oxazolone

Photochemically induced intramolecular hydrogen atom transfer in oxazolones is reported. An acetal or thioacetal function at the side chain acts as a hydrogen donor while the photochemical exited oxazolone is the acceptor. A one-step process─the electron and the proton are simultaneously transferred─is productive, while electron transfer followed by proton transfer is inefficient. Radical combination then takes place, leading to the formation of a C-C or C-N bond. The regioselectivity of the reaction is explained by the diradical/zwitterion dichotomy of radical intermediates at the singlet state...

An efficient divergent approach to functionalized naphthalene derivatives, the naphthalenamides, via base-mediated and silver-catalyzed cyclization has been developed using enone-oxazolones as the precursors. This protocol utilized base in methanol with heating to construct the corresponding hydroxynaphthalenamides 2 by a C-C bond formation, oxazolone ring-opening, and aromatization in good yields. On the other hand, phosphorylated dihydronaphthylamides 3 were generated by using H -phosphonate as the phosphonating reagent in a silver-catalyzed cyclization involving the phospha-1,4-addition/intramolecular ring closure with concomitant C-P/C-C bond formation in good yields...

We synthesized seven ( Z )-benzylidene-2-( E )-styryloxazol-5(4 H )-ones derivatives of cinnamic acid and evaluated the ability of these compounds to inhibit human acetylcholinesterase (hAChE). The most potent compound was evaluated for cognitive improvement in short-term memory. The seven compounds reversibly inhibited the hAChE between 51 and 75% at 300 μM, showed an affinity ( K i ) from 2 to 198 μM, and an IC50 from 9 to 246 μM. Molecular docking studies revealed that all binding moieties are involved in the non-covalent interactions with hAChE for all compounds...

Solid-state photoreactions are generally controlled by the rigid and ordered nature of crystals. Herein, the solution and solid-state photoreactivities of carbonylbis(4,1-phenylene)dicarbonazidate ( 1 ) were investigated to elucidate the solid-state reaction mechanism. Irradiation of 1 in methanol yielded primarily the corresponding amine, whereas irradiation in the solid state gave a mixture of photoproducts. Laser flash photolysis in methanol showed the formation of the triplet ketone (TK ) of 1 (τ ∼ 99 ns), which decayed to triplet nitrene 3 1N (τ ∼ 464 ns), as assigned by comparison to its calculated spectrum...

The inflammatory response in ulcerative colitis (UC) could be relieved by the conventional immunomodulatory agents; 5-aminosalicylic acid, corticosteroids, or azathioprine. However, the low remission rates and the intolerance to these agents necessitate investigation of gene expression signature in UC that could influence the therapeutic efficacy of drugs, as well as the interference with persistence genes by novel therapeutic option. Three microarray datasets (GSE66407, GSE38713 and GSE14580) from the NCBI-GEO database were utilized...

Delivery by cesarean section (CS) is associated with an altered gut microbiota (GM) colonization and a higher risk of later chronic inflammatory diseases. Studies investigating the association between CS and atopic dermatitis (AD) are contradictive and often biased by confounding factors. The aim of this study was therefore to provide experimental evidence for the association between CS and AD in a mouse model and clarify the role of the GM changes associated with CS. It was hypothesized that CS-delivered mice, and human CS-GM transplanted mice develop severe dermatitis due to early dysbiosis...

The 3,4-dihydrocoumarin derivatives were obtained from 2-alkyl phenols and oxazolones via C-H oxidation and cyclization cascade in the presence of silver oxide (Ag2 O) and p -toluenesulfonic acid as a Brønsted acid catalyst. This approach provides a one-pot strategy to synthesize the multisubstituted 3,4-dihydrocoumarins with moderate to high yields (64-81%) and excellent diastereoselectivity (>20:1).

Phosphodiesterase (PDE) 4 inhibitors have been approved for the treatment of atopic dermatitis (AD). However, the cellular and molecular mechanisms underlying their therapeutic effect remain to be fully elucidated. Here we addressed this unsolved issue by analyzing the action of difamilast, a novel PDE4 inhibitor, on an oxazolone (OX)-induced skin allergic inflammation commonly used as a mouse model of AD. Topical application of difamilast ameliorated skin inflammation in association with reduced IL-4 expression even when the treatment commenced 4 days after the initiation of OX challenge, showing its therapeutic effect on AD...

BACKGROUND: Basophils are rare but important effector cells in many allergic disorders. Contrary to their early progenitors, the terminal developmental processes of basophils where basophils gain their unique functional properties are unknown. OBJECTIVE: We sought to identify a novel late-stage basophil precursor and a transcription factor regulating the terminal maturation of basophils. METHODS: Using flow cytometry, transcriptome analysis and functional assays, we investigated the identification and functionality of the basophil precursors as well as basophil development...

The eyes provide themselves with immune tolerance. Frequent skin inflammatory diseases in young blind people suggest, nonetheless, that the eyes instruct a systemic immune tolerance that benefits the whole body. We tested this premise by using delayed skin contact hypersensitivity (DSCH) as a tool to compare the inflammatory response developed by sighted (S) and birth-enucleated (BE) mice against oxazolone or dinitrofluorobenzene at the ages of 10, 30 and 60 days of life. Adult mice enucleated (AE) at 60 days of age were also assessed when they reached 120 days of life...

The role of death-associated protein kinase1 (DAPK1) in post-stroke functional recovery is controversial, as is its mechanism of action and any neural remodeling effect after ischemia. To assess the debatable role of DAPK1, we established the middle cerebral artery occlusion (MCAo) model in DAPK1 knockout mice and Sprague-Dawley (SD) rats. We identified that the genetic deletion of the DAPK1 as well as pharmacological inhibition of DAPK1 showed reduced brain infarct volume and neurological deficit. We report that DAPK1 inhibition (DI) reduces post-stroke neuronal death by inhibiting BAX/BCL2 and LC3/Beclin1 mediated apoptosis and autophagy, respectively...

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by pruritus, erythema, and skin barrier dysfunction. Gasdermin D (GSDMD) is the key executioner of an inflammatory cell death mechanism known as pyroptosis. However, the role of GSDMD in the pathogenesis of AD remains unclear. Through the analysis of publicly available Gene Expression Omnibus (GEO) datasets, we observed an upregulation of Gsdmd mRNA in the skin tissue of AD patients. Moreover, we delved into the impact of GSDMD deletion and inhibition on AD-like skin lesions using a mouse model induced by the topical application of oxazolone (Oxa)...

Bimetallic synergistic catalysis is one of the most effective and powerful strategies for the synthesis of oxazolones, an important species in organic synthesis. In this work, the mechanism of AuCl(PMe3 )/AgOTf-Pd(0) ([Au-Pd]) bimetallic catalyst-catalyzed oxazolone synthesis using N -alkynyl carbamates as precursors was studied in detail by DFT calculations and the catalytic performances of a series of bimetallic catalysts were evaluated. The results show that the reaction begins from the [Au]-catalyzed cycloisomerization of N -alkynyl carbamates...

The in chemico direct peptide reactivity assay (DPRA) is validated to assess protein reactivity of chemical compounds, relating to the molecular initiating event of skin sensitization induction. According to OECD TG 442C, the DPRA is technically applicable to test multi-constituent substances and mixtures of known composition, even though limited experimental data are publicly available. First, we assessed the DPRA's predictive capability for individual substances, but at concentrations other than the recommended 100 mM, i...

The fragmentation characteristics of b 7 ions produced from proline-containing heptapeptides have been studied in detail. The study has utilized the following C-terminally amidated model peptides: PA6 , APA5 , A2 PA4 , A3 PA3 , A4 PA2 , A5 PA, A6 P, PYAGFLV, PAGFLVY, PGFLVYA, PFLVYAG, PLVYAGF, PVYAGFL, YPAGFLV, YAPGFLV, YAGPFLV, YAGFPLV, YAGFLPV, YAGFLVP, PYAFLVG, PVLFYAG, A2 PXA3 , and A2 XPA3 (where X = C, D, F, G, L, V, and Y, respectively). The results have shown that b 7 ions undergo head-to-tail cyclization and form a macrocyclic structure...

The benzoxazolone nucleus is an ideal scaffold for drug design, owing to its discrete physicochemical profile, bioisosteric preference over pharmacokinetically weaker moieties, weakly acidic behavior, presence of both lipophilic and hydrophilic fragments on a single framework, and a wider choice of chemical modification on the benzene and oxazolone rings. These properties apparently influence the interactions of benzoxazolone-based derivatives with their respective biological targets. Hence, the benzoxazolone ring is implicated in the synthesis and development of pharmaceuticals with a diverse biological profile ranging from anticancer, analgesics, insecticides, anti-inflammatory, and neuroprotective agents...

This paper describes the synthesis of new heterocycles from oxazol-5(4 H )-one and 1,2,4-triazin-6(5 H )-one classes containing a phenyl-/4-bromophenylsulfonylphenyl moiety. The oxazol-5(4 H )-ones were obtained via condensation of 2-(4-(4-X-phenylsulfonyl)benzamido)acetic acids with benzaldehyde/4-fluorobenzaldehyde in acetic anhydride and in the presence of sodium acetate. The reaction of oxazolones with phenylhydrazine, in acetic acid and sodium acetate, yielded the corresponding 1,2,4-triazin-6(5 H )-ones...

Atopic dermatitis (AD) is the most common chronically relapsing inflammatory skin disease, predominantly common in children; it is characterized by an eczematous pattern generally referable to skin dryness and itchy papules that become excoriated and lichenified in the more advanced stages of the disease. Although the pathophysiology of AD is not completely understood, numerous studies have demonstrated the complex interaction between genetic, immunological, and environmental factors, which acts to disrupt skin barrier function...

Dermal regulatory T cells (Tregs) are essential for maintenance of skin homeostasis and control of skin inflammatory responses. In mice, Tregs in the skin are characterized by high expression of CD103, the αE integrin. Evidence indicates that CD103 promotes Treg retention within the skin, although the mechanism underlying this effect is unknown. The main ligand of CD103, E-cadherin, is predominantly expressed by cells in the epidermis. However, because Tregs are predominantly located within the dermis, the nature of the interactions between E-cadherin and CD103-expressing Tregs is unclear...

Mycobacterium tuberculosis's (Mtb) success as a pathogen is due in part to its sophisticated lipid metabolic programs, both catabolic and biosynthetic. Several of Mtb's lipids have specific roles in pathogenesis, but the identity and roles of many are unknown. Here, we demonstrated that the tyz gene cluster in Mtb, previously implicated in resistance to oxidative stress and survival in macrophages, encodes the biosynthesis of acyl-oxazolones. Heterologous expression of tyzA (Rv2336), tyzB (Rv2338c) and tyzC (Rv2337c) resulted in the biosynthesis of C12:0 -tyrazolone as the predominant compound, and the C12:0 -tyrazolone was identified in Mtb lipid extracts...