Journal of Heterocyclic Chemistry最新文献

Benzothiazole alkaloids are a class of rare heterocyclic alkaloids with unique structures and exhibit a wide range of biological activities. So, the aim of this work is to investigate structural diversity-guided N-S heterocyclic derivatives based on natural benzothiazole alkaloids as potential cytotoxic agents. Three series of novel benzothiazole derivatives, including 22 compounds, were designed and synthesized using pharmacophore hybridization, and their in vitro cytotoxic activities against Huh-7 and A875 were fully evaluated. The results indicated that some of these benzothiazole derivatives had significantly good cytotoxic activities against two tested cell lines compared with the positive control 5-fluorouracil, and other compounds 3f–3i displayed good selectivity between A875 and Huh-7 cell lines, which might be used as promising lead molecule for discovery of novel benzothiazole-type cytotoxic agents.

The new type of the four-component tandem Knoevenagel–Michael reaction was discovered: the transformation of arylaldehydes, N,N′-dimethylbarbituric acid, malononitrile, and morpholine in alcohols and other organic solvents without any other additives at ambient temperature resulted in the selective formation of a new substituted unsymmetrical ionic scaffold with two pharmacology-active heterocyclic rings. This new four-component reaction is a simple and efficient route to a previously unknown substituted ionic unsymmetrical scaffold containing N,N′-dimethylbarbituric acid and morpholine. These ionic scaffolds are promising for various biomedical applications, for example, as anticonvulsants and anti-inflammatory drugs, as well as anti-AIDS agents. In this research, we also accomplished the efficient cyclization of morpholin-4-ium 5-(2,2-dicya-no-1-arylethyl)-1,3-dimethyl-2,6-di-oxo-1,2,3,6-tetrahydro-pyrimidin-4-olates by the action of NBS–NaOAc system, with the formation of 5,7-dimethyl-4,6,8-trioxo-2-aryl-5,7-diazaspiro[2.5]octane-1,1-dicarbonitriles in 83%–98% yields. In the final stage of our research, direct one-pot multicomponent transformation of benzaldehydes, N,N′-dimethylbarbituric acid, and malononitrile into spirobarbituric cyclopropanes was accomplished in 75%–97% yields. The spiro-barbituric cyclopropanes are potentially active as remedies against various inflammatory, infectious, immunological, or malignant diseases.

The oxidation of 5,5′-(methylene)bis(6-hydroxy-1,3-dimethylpyrimidine-2,4(1H,3H)-dione) monopiperidinium salts with Mn(OAc)₃•2H₂O was carried out in boiling MeCN, producing 2,4,9,11-tetramethyl-2,4,9,11-tetraazadispiro[5.0.5⁷.1⁶]tridecane-1,3,5,8,10,12-hexaones in high yields. A similar reaction using 4,4′-(methylene)bis(1,2-diphenylpyrazolidine-3,5-dione)s gave 2,3,8,9-tetraphenyl-2,3,8,9-tetraazadispiro[4.0.4⁶.1⁵]undecane-1,4,7,10-tetraones in good yields. The structure determination and the reaction mechanism for the formation of the unique tetraazadispiro(cyclopropane)s are discussed.

Imidazole is one of the most important heterocyclic rings. This nucleus can be found in a plethora of substances in different knowledge areas such as medicinal, agrochemical, polymer, and dyestuff. N-alkylation reactions involving N − 1 atom is a remarkable tool to synthesize many imidazole derivatives which can be attached to a great variety of functional groups. In this work, we synthesized 10 new intermediates 4-chlorobutyl 1-aryl-1H-pyrazole-4-carboxylates 3(a–j) from 1-aryl-1H-pyrazole-4-carbonyl chlorides, obtained from 1-aryl-1H-pyrazole-4-carboxylic acids 4(a–j), and 4-chlorobutan-1-ol 1, generated by THF ring-opening promoted by hydrochloric acid. Compounds 3(a–j) promoted N-alkylation of 4(5)-nitro-1H-imidazole to afford the targets 4-(4-nitro-1H-imidazol-1-yl)butyl 1-aryl-1H-pyrazole-4-carboxylates 2(a–j) in 18%–85% yields.

Protected lysine esters (Boc-L-Lys(Boc)-OSu) an intermediate of high repute in the peptide synthesis and diverse chemical synthetic applications, was the subject of synthetic process development studies, unveiling process-related impurities. These impurities were synthesized, characterized, and identified by different analytical tools, with their retention times verified by HPLC co-injection with commercial products. Detailed discussions ensued on the potential formation pathways and synthetic strategies of these process-related impurities.

Controlled oxidation of methyl-ketones to aryl glyoxals using Selenium dioxide and iodine is one of the useful transformation. Regardless the availability of many oxidation reagents, Iodine/DMSO system is very efficient and flexible. This system efficiently allows in situ formation of α-halo ketones and subsequently transforming them directly to useful products. The Iodine/DMSO system allows the selective CI and CO bond formation, substantially useful for converting them to other bond forming reactions and heterocycles useful in the synthetic and medicinal chemistry. Iodine/DMSO system could be an important alternative strategy due to sustainability, metal-free conditions, allowing multiple/linear domino reactions. This review will focus on heterocyclic systems smartly developed/manipulated by Wu group from methyl-ketones. The scope and limitations of this method and selected examples of applications for the synthesis of interesting molecules are discussed herein.

A rapid and efficient protocol for synthesizing two series of benzofuran-based hybrid polyheterocycles is presented: benzofuran-isatin and benzofuran N-acylhydrazones, and evaluation of their antibacterial activity both in vitro and in silico against two strains of Pseudomonas aeruginosa, PAO1 and PA14 were determined. Six of the tested compounds were shown to be active against the hypervirulent strain PA14. Docking studies were conducted using RNA polymerase sigmaS protein for P. aeruginosa PAO1 and PqsE protein for P. aeruginosa PA14 to provide additional insights into these results. A pharmacophore model was computed to suggest potential structural derivatives on the target molecules, offering further insights for future research. Finally, 40 novel compounds, including intermediates, were synthesized in a three-step reaction.

Antimicrobial resistance is one of the biggest threats to public health across the globe. Bacteria, fungi, viruses, and protozoans have been exhibiting resistance against antimicrobial drugs making them ineffective. Hence, the development of new antibiotics with a different mode of action is highly desirable. In this study, 10 new chromone-incorporated fused thiazolo[2,3-b]quinazolinone derivatives, 8a-j, have been prepared via Biginelli reaction involving aromatic aldehydes, 1-tetralone, and thiourea followed by a reaction with 2-chloro-N-phenylacetamide, and Knoevenagel condensation with 3-formylchromone. All the structures of the compounds were characterized by NMR, FTIR, and mass spectrometry. The in vitro antibacterial activities of all the synthesized compounds against the four different microbial strains were evaluated. Among them, few compounds demonstrated prominent activity against Staphylococcus aureus, Streptococcus pyogenes, and Pseudomonas aeruginosa. No appreciable activity of any compound against Klebsiella pneumoniae was observed. Molecular docking studies were employed to reveal the interactions responsible for the potent compounds' activities against S. aureus, S. pyogenes, and P. aeruginosa. Both in vitro and in silico studies have been carried out by using standard agar well diffusion protocol and Auto Dock Vina in PyRx. The results indicated that compound 8c was the potential compound as it showed good affinity toward the receptors of all three organisms. Molecular dynamics simulation of the 8c-1JIJ complex for 100 ns further confirmed the potentiality of 8c. The pharmacokinetic properties of the compounds indicate that the studied molecules have exhibited a favorable profile.

A large series of previously unknown isoxazole containing difluoroboron β-diketonate has been designed and synthesized from the available starting compounds. The photophysical properties of obtained compounds were studied, and the effects of the substituents in aromatic and isoxazole cycles of the BF₂ complexes on the fluorescence were investigated. The effect of solvatochromism were demonstrated. Cytotoxic activity against MCF-7 (breast carcinoma), HCT-116 (colon carcinoma), A549 (pulmonary carcinoma) and WI38 (fibroblasts from lung tissue) cell lines was tested and moderate toxicity in the concentration range of 10–100 μM was found for several compounds.