine ring of the prepared cycloadducts allows obtaining a wide range of structurally diverse functionalized isoxazole-containing heterocyclic hybrids. LED light induces isomerization of the azirinecarbonyl moiety of the azirinyl(isoxazolyl)ketones, resulting in the formation of a set of 3,5’-biisoxazoles in a 40–71% yield, while the catalytic reaction of the azirine moiety with 1,3-diketones opens the way to pyrrole- and isoxazole-containing hybrids. 2-(Isoxazole-3-ylcarbonyl)-3-arylazirines were also easily isomerized to 3-(oxazol-5-yl)isoxazoles in methanol in the presence of excess potassium carbonate at room temperature. Full article

FRCM (Fabric-Reinforced Cementitious Matrix) composites, while providing an effective alternative to FRP (Fiber-Reinforced Polymer) strengthening systems when epoxy resins cannot be used, typically fail to achieve their full strengthening potential. Research indicates that appropriate mesh anchorage systems can minimize some of the undesirable effects that limit FRCM composite performance. This study investigates the effectiveness of different anchorage systems for PBO (p-Phenylene Benzobis Oxazole) fibers in FRCM composites used for strengthening reinforced concrete slabs. A series of unidirectionally bent RC slabs were tested under four-point bending: an unstrengthened control element, slabs strengthened with PBO-FRCM without anchorage, with bar anchorage (GFRP bar in a groove), and with cord anchorage (PBO cord through the slab). The research focused on analyzing the load–deflection behavior and key strain mechanisms that influence structural performance. The findings indicate that a single layer of PBO-FRCM increases bending capacity, raises yield load, and delays initial cracking. Most significantly, the research reveals substantial differences in composite mesh utilization efficiency. This study confirms that mechanical anchorage, particularly bar anchorage, significantly enhances the effectiveness of PBO-FRCM strengthening systems by delaying composite detachment and allowing for greater utilization of the high-strength fiber material. These results contribute valuable insights for RC slabs using FRCM composite systems and the anchorage of their mesh. Full article

Background/Objectives: Leukemia is a common cancer that arises in both children and adults when bone marrow’s hematopoietic stem cells proliferate unrestrained because of anomalies in normal cell regulatory systems. The present study focused on biological evaluation of oxazole-based oxadiazole scaffolds to evaluate the anti-proliferative effect on leukemic cancer cell lines. Methods: All novel oxazole-based oxadiazole scaffolds were synthesized and structurally characterized via ¹³C NMR, ¹H NMR, and HREI-MS. In order to identify an efficient anti-leukemia agent, the biological profiles of each compound were evaluated in comparison to the reference drug, Etoposide (IC₅₀ = 10.50 and 15.20 μM). Results: Analog 6 substituted with p-CF₃ at phenyl ring was identified with excellent inhibition against the HL-60 and PLB-985 cancer cell lines, with IC₅₀ of 8.50 and 12.50 μM. Through hydrogen bond formation, the trifluoromethyl moiety of analog 6 interacts with target tyrosine kinase enzyme (PDB-ID:4CSV). The interactive character of active ligands with target enzyme was demonstrated by molecular docking. The rate of inhibition in contrast with the drug concentration was also tested to check the inhibition percentage and inhibitor type via enzyme kinetics. Furthermore, the enzyme–ligand complex was also investigated via MD simulation along with pharmacophore modeling. DFT calculations were used to estimate the lead compounds’ relative stability and reactivity. According to ADMET investigation, there is safe toxicological profile for these compounds. Conclusions: The current study suggests that the potent compounds have significant anti-proliferative potential, and with further in vivo validation, hold promise for future optimization as potential leukemia treatments. Full article

The magnesium impurities in lithium carbonate cannot be detected quickly in an aqueous environment. To solve this bottleneck problem, this study proposes a new method for the rapid detection of trace Mg²⁺ in lithium carbonate using a water-soluble fluorescent probe. A water-soluble fluorescent probe A was obtained by introducing hydroxyl groups on a fluorescent oxazole ring. After modification, the hydrogen bonding between the probe and water molecules increased by more than 62 times. Consequently, the energy loss of outward transfer of the fluorescent probe increased, resulting in weak fluorescence in saline systems. Mg²⁺ was captured by N on the oxazole ring and O on the phenolic hydroxyl group through a 1:1 coordination ratio within the probe structure. The hydrogen bonding attraction between the complex and water molecules increased 16 times. Additionally, the orbital energy gap was reduced from 2.817 to 0.383 eV. Meanwhile, the Mg²⁺ impeded the phototropic electron transfer effect process, resulting in enhanced fluorescence and completing this process within 3 to 10 s, with a detection limit of 6.06 μmol/L. This method can promote the real-time and rapid quality control of Mg²⁺ impurities in the refining and purification of lithium carbonate, as well as effectively reduce production costs. Full article

Oxazole, a versatile and significant heteroarene, serves as a bridge between synthetic organic chemistry and applications in the medicinal, pharmaceutical, and industrial fields. Polycyclic aromatic compounds with amino groups substituted at the 2-position of an oxazole, such as 2-aminonaphthoxazoles, are expected to be functional probes, but their synthetic methods are extremely limited. Herein, we describe electrochemical reactions of 3-amino-2-naphthol or 3-amino-2-anthracenol and isothiocyanates in DMSO, using a graphite electrode as an anode and a platinum electrode as a cathode in the presence of potassium iodide (KI), which afford N-arylnaphtho- and N-arylanthra[2,3-d]oxazol-2-amines via cyclodesulfurization. This reaction is the first example of synthesis of 2-aminoxazole-based polycyclic compounds using an electrochemical reaction. An examination of the spectroscopic properties of polycyclic oxazoles revealed that the λ_abs value of the tetracyclic oxazoles was redshifted relative to that of the tricyclic oxazoles. Moreover, synthesized naphthalene/anthracene-fused tricyclic and tetracyclic oxazoles exhibited extended π-conjugated skeletons and fluoresced in the 340–430 nm region in chloroform. Full article

This research focuses on the removal of emerging contaminants (CEC) present in synthetic aqueous matrices. Azole compounds were selected as CEC of interest due to their persistence and toxicity, particularly the triazole and oxazole groups. These compounds are also trace contaminants listed in the proposed revision of Directive 91/271/EEC on urban wastewater treatment and the 3rd European Union Observation List (Implementing Decision EU 2020/116), highlighting their regulatory importance. The draft Directive includes the implementation of quaternary treatments to achieve the highest possible removal rates of micropollutants. Among the technologies used on a large scale are some advanced oxidation processes (AOP), often combined with adsorption on activated carbon (AC). Laboratory-scale pilot plants have been designed and operated in this research, including UV photolysis and oxidation with H₂O₂ and adsorption with GAC. The results demonstrate that UV photolysis is able to remove all the selected CECs except fluconazole, reaching eliminations higher than 86% at high doses of 31.000 J/m². Treatment by H₂O₂ achieved removals of 4 to 55%, proving to be ineffective in the degradation of persistent compounds when acting as a single technology. Adsorption by AC is improved with longer contact times, reaching removals above 80% for benzotriazole and methyl benzotriazole at short contact times, followed by sulfamethoxazole and tebuconazole. Fluconazole had a mean adsorption capacity at low contact times, while metconazole and penconazole showed low adsorption capacities. Full article

Benzylic C–H oxidation to form carbonyl compounds, such as ketones, is a fundamental transformation in organic synthesis as it allows for the preparation of versatile intermediates. In this review, we highlight the synthesis of aromatic ketones via catalytic, electrochemical, and photochemical oxidation of alkylarenes using different catalysts and oxidants in the past 5 years. Additionally, we also discuss the synthesis of heterocyclic molecules using benzylic C–H oxidation as a key step. These methods can potentially be used in medicinal, synthetic, and inorganic chemistry. Full article

Oxazoles are important five-membered heterocycles that contain both nitrogen and oxygen atoms. Due to their wide range of biological activities, many oxazoles demonstrate potential for extensive application in various fields, including medicinal chemistry. Trifluoromethyl carbinol, an important pharmacophore, contains both trifluoromethyl and hydroxyl groups and is common in molecules with important biological activities. Constructing oxazoles that contain a trifluoromethyl carbinol unit is undoubtedly important and valuable for expanding the chemical space in drug discovery. In this study, a simple and efficient method was developed for the synthesis of oxazoles containing a CF₃-substituted alcohol unit via the tandem cycloisomerization/hydroxyalkylation of N-propargylamides with trifluoropyruvates through a rational Lewis acid catalytic mechanism. This Zn(OTf)₂-catalyzed synthetic protocol is operationally simple and provides a series of oxazoles in moderate to good yields. The protocol demonstrates broad substrate scope, high functional group tolerance, and high atom economy and can achieve gram-level reactions, indicating the strong possibility of its practical application. Full article

A highly efficient method has been developed for preparing 2-((3R,9bS)-5,5-dioxido-2,3-dihydro-9bH-benzo[4,5]isothiazolo[3,2-b]oxazol-3-yl)-1-phenylethan-1-one. This enantioenriched title compound was obtained via an organocatalytic asymmetric [3+2]-cycloaddition of benzo[d]isothiazole 1,1-dioxide with (E)-4-hydroxy-1-phenylbut-2-en-1-one, using a bifunctional squaramide-based chiral catalyst. The reaction yielded 99% of the product with high enantioselectivity and diastereoselectivity (89:11 er and >20:1 dr). The structure of the newly synthesized compound was confirmed by ¹H-, ¹³C-NMR, IR and mass spectral data. Full article

A host–guest-based fluorescent composite with a large Stokes shift was synthesized by intercalating 2,2′-(thiophene-2,5-diyl)bis(benzo[d]oxazol-6-amine) (BBTA) into the nanochannels of zeolite L (ZL) and sealing the pores with (3-aminopropyl)triethoxysilane (APTES). To confirm the orientation of the amino groups in BBTA, a single crystal of 2,5-bis(6-nitrobenzo[d]oxazol-2-yl)thiophene (BBTN) was grown and examined by X-ray crystallography. The evidence of successful intercalation of BBTA into the nanochannels of ZL was provided by fluorescence spectrometry, gas sorption and fluorescence microscopy. BBTA showed a Stokes shift of 6641 cm⁻¹ (157 nm) in ethanol and 4611 cm⁻¹ (93 nm) in toluene. The BBTA-ZL composite (BBTA-ZL-s) showed a Stokes shift of 5677 cm⁻¹ (123 nm) in toluene, and 5450 cm⁻¹ (124 nm) in ethanol. In addition, the degree of loading was determined and stability against leaching was confirmed. We report the synthesis of this novel composite dye material with potential applications where free dyes are not applicable and which retains a large Stokes shift, independent of its chemical environment. Full article

Background/Objectives: Brick dust molecules exhibit high melting points and ultralow solubility. Overcoming this solubility issue is challenging. Previously, we formulated a co-amorphous system for a neuropeptide Y5 receptor antagonist (NP) as a brick dust drug using sodium taurocholate (ST) to improve its dissolution profile. In this study, we have designed a ternary amorphous system involving polymer addition to further improve a co-amorphous system. Methods: The amorphous samples were prepared by the ball milling. The thermal and spectroscopic analyses were performed, and the isothermal crystallization and dissolution profiles were evaluated. Results: The ball milling of NPs, ST, and each of the three types of polymers successfully converted crystalline NPs to amorphous NPs. Thermal analysis confirmed the formation of a single amorphous phase. The infrared spectra revealed a specific interaction between an NP and ST in the co-amorphous system. Moreover, the intermolecular interactions of NP-ST were maintained in the ternary amorphous systems, suggesting the miscible dispersion of the co-amorphous system into the polymer via weak interactions as co-amorphous solid dispersions. The dissolution profile of co-amorphous NP-ST was 4.1- and 6.7-fold higher than that of crystalline NPs in pH 1.2 and 6.8 buffers, respectively. The drug concentration in the ternary amorphous system in pH 1.2 and 6.8 buffers became 1.1–1.2- and 1.4–2.7-fold higher than that seen in the co-amorphous system, respectively. Conclusions: Co-amorphous solid dispersion is a promising method for enhancing the solubility of brick dust molecules. Full article

A synthesis of benzo[d]oxazoles by an N-deprotonation–O-S_NAr cyclization sequence from anilide precursors is reported. Anilides derived from 2-fluorobenzaldehydes, activated toward S_NAr ring closure by C5 electron-withdrawing groups, were prepared and subjected to deprotonation–cyclization using 2 equiv. of K₂CO₃ in anhydrous DMF. Following deprotonation at nitrogen, the delocalized anion cyclized from the amide oxygen to give high yields of benzo[d]oxazoles. The temperature required for the cyclization of benzanilides correlated with the potency of the C5 activating group on the S_NAr acceptor ring with nitro (most potent) reacting at 90 °C (1 h), cyano reacting at 115 °C (1 h), methoxycarbonyl reacting at 120 °C (2 h), and trifluoromethyl (least potent) reacting at 130 °C (3 h). Acetanilides were more difficult to cyclize but generally required 4–6 h at these same temperatures for completion. Product purification was accomplished by recrystallization or chromatography. Full article

Inspired by the potent tyrosinase inhibitory activity of phenolic compounds with a 2-phenylbenzo[d]thiazole scaffold, we explored phenolic compounds 1–15 with 2-phenylbenzo[d]oxazole, which is isosterically related to 2-phenylbenzo[d]thiazole, as novel tyrosinase inhibitors. Among these, compounds 3, 8, and 13, featuring a resorcinol structure, exhibited significantly stronger mushroom tyrosinase inhibition than kojic acid, with compound 3 showing a nanomolar IC₅₀ value of 0.51 μM. These results suggest that resorcinol plays an important role in tyrosinase inhibition. Kinetic studies using Lineweaver–Burk plots demonstrated the inhibition mechanisms of compounds 3, 8, and 13, while docking simulation results indicated that the resorcinol structure contributed to tyrosinase binding through hydrophobic and hydrogen bonding interactions. Additionally, these compounds effectively inhibited tyrosinase activity and melanin production in B16F10 cells and inhibited B16F10 tyrosinase activity in situ in a concentration-dependent manner. As these compounds showed no cytotoxicity to epidermal cells, melanocytes, or keratinocytes, they are appropriate for skin applications. Compounds 8 and 13 demonstrated substantially higher depigmentation effects on zebrafish larvae than kojic acid, even at 800- and 400-times lower concentrations than kojic acid, respectively. These findings suggest that 2-phenylbenzo[d]oxazole is a promising candidate for tyrosinase inhibition. Full article