Journal of Heterocyclic Chemistry最新文献

Photochemical properties of terarylenes with quinoxalines bridge unit and allomaltol fragment was investigated. We have demonstrated that starting compounds with hydroxyl group in 3-hydroxy-4-pyranone substituent does not undergo any photoinduced transformations. Wherein, conversion to methoxy derivatives allows one to realize photochemical 6π-electrocyclization for considered quinoxalines. Based on data of x-ray analysis the observed difference in reactivity is connected with the presence of hydrogen bond in hydroxyl derivatives. As a result of carried out research photochemical approach to novel benzo[a]pyrano[3,2-c]phenazin-4-ones was implemented.

A new and efficient method for synthesizing 1,3-oxazepines has been developed. The synthetic strategy of this method is based initially on the Knoevenagel reaction to form 5-benzylidine Meldrum's acid, followed by a 7-endo-cyclization reaction with TosMIC (p-toluenesulfonylmethyl isocyanide) in the presence of base. In the optimization studies carried out on this tandem reaction, the highest yield was obtained when K₂CO₃ was used as the base.

In this research article, the chemical synthesis of new N-phenylpyrazolone-N-benzylthiazole hybrids (3–6) via late-stage thiazolation of the corresponding benzylthiosemicarbazone 2 was reported. The skeletal structural of the new molecules were validated by instrumental measurements (FT-IR, NMR, and EI-MS). In vitro cytotoxicity-based cellular MTT bioassay shows that compound 3 that bears an N-benzyl-4-thiazolone moiety is the most potent one toward the osteosarcoma cell line (Hos) with an IC₅₀ value of 5.8 ± 0.1 μM, while compound 4a that contains a 5-acetyl-N-benzylthiazole unit is the most robust one against the model lung carcinoma cell line (A549) with an IC₅₀ value of 9.23 ± 0.01 μM. Also, 3 is roughly equipotent to 4b in its cytotoxicity activity against A549. In vitro enzymatic ELISA bioassay of A549 cells indicates that IC₅₀ of 3 caused a decrease in the pRIPK3 kinase concentration (2.89 ± 0.005 pg/mL) as compared to DMSO-treated cells (2.93 ± 0.010 pg/mL), while the pRIPK3 level incresed with 4b impact. As a result, 3 may be an effective inhibitor of pRIPK3 and hence necroptosis, proposing a novel therapeutic strategy for necroptosis-related illnesses. In silico molecular docking shows that 3 interlocked and fitted well into the binding site of RIPK3 (PDB code: 7MX3) with a fitness value (−123.382 kcal/mol) lower than 4b and forms an important H-bond with Lys50 like the marketed RIPK3 inhibitor GSK'843, validating the experimental results. Consequently, 3 is the most promising molecule that could be a lead candidate for further studies.

Dihydropyrimidinones (DHMPs) are the most important pharmacophore in Medicinal Chemistry. The synthetic approach for deriving DHMPs involves the Biginelli reaction or a combination of it with other multi-component reactions (MCRs). The scaffold has received considerable attention due to its diverse therapeutic activity. This review delves into the exploration of the biological characteristics of DHMPs, which play a pivotal role in various therapeutic areas including “anti-inflammatory, anti-HIV, anticancer, antitubercular, antifungal, antibacterial, antihyperglycemic, antihypertensive, anticonvulsant, antimalarial, antioxidant,” reverse transcriptase (RT) inhibitor, antispasmodic, calcium channel blockers, antiproliferative, urease inhibitor, cyclooxygenase (COX-2), and β-glucuronidase inhibitor activities. The insights provided in this review have the potential to aid researchers in the formulation of novel drugs, facilitating creation of more resilient, efficient, and safer therapeutic agents with reduced toxicity and minimized adverse effects.

In this study, we designed and synthesized a number of novel pyrido[3,4-d]pyrimidine-thiazolidine-1,2,4-oxadiazole derivatives and investigated them in vitro for their inhibitory action toward epidermal growth factor receptor (EGFR) kinases and antiproliferative activity against two different cell lines, MCF-7 and A-549. When compared to the lead chemicals, 5-fluorouracil and erlotinib, some of the compounds demonstrated acceptable activity. Among them, the most promising compounds 4d and 4e displayed potent anticancer activity against both MCF-7 and A-549 cell lines (IC₅₀ values remaining: 1.97 ± 0.28 μM to 8.14 ± 0.52 μM, respectively); the comparative IC₅₀ values for 5-fluorouracil and erlotinib in these cell lines were 5.56 ± 0.34 μM, 12.66 ± 0.76 μM, and 3.64 ± 0.49 μM, 9.54 ± 0.75 μM, respectively; as well as excellent kinase inhibitory activities (EGFR: IC₅₀ = 0.34 ± 0.07 μM and 0.42 ± 0.06 μM) were more effective than the conventional drug Erlotinib (IC₅₀ = 0.42 ± 0.02 μM).

In this research, investigation of one-pot multicomponent reactions of (1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione (curcumin), primary amines, and activated acetylenic compounds in an aqueous medium at room temperature in the presence of catalytic amounts of silica-coated magnetic nanoparticles functionalized by iminodiacetic acid-copper (Fe₃O₄@SiO₂/IDA-Cu) was studied which was produced 1,4-dihydropyridine-2,3-dicarboxylate in high yields. The advantages of this procedure were easy separation of products and catalyst, high yields of products, reusability of synthesized catalyst, and good rate of reactions.

In an attempt to cultivate energy-stability balance, a series of nitrogen and oxygen-rich high energy density materials were synthesized based on N-substituted 4-hydroxy-3,5-dinitropyrazole and methylene-linked N-amino-1,2,4-bridges. The hydroxy substituent contributed to oxygen content, hydrogen bonding, and tunability via salt formation. On the other hand, the triazole bridge delivered high nitrogen content and thermal stability. All the synthesized compounds were characterized with multinuclear NMR, FTIR, HRMS, and elemental analysis, and their physicochemical and energetic properties were analyzed. Energetic materials 1–5 showed high detonation performance and adequate overall stabilities. Compound 1 exhibited higher density (1.84 g/cm³) and detonation performance (D_v = 8103 m/s, P = 26.9 GPa) in comparison to its reported amino derivative.

One of the most often utilized hydroperoxides in an array of oxidation strategies is tert-butyl hydroperoxide (^tBuOOH, TBHP). The key reasons for rising utility of TBHP are its low cost, environmental friendliness, high efficiency, and ability to replace hazardous or rare heavy metal oxidants. In this sexennial update, we concisely and critically discussed the applications of TBHP in heterocyclic ring formations starting from 2018 to date. Merits and demerits of its utility, scope of a synthetic organic transformation along with mechanistic logistics are the key features of this review.

The present research study involves synthesis of 1,5-benzothiazepines has been prepared, derived from chalcones and 2-aminothiophenol in a catalytic amount of piperidine using different solvent conditions under microwave irradiation procedure with the aim to test their antibacterial activity and effect of different solvents in the synthesis. It resulted in good yield of 1,5-benzothiazepines (3a-j) and proved to be an efficient and environmentally benign procedure. The synthesized compounds were characterized by conventional spectral data and screened for their in vitro antibacterial activity against four pathogenic bacteria using agar diffusion method. The traditional classical heating method takes more reaction time. So, in this study, we have tested microwave irradiation process and found that 2-ethoxy ethanol as an alternative solvent in reducing the reaction time (up to 4–6 min.) with high yield as compared with classical method. The synthesized compounds 3a, 3c, 3d, 3e, 3 h, 3i, 3j exhibit good to moderate antibacterial activity.

Visible-light-mediated formation of tetrahydrobenzofuranone by direct oxidative [3 + 2] cycloaddition via coupling between dimedone and chalcone using eosin-Y as a photoredox catalyst has been reported. The reaction takes place by a radical pathway as evidenced from our experiments and literature. The developed method involves the utilization of visible-light photoredox catalysis for the formation of C-C and C-O bond via abstraction of methylinic hydrogen of dimedone and β-carbon of chalcone as well as coupling between carbonyl group of dimedone and α-carbon of chalcone in tetrahydrobenzofuranone in one-pot procedure. The present protocol shows significant advantages such as the application of visible light as a clean source of energy, green solvent, mild reaction conditions, cost effectiveness, short reaction time, metal free synthesis, easy operation, high atom economy, and broad substrate scope with functional group tolerance. Moreover, outstanding yield of the product obtained up to 82%.