Journal of Heterocyclic Chemistry最新文献

Cancer chemotherapy is continuously challenged by serious complications like pronounced side effects and multidrug resistance (MDR). Natural products, such as curcumin, offer promising alternatives due to their diverse biological applications and low toxicity. However, curcumin's clinical utility is limited by poor bioavailability, rapid metabolism, and non-specific (PAINS) activity. Building on previous findings, this study explored the structural modification of curcumin-inspired benzothiazepane derivatives in an attempt to enhance their therapeutic potential through modifications of the two peripheral (hetero)aromatic rings and the benzothiazepane scaffold. In this way, eight new 2-(hetero)aryl-4-(4-(hetero)aryl-2-oxobut-3-en-1-ylidene)benzothiazepanes and two 4-thiobutan-2-one “double Michael addition” derivatives were synthesized and tested for cytotoxicity against a panel of eight cancer cell lines. The screening results indicated that bis-(4-hydroxyphenyl) analogs bearing a chlorinated benzothiazepane ring exhibited the highest potency and broad-spectrum activity at the low micromolar range. Bis-substitutions with 3-pyridinyl and 2-furyl groups showed less potent but more specific activity profiles, potentially reducing PAINS effects. 2-Aminothiophenol-derived double Michael addition products demonstrated increased broad-spectrum activity, highlighting the importance of the free aniline amino group for targeted effects. This study underscores the potential of benzothiazepane derivatives as viable cancer cell cytotoxic agents and provides useful insights for future optimization and evaluation.

A novel series of N-carbamimidoyl-2,2,2-trifluoro-N′-arylacetimidamides (3a–j) have been prepared via condensation of 2,2,2-trifuoroacetimidoyl chlorides with guanidine in the presence Na and in dry EtOH solvent at ambient temperature. Then, these key intermediates were applied for the synthesized of 3-amino-4-aryl-5-(trifluoromethyl)-1H-1,2,4-triazoles (4a–j) under oxidative cyclization reaction in the presence of KI/I₂ as an oxidant system and DMSO solvent. The target compounds were produced in high yields and without the need for isolation.

Envisaging 5-aryltetrahydrobenzazepinone and 5-aryltetrahydrobenzazepines as conformationally locked potential B⁰AT1 inhibitors, a convenient synthetic route has been developed for their access. The synthetic route banks on using the Schmidt reaction for quick access to symmetrical/unsymmetrical 5-aryltetrahydrobenzazepinone and 5-aryltetrahydrobenzazepines.

The synthesis of 1,3-oxazines from 2-naphthol, benzaldehyde, and urea is reported using a simple and efficient microwave-assisted protocol. SiO₂-ZnCl₂ is employed for the first time to synthesize a library of 10 oxazin-3-one compounds, out of which five derivatives are novel. In 30–60 s the products were obtained with simplified work-up, the yield and purity were enhanced, and the reaction time was reduced with the use of microwave assistance. The synthesized oxazines were characterized and evaluated for their in vitro antioxidant properties. The results demonstrated a significant and effective presence of antioxidant capabilities. The compound 1-(4-hydroxy-3-methoxyphenyl)-1,2-dihydro-3H-naphtho[1,2-e][1,3]oxazin-3-one, containing hydroxy and methoxy groups, revealed superior antioxidant activity.

To explore the room-temperature synthesis of metal phthalocyanines with unsaturated substituents, two zinc phthalocyanines with unsaturated alkoxy groups were synthesized in a reaction system composed of 4-citronellol-oxy-phthalonitrile or 4-geraniol-oxy-phthalonitrile, Zn(OAc)₂⋅2H₂O, DBU, and ethanol, at room temperature. The synthetic reactions lasted for 7 days and the yields of two phthalocyanine derivatives reached 21% and 18%, respectively, and they are inclined to protonation in a non-coordinated organic solvent, for example, CHCl₃. By the way, the phthalocyanine compounds with other metals, such as Cu, Ni, and Co, cannot be prepared. This work will provide preference for improving the synthetic method in the future, so as to synthesize many new phthalocyanine compounds in general laboratories.

A rapid and direct route with the help of ultrasound for the synthesis of benzo[1,4,2]dioxazine derivatives through a copper iodide-catalyzed intermolecular O-arylation of N-hydroxyimidoyl chloride and 2-iodophenol in acetonitrile solvent has been investigated. The use of cheap and available raw materials and catalysts, without column chromatography, applying the sonochemical methodology, and performing the reaction in 40–45 min, with good efficiency (71%–93%) are notable features of this protocol. This research represents a significant advancement in the synthesis of benzo[1,4,2]dioxazine derivatives.

Nowadays, environmentally sustainable organic synthesis is demanding. In this context, nanoparticles are particularly interesting owing to their green synthesis aspects. Specifically, magnetic nanoparticles have been continuously utilized in organic synthesis for a decade. Among heterocycles, pyrrole and its analogs have a unique place due to its vast spectrum of applications. Derivatives of pyrrole help to find lead structures for new synthetic pharmaceutical compounds and other valuable compounds. Thus, magnetic nanoparticles accelerate organic chemists to develop pyrrole derivatives through green synthesis. Moreover, magnetic nanoparticles in pyrrole scaffold synthesis improve reaction efficiency and sustainability and create unique functional molecular hybrids for many scientific applications. This paper reviews the utilization of magnetic nanoparticles to afford a variety of valuable pyrrole derivatives, with a focus on their environmental friendliness.

The present protocol shows a novel and greener approach for synthesizing pyrazole amine thioether, employing thiophenol, 3-aminocrotononitrile, and phenylhydrazine hydrochloride. Notably, this methodology deviates from the literature report in making thioether derivatives using oxidant-free and room-temperature conditions. Based on the control experiments, it was found that the thioether link in the intermediate facilitated the 5-exo-dig cyclization reaction exclusively in the DMSO solvent. This is probably due to the nitrile group's activation by the structure's thioether moiety. The control experiment demonstrates the significance of the thioether compound in the reaction. Without any oxidizing agent, introducing thioether in any heterocyclic compound is not possible, as per the literature reports. Our reaction showed excellent tolerance by involving various phenylhydrazine hydrochloride and thiophenol compounds, allowing for the synthesis of various pyrazole amine thioether derivatives in good to excellent yields. The reaction follows the 5-exo-dig cyclization strategy.

CuI–Zn(OAc)₂ catalyzed a new, fast, solvent-free strategy for the synthesis of quinazolin-4(3H)-ones via selective scission of CC bond of the 1,3-diketone (both cyclic and acyclic) and β-ketoester was achieved under microwave irradiation. In contrast to the frequently applied synthetic strategy that involves cyclization-oxidation sequence of anthranilamides (2-aminobenzamides) with various aldehydes or benzyl alcohols, here, anthranilamide reacts with β-ketoester/1,3-diketo compounds in presence of CuI-Zn(OAc)₂ catalyst to form quinazolin-4(3H)-ones scaffold through an uncommon CC bond cleavage under solvent-free mild conditions with excellent yields. Besides, this method displays its capacity for gram-scale reactions.

A straightforward and an efficient green synthetic method has been outlined for the construction of 3-(benzo[d][1, 3] dioxol-5-yl)-1,8-naphthyridine derivatives in the presence of glacial acetic acid and Cu(OAc)₂ catalyst accomplished excellent yields in short reaction time. The reaction proceeds efficiently by using a greener way under microwave conditions to elevate the quantity of pure products. The purity of all the synthesized compounds was confirmed by IR, ¹H and ¹³CNMR, LC–MS data and also from the elemental analyses studies. The synthesized compounds 7d and 7f performed strongest antibacterial activity against pathogenic cell lines Bacillus subtilis (17.5, 20.5 mm), Escherichia coli (28.5, 30 mm), and antifungal cell lines Candida albicans (18, 22.5 mm), and Aspergillus Niger (28.5, 40.5 mm) which are compared with clinical drugs Penicillin, Grieseofulvin. We scrutinized the remaining molecules and found that their activity ranged from modest to exceptional.