Journal of Heterocyclic Chemistry最新文献

New, high-yield derivatives of oxepino[3,2-c]chromene were synthesized through a multicomponent reaction. This reaction involved 2-hydroxyacetophenone, dimethyl carbonate, activated acetylenic compounds, and alkyl bromide. The reaction took place at room temperature in an aqueous environment, resulting in the formation of these innovative compounds. Oxathiepines were synthesized using multicomponent reactions of 2-hydroxyacetophenone, dimethyl carbonate, isothiocyanate, and alkyl bromide in water at room temperature. This technology offers several benefits, including quick response times, high product yields, and easy product separation using straightforward techniques.

In an effort to discover a new insecticide, we designed and synthesized a series of novel meta-diamide compounds containing 1,2,4-triazole with cyproflanilide as a lead compound. All the compounds were characterized by ¹H NMR, ¹³C NMR, and HR-MS. Both Plutella xylostella and Mythimna separata were tested for their insecticidal activity at 200 mg/L (P. xylostella: 0%–100%; M. separata: 0%–100%), 20 mg/L (P. xylostella: 0%–97%; M. separata: 0%–100%), and 2 mg/L (P. xylostella: 0%–97%; M. separata: 0%–100%), while Aphis craccivora was tested for its insecticidal activity at 400 mg/L (A. craccivora: 0%–36%). Further studies are needed to investigate the insecticidal activity of A. craccivora. Preliminary bioactivity results showed that most of the compounds had good insecticidal activity at 200 mg/L against P. xylostella and M. separata. Especially, the compound 7p, N-(cyclopropylmethyl)-N-(5-((2,6-dibromo-4-(perfluoropropan-2-yl)phenyl) carbamoyl)-2-(1H-1,2,4-triazol-1-yl)phenyl)-6-(trifluoromethyl)nicotinamide (7p), showed good insecticidal activity at even lower doses of 2 mg/L (P. xylostella: 97%; M. separata: 100%), which was equivalent to that of the lead compound cyproflanilide (P. xylostella: 100%; M. separata: 100%), as well as significantly better than the two known compounds I_a (P. xylostella: 97%; M. separata: 0%) and I_b (P. xylostella: 60%; M. separata: 0%). Preliminary structure–activity relationship was also discussed based on insecticidal tests. The results indicate that meta-diamide compounds containing 1,2,4-triazole can be developed as novel insecticides.

The first total syntheses of corallocins B and C are described herein. The Suzuki–Miyaura coupling was key to completion. Because these two natural products have been reported to induce neurotrophin expression in human astrocytes, they are expected to serve as new drug leads for neurodegenerative diseases.

This study focused on the investigation of synthesizing new derivatives of cyclopentapyridines with high yields employing multicomponent reaction that involved vinilydene Meldrum's acid, ethyl 2-amino-4-dioxo-4-arylbutanoates, hydrazonoyl chlorides, and activated acetylenic compounds. The reaction was conducted in water at room temperature, resulting in the synthesis of new compounds. Also, the reaction of synthesized cyclopentapyridines with dimethyl acetylenedicarboxylate was performed in water at room temperature which produced other cyclopentapyridine derivatives by elimination of N₂. The advantages of this technology encompass rapid response times, high product yields, and facile product separation via uncomplicated procedures.

Metal complexes have a significant impact on the treatment of human cancer. However, the scarcity of these compounds, resulting from their limited synthesis, hinders the comprehensive investigation of their anticancer mechanisms. Organic palladium compounds, known for their distinctive stability and properties, are thus an essential area of research in the development of anti-tumor therapy. In our study, we synthesized two novel ferrocene cyclopalladated compounds (C2 and C4). Its configuration was thoroughly characterized by employing ¹H, ¹³C NMR, ESI-MS, and elemental analysis techniques. The molecular structures were determined by X-ray single-crystal diffraction. In an in vitro anticancer study, it was observed that both C2 and C4 exhibited excellent suppression of viability in various tumor cell lines. These compounds showed better potency than cisplatin and demonstrated lower toxicity in normal cells. Particularly, C4 displayed approximately 22 times greater potency than cisplatin in suppressing melanoma cells (B16F10). Our study suggests that ferrocene cyclopalladated compounds have the potential to be promising candidates for the development of innovative anticancer drugs.

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).