Journal of Heterocyclic Chemistry最新文献

The combination of visible light, a renewable and green energy source, and rose bengal, a non-toxic organic dye as a photoredox catalyst, is an easy and efficient method for synthesizing 3,4-dihydropyrimidin-2(1H)-ones/thiones in EtOH at ambient temperature in very short reaction time. The present work offers simple operation, easy workup, rapid conversion, and excellent product yields, while accommodating a wide range of substrates. Rose bengal-based photocatalytic approach permits foremost sustainability, which delivers economic and environmental rewards.

9-Aminoacridine structures hold much potential for accessing small molecule therapeutics. This core is present in a range of pharmaceuticals for the treatment of ailments such as malaria, inflammation, viral and bacterial infections, and cancer. For the latter, there remains a need to develop and/or improve chemotherapeutics to counteract issues of uptake, drug resistance, and selectivity for cancer cells over healthy cells. In the design of molecules to address these issues, identifying structural units that present as promising leads for drug development is key. In this study, four 9-aminoacridine derivatives under consideration as precursors for a drug design project are assessed for their cytotoxicity with representative cell lines PC3 and A549 and for their leadlikeness with SwissADME. Together, the cytotoxicity and in silico investigations coalesce around the same derivative as the most promising lead.

The histone deacetylases (HDACs) are being explored as a promising therapeutic target for the treatment of various diseases. Here, the synthesis of a series of pyrimidine-based 1,3,4-oxadiazoles, in which the oxadiazole scaffold is attached to the pyrimidine ring via a methyleneoxy spacer, is described and their HDAC inhibitory activity studied. The target compounds were synthesized by sequence of reactions involving O-alkylation of 2-(methylthio)pyrimidin-4(3H)-ones with ethyl 2-bromoethanoate followed by oxidation of the 2-methylthio group, displacement of the obtained 2-methylsulfonyl group with amines, hydrazinolysis of the obtained ethyl (2-amino-substituted pyrimidin-4-yloxy)acetates to give the corresponding hydrazides and their cyclization under the treatment with ethyl O-ethyl xanthate or carbonyldiimidazole to 1,3,4-oxadiazole-2(3H)-thiones and 1,3,4-oxadiazol-2(3H)-one, correspondingly. In addition, two 1,3,4-oxadiazole-2(3H)-thiones were converted into (N3)-morpholinomethyl derivatives by the Mannich reaction with formaldehyde and morpholine. The yields of intermediates and target compounds ranged from moderate to excellent. The synthesized compounds were characterized by ¹H and ¹³C NMR spectra and HRMS data, their purity was controlled by TLC. The synthesized pyrimidine-based 1,3,4-oxadiazoles (18 compounds) were tested as inhibitors of the HDAC4 and HDAC8 isoforms and their inhibitory activity was compared with that of Vorinostat. Most of the oxadiazolethiones containing methyl group at the position 6 of the pyrimidine moiety were found to be more selective towards HDAC8, while oxadiazolethiones with propyl group in the pyrimidine ring were active against HDAC4. Among the tested compounds, 5-((2-(dibutylamino)-6-propylpyrimidin-4-yloxy)methyl)-1,3,4-oxadiazole-2(3H)-thione (48) was found to have the strongest inhibitory activity for HDAC4 isoform (IC₅₀ = 4.2 μM vs. IC₅₀ = 59 μM for Vorinostat) while 5-((2-(cyclopentylamino)-6-propylpyrimidin-4-yloxy)methyl)-1,3,4-oxadiazole-2(3H)-thione (50) was the most potent HDAC8 inhibitor (IC₅₀ = 6.8 μM).

Heterocyclic compounds based on 1,3,4-oxadiazole (ODA) have attracted considerable attention in the field of pharmacy, drug discovery, and in the field of material sciences. This article reports a series of new highly twisted blue- and green-emitting ODA-based materials 4(a–e) utilizing a simple and efficient synthetic approach, resulting in high yield. The formation of multiple CN bonds unfolds via a simple nucleophilic method that does not need costly metal catalysts. The derivative structures were validated using analytical methods such as ¹H NMR, ¹³C NMR, and high-resolution mass spectrometry (HRMS). Using fluorescence spectroscopy, UV–Vis spectroscopy, and fluorescence lifetime measurements, a thorough investigation was carried out on the photophysical characteristics of the newly synthesized derivatives. A deeper understanding of intramolecular charge transfer was uncovered via solvent-dependent spectroscopy. Specifically, these materials show a large stock shift of up to 153 nm and long fluorescence decay value between 8 and 8.6 ns. Computational methods pinned on density functional theory (DFT) were used to determine the highest occupied molecular orbital–lowest unoccupied molecular orbital energy gaps. The optical band gaps derived from absorption peaks and the band gaps computed by DFT computations are highly correlated. Using cyclic voltammetry study, the compounds' redox potentials were further investigated. These results indicate that the ODAs 4(a–e) are promising organic materials and could play an important role in the field of optoelectronic devices, bioimaging, and photo-redox reactions.

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.