Journal of Heterocyclic Chemistry最新文献

Succinate dehydrogenase inhibitor (SDHI) is an important fungicide to control grain diseases. For this reason, a series of novel pyrazole-4-carboxamide derivatives with an N-methoxy group were designed and synthesized. All the target compounds were characterized by ¹H NMR, ¹³C NMR, and HRMS. The compound 3c was further confirmed by X-ray diffraction, which crystallized in the triclinic system, space group P-1, Z = 2. The fungicidal activity results indicated that most of these compounds possessed good activity against Sclerotinia sclerotiorum at 50 ppm. Especially, compound 3h exhibited the best activity with the EC₅₀ is 7.80 μg/mL, which is comparable with the positive control bixafen (EC₅₀ = 6.70 μg/mL). Furthermore, the physicochemical properties, molecular docking simulation, ADMET analyses, DFT of compounds 3h, 3k and two commercial SDHIs, isoflucypram and pydiflumetofen, were investigated in this study.

A novel series of pyrimidine sulfonamide derivatives was synthesized through a strategic approach involving the creation of substituted dihydropyrimidinyl-benzenesulfonamides and subsequent transformation into their chlorinated analogues. These compounds were then subjected to reactions with various amines and phenols, yielding unique substituted sulfapyrimidines. These novel structures integrated essential pharmacophores such as phenols, secondary amines, and benzenesulfonamide moieties, each contributing distinct biological potencies, chemical reactivity, and enhanced pharmacological features. In the pursuit of effective anticancer agents, the newly substituted pyrimidine sulfonamides were characterized using spectroscopic and x-ray diffraction techniques. The compounds were evaluated for their anti-proliferative potency against the NCI 60-cell lines panel, revealing that compound 7c exhibited significant growth inhibition across multiple cancer cell lines. Further assessment through MTT assay on HCT-116 and MCF-7 cell lines demonstrated cytotoxicity, while cell cycle analysis of MCF-7 cells treated with compound 7c revealed arrest at the S phase. Moreover, the effect of 7c on programmed cell death was evaluated using the Annexin V/PI apoptosis assay. The observed promising activity positions these pyrimidine-based scaffolds as potential candidates for future drug development, offering valuable insights for medicinal chemists engaged in the design and synthesis of anticancer drugs.

Five new benzannulated steroid spiroketals were synthesized by Pd-catalyzed spiroketalization of 5α and 5β-alkynediols derived from stigmasterol and sitosterol. The detailed nuclear magnetic resonance (NMR) and X-ray characterization of the newly obtained spiroketals are presented. While the obtained compounds showed null or very low cytotoxicity, two of them inhibited more than 60% of the nitrous oxide production in J774A.1 macrophages stimulated with LPS, showing promising properties as anti-inflammatory agents.

Pyrazole derivatives are strategic structural motifs due to their proven utility in preparing chemicals in biological, pharmaceutical, photophysical, technological, and industrial fields; therefore, syntheses of pyrazole-containing compounds are highly desirable. Some nitrogen-rich pyrazoles, specifically nitrated derivatives posing high density and moderate thermal stability, have been used as energetic compounds since a high amount of energy is stored in their structures that can be released quickly with high detonation power under external stimuli (i.e., thermal, impact, and friction). These compounds have good capacity and sensitivity in explosives, propellants, and pyrotechnics applications in eco-friendly ways. Therefore, this contribution focuses on recent and illustrative examples regarding the (i) synthesis and reactivity of pyrazoles, especially works of the last decade, highlighting works on (ii) applications in energetic compounds to analyze their scope.

A total of 48 tetrahydrooxazolo-[5′,4′:4,5]pyrimido[1,2-a]azepinones were designed and synthesized from a scaffold hopping approach. All compounds were confirmed by analysis using ¹H NMR, ¹³C NMR, and HRMS techniques. The synthesized compounds were evaluated against the human cancer cell lines (HeLa, MCF-7, A549) in vitro, and the structure–activity relationships were summarized. The compound E43 exhibited the best inhibitory activity against HeLa, MCF-7, A549, displaying IC₅₀ values of 1.48 ± 0.13, 3.01 ± 0.09, and 5.11 ± 0.13 μM. Molecular docking indicated that compound E43 may bind to protein (PDB:6FEX) via hydrogen bond and π stacking. Further, molecular dynamics simulations indicated a relatively low binding free energy (−40.06 kJ·mol⁻¹) of compound E43 with protein. In conclusion, these findings suggested that E43 is promising as a potential novel anticancer drug candidate worthy of further investigation.

For the first time, the interaction of perfluoro-1,4-naphthoquinone with various 5-aminopyrazoles was investigated. It was shown that three types of products can be obtained depending on the structure of starting aminopyrazole. For all examples, the substitution of one fluorine atom in quinone moiety was observed. Wherein, in most cases, the starting aminopyrazoles act as a C-nucleophile leading to 2-(5-aminopyrazol-4-yl)-3,5,6,7,8-pentafluoronaphthalene-1,4-diones. At the same time substrates unsubstituted at ring nitrogen atom regiospecifically react at aminogroup resulting in the formation of 2,5,6,7,8-pentafluoro-3-((pyrazol-5-yl)amino)naphthalene-1,4-diones. Besides that, the absence of steric hindrance in the pyrazole unit allowed us to direct the process at nitrogen atom in Position 2 and synthesize zwitter-ionic 3-(5-aminopyrazol-2-ium-2-yl)-5,6,7,8-tetrafluoro-1,4-dioxo-1,4-dihydronaphthalen-2-olates. The structures of two types of obtained products were confirmed by x-ray analysis.

A GaCl₃-catalyzed [3 + 2]-cycloaddition/intramolecular esterification cascade of donor–acceptor cyclopropane-1,1-diesters with salicylaldehydes has been reported. A wide range of tetrahydro-4H-furo[3,2-c]chromen-4-ones have been efficiently delivered in moderate to good yields. Mechanistic studies suggest that the reaction involves the [3 + 2]-cycloaddition followed by intramolecular esterification to access 4H-furo[3,2-c]chromenones.

An efficient access to novel families of 7-membered dibenzodiazepines and 6-membered benzo[c]cinnoline derivatives has been elaborated. The synthetic strategy is based on a copper-catalyzed double N-arylation of cyclic diaryliodoniums with imidamides and 4-substituted 1, 2, 4-triazoline-3, 5-diones (TADs) respectively under ambient reaction conditions. A mechanistic rationale for the double N-arylation is discussed.

The synthesis of functionalized (trichloromethyl)quinazoline-4(1H)-one with high yields through a novel three-component intramolecular CH activation reaction from trichloroacetonitrile, benzoyl chlorides, and various primary amines is a remarkable achievement in organic chemistry. This strategy offers a direct and efficient route to access complex molecular structures from readily available starting materials. The use of copper (I) as a catalyst and L-proline as a ligand in tetrahydrofuran at room temperature highlights the importance of transition metal catalysis in enabling selective CH activation processes. Furthermore, the subsequent transformation of the obtained product with phenylacetylene and sodium azide in the presence of a copper catalyst in water solvent at room temperature demonstrates the versatility of this synthetic approach in accessing new (1,2,3-triazole)-quinazoline-4(1H)-one derivative. The combination of available starting materials, catalytic systems, mild reaction conditions, and ease of purification procedures contributes to the attractiveness of this method for the synthesis of diverse (trichloromethyl)quinazoline-4(1H)-one and (1,2,3-triazole)-quinazoline-4(1H)-one derivative.

Herein, we have developed palladium-trifluoroacetate-catalyzed carbo-palladation reaction of pyrrole-2-carbonitriles and aryl boronic acids leading to functionally diverse pyrrolo[1,2-α]pyrazines under thoroughly optimized reaction conditions. The reaction proceeded smoothly and allowed the diversity-oriented synthesis of pyrrolo[1,2-α]pyrazines with broad substrate scope with respect to pyrrole-2-carbonitriles and aryl boronic acids.