Journal of Heterocyclic Chemistry最新文献

We have described herein a simple and formal two-step synthesis of 3-(4,6-diaryl-1,3,5-triazin-2-yl)-2-aryl quinolines from 2-chloro-3-(4,6-diaryl-1,3,5-triazin-2-yl) quinolines and boronic acids under the Suzuki–Miyaura conditions. This protocol provides the C-2 arylation of 2-chloro-3-(4,6-diaryl-1,3,5-triazin-2-yl) quinolines under the mild reaction conditions. These newly formed chemo-types may be useful in drug discovery programs or in material chemistry.

A straightforward and efficient method has been developed to access a variety of benzothiazole derivatives via cascade reductive annulation. Iodine mediated, one-pot three-component reaction of o-chloronitroarenes, aryl aldehydes, and elemental sulfur effectively produce benzothiazoles. Moreover, the metal-free strategy allows the facile synthesis of diverse 2-substituted benzothiazoles through multiple carbon–heteroatom bonds in good yields. The present protocol features a greener approach, readily accessible reagents, broad substrate scope, high product yields, and operational simplicity.

A general strategy was developed for the synthesis of new fully decorated 1,2,3-triazoles (4a–4m and 5a–5g) containing quinazolines from 1-(4-nitrophenyl)-2-(quinazolin-8-ylsulfonyl) ethan-1-one and several azides using Ramachary organocatalytic azide-ketone cycloaddition method. This reaction is reported for the synthesis of fully substituted sulfonyl-1,2,3-triazolyl quinazolins at a temperature of 100°C and the yields of the products produced are satisfactory to excellent. In vitro anticancer activity of all these derivatives demonstrated that six compounds, 4d, 4f, 4i, 4j, 5d, and 5e, were effective against two human breast cancer cell lines, MCF-7 and MDA-MB-231. Compounds 4f, 4j, and 5d had more action against both cell lines than Erlotinib. Later, the findings of inhibitory assays of potent compounds 4d, 4f, 4i, 4j, 5d, and 5e against the tyrosine kinase EGFR revealed that compound 5d proved more potent than the reference erlotinib, while 4f and 4j had comparable efficacy. In silico molecular docking studies were also performed on six strong medicines to identify interactions with the EGFR receptor, and the energy estimations were shown to be comparable with the observed IC₅₀ values. Ultimately, using SWISS/ADME and pkCSM, the in silico pharmacokinetic profile of potent compounds 4d, 4f, 4i, 4j, 5d, and 5e was predicted. All of the compounds precisely followed the principles established by Lipinski, Veber, Egan, and Muegge.

Straightforward synthetic access to bis -pyrazole derivatives has presented. The titled bis -pyrazole derivative: 3′,5-diphenyl-1′,2- bis (5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-yl)-1′H,2H-[3,4′- bis pyrazol]-5′-ol 3 was obtained from the reaction of pyran-2,4-dione 1 and 4-hydrazineyl-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine 2 in ethanol in a one-step reaction. The other bis-pyrazole derivative: 5,5′-diphenyl-1′H,2H-[3,4′-bispyrazol]-3′-ol 5 formed from hydrazinolysis of pyran-2,4-dione 1 or (E)-3-((allylamino)(phenyl)methylene)-6-phenyl-2H-pyran-2,4(3H)-dione 4 in ethanol. The molecular structure of both compounds elucidated by X-ray crystallographic identification and spectrophotometric tools. The supramolecular structure of 3 could be described as a hydrogen bonded dimer via O–H…N interactions which are further connected by π…π contacts. Hirshfeld analysis showed the significance of the N…H, O…H, C…H, C…C, N…N, C…O and H…H interactions. These contacts contributed by 14.4%, 3.2%, 16.4%, 3.9%, 1.0%, 0.4% and 42.7%, respectively from the whole interactions occurred in the crystal. The d _norm, shape index and curvedness maps revealed the importance of π–π stacking interactions in the molecular packing where the % C…C is 3.9%. In case of 5, the short N…H, C…H, and H…H contacts contributed by 15.5%–17.0%, 28.3%–36.7% and 37.8%–45%, respectively in the molecular packing.

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.