Chemistry of Heterocyclic Compounds最新文献

The reaction of 4-amino-substituted 6-hydrazinyl-1,3,5-triazin-2(1H)-ones with triethyl orthoacetate proceeded as a cascade reaction. The initially formed 7-amino-substituted 3-methyl[1,2,4]triazolo[4,3-a][1,3,5]triazin-5(1H)-ones underwent a Dimroth-type rearrangement with the formation of 5-amino-substituted 2-methyl[1,2,4]triazolo[1,5-a][1,3,5]triazin-7(3H)-ones. The latter underwent alkylation at three positions: at the exocyclic oxygen atom with the formation of 7-ethoxy-2-methyl[1,2,4]triazolo[1,5-a][1,3,5]triazines, at the N-3 nitrogen atom with the formation of 3-ethyl-2-methyl[1,2,4]triazolo[1,5-a][1,3,5]triazin-7(3H)-ones, and at the N-1 nitrogen atom to form 1-ethyl-2-methyl[1,2,4]triazolo[1,5-a][1,3,5]triazin-7(3H)-ones. For the latter compound, a retro-Dimroth-type rearrangement occurred with the formation of betaine-type 7-amino-substituted 2-ethyl-3-methyl[1,2,4]triazolo[4,3-a][1,3,5]triazin- 2-ium-5-olates. A possible mechanism for the alkylation of 5-amino-substituted 2-methyl[1,2,4]triazolo[1,5-a][1,3,5]triazin-7(3H)-ones with ortho esters was proposed.

The condensation of 3-[(alkylsulfanyl)methyl]pentane-2,4-diones with aniline in the presence of catalytic amounts of acetic acid led to the formation of 1,1',1''-(6-methyl-1-phenyl-1,2,3,4-tetrahydropyridine-3,3,5-triyl)triethanone. The reaction is presumably a tandem process, incorporating the formation of β-enaminone, elimination of the alkanethiol molecule from the β-enaminone and the starting pentane-2,4-dione, and a subsequent [4+2] cycloaddition of the resulting intermediates. The mechanism of the conversion may also involve intramolecular cyclization of the Michael addition products of 3-[(alkylsulfanyl)methyl]pentane-2,4-dione to 3-(imidoyl)but-3-en-2-one, formed from β-enaminones during the elimination of alkanethiols.

A set of 1-(2-amino-4H-thiazolo[5,4-b]indol-4-yl)ethan-1-one derivatives and their formally "hydrated" counterparts 1-(2-amino-8bhydroxy-3a,8b-dihydro-4H-thiazolo[5,4-b]indol-4-yl)ethan-1-ones were synthesized and characterized by both spectral methods and single crystal X-ray diffraction studies. The obtained compounds as additives to Bretschneider's solution (trade name Custodiol) were tested on an isolated rat heart, as a classical model for the period of hypothermic ischemia. The experiments showed that adding the synthesized compounds to classical Bretschneider's solution increases the prevention time of the hypoxic injury of the myocardium by at least 45 min of exposure without oxygen supplements and significant histological changes. The "hydrated" forms showed much better results than the parent ones. Meanwhile, it was found that additive activity correlates with the substance's solubility in Custodiol. This data could be a milestone for the further medicinal chemistry project with the goal of developing a new generation of perfusion and flushing compositions for increasing the duration of open heart surgery.

A series of twenty one novel compounds derived from indole-3-acetic acid, the structure of which includes 1,3,4-thiadiazole, thioether, and amide moieties were designed, synthesized, and evaluated for their in vitro antibacterial activity against three bacterial strains. The bioassay results showed that among the synthesized compounds, N-{5-[(2-fluorobenzyl)sulfanyl]-1,3,4-thiadiazol-2-yl}-3-(1H-indol-3-yl)-propanamide demonstrated the best inhibition rate against Pseudomonas syringae pv. actinidiae and N-{5-[(4-chlorobenzyl)sulfanyl]-1,3,4-thiadiazol-2-yl}-3-(1H-indol-3-yl)propanamide possessed the best inhibition rate against Xanthomonas oryzae pv. oryzae and Xanthomonas axonopodis pv. citri, in all cases superior to that of bactericides thiodiazole copper and bismerthiazol.

The reaction of 2-aryl-5-methyl-4-hydroxy-6H-1,3-oxazin-6-ones with 1,3-binucleophilic reagents acetamidine and benzamidine was studied. It was established that in n-propanol under reflux in the presence of sodium n-propoxide or in DMSO, the predominant reaction products were 1,3,5-triazine derivatives. It was shown that the reaction time and the yield of the target product were significantly influenced by the choice of the solvent, the nucleophilicity of the amidine, and the electronic structure of 4 hydroxy-6H-1,3-oxazin-6-one.

This research focuses on the synthesis and in vitro anticancer evaluation of functionalized 2-aryl-5-(4-piperazin-1-yl)oxazoles and 5-[(4-arylsulfonyl) piperazin-1-yl]-2-phenyloxazoles. Oxazoles are a versatile class of compounds with diverse biological activities, making them attractive targets in medicinal chemistry. We incorporated amino and sulfonamide functionalities into the oxazole scaffold, as they have shown potential for interacting with biological targets. The synthesis of target oxazole derivatives was accomplished using 2-aroylamino-3,3-dichloroacrylonitriles as starting materials and employing efficient reaction conditions. The resulting compounds exhibited structural features that make them promising candidates for further chemical modifications and biological evaluations. Additionally, a series of sulfonamides were synthesized from 5-(piperazin-1-yl)oxazole-4-carbonitrile hydrochloride, offering diverse bioactivity and versatile structural characteristics. However, no potent inhibitors of malignant cell growth were identified among the tested compounds. Nevertheless, we categorized the investigated substances into two distinct groups based on their activity profile. Group A, comprising sulfonamides, displayed pronounced anticancer activity against breast cancer and melanoma cell lines. On the other hand, group B, the 2-aryl-5-(4-R-piperazin-1-yl)oxazole-4-carbonitriles, exhibited a moderate effect primarily on renal cancer cell lines. These findings provide valuable insights for further structural modifications in the quest for more potent anticancer agents.

Herein, we present the design, synthesis, and biological activity of novel iminocoumarin imidazo[4,5-b]pyridine derivatives. The prepared compounds were designed to study the type of substituent in position 6 of the coumarin nucleus as well as the type of the substituent at the N atom of imidazo[4,5-b]pyridine core for their effect on the biological activity. Therefore, all compounds were tested for their antiproliferative action on several human cancer cell lines in vitro, for their antioxidative activity, antibacterial activity on several bacterial strains, and for their antiviral activity on several viruses. The results of the evaluation of biological activity revealed that the tested derivatives did not display significant biological activities. The majority of the tested compounds were not active at all, while some derivatives showed low activity in these assays. Therefore, we could conclude that the biological potential of 6-substituted iminocoumarin derivatives is very low – the substitution in position 6 of the coumarin nucleus, in comparison to 7-substituted iminocoumarins, strongly decreases biological activity.

The corresponding pyridyl chalcones were synthesized by the aldol-crotonic condensation of the acetyl derivative of epoxybenzo[7,8]-oxocino[4,3-b]pyridine with aromatic aldehydes. A subsequent cyclization with hydrazine hydrate in acetic acid led to the corresponding 4,5-dihydro-1H-pyrazole derivatives. An assessment of the resulting derivatives for antitubercular activity was carried out.

Functionalized benzofurans are attractive chemical motifs with various pharmacological and physiological applications, therefore chemists are constantly working to develop new and superior methods for their synthesis. During the past decade, significant upsurge of interest can be found in the application of visible-light-mediated chemical reactions for the synthesis of a variety of molecules, including benzofuran derivatives. This would be the first comprehensive review generalizing synthetic methodologies toward functionalized benzofurans under visible-light-assisted conditions. The review will describe different possible visible-light-mediated synthesis and briefly describe the mechanisms of the reactions.

A method for the synthesis of novel 5-methylsulfanylazolo[1,5-a]pyrimidin-7(4H)-ones by heterocyclization of 3-aminoazoles and 5-[bis(methylsulfanyl)methylidene]-2,2-dimethyl-1,3-dioxane-4,6-diones was developed. 5-Methylsulfanyl-7-oxo-4,7-dihydroazolo- [1,5-a]pyrimidine-6-carboxylic acid was isolated during optimization of the process, which allowed us to establish the sequence of transformations of this heterocyclization reaction. The reactivity of the resulting 5-methylsulfanylazolo[1,5-a]pyrimidin-7(4H)-ones in classical electrophilic substitution reactions was studied. The cytotoxic effect of these compounds toward A549, HepG2, and RD tumor cell lines as well as normal HEK-293 cells was assessed.