1,2,3-benzotriazines. IV. The chemical reactivity of benzimidazo[1,2-c] [1,2,3]benzotriazine

The reactions of benzimidazo[1,2-c][1,2,3]benzotriazine (1) with fluoroboric acid, potassium iodide and phenyl isothiocyanate are described. The structure of the phenyl isothiocyanate product is elucidated by chemical and spectroscopic techniques. The reaction of 1 with alcoholic potassium hydroxide is shown to proceed by a free radical mechanism. The structure of the compound formed from 1 and sodium diethyl malonate is investigated by spectroscopic methods. The reduction and photochemical reactivity of 1 are also discussed.     

Design and Synthesis of Some New Biologically Active Indeno[1,2-c]pyrazolones

Russian Journal of General Chemistry - The reaction between different arylhydrazones and ninhydrin (= indene-1,2-3-trione) in acetonitrile at room temperature is described to produce novel...     

1,2,3-Triazolo[4,5-e]-1,2,4-triazolo[3,4-c]pyrimidines

Some new 1,2,3-triazolo[4,5-e]-1,2,4-triazolo[3, 4 -c]pyrimidmes were prepared starting from the corresponding 1,2,3-triazolo[4,5-d]pyrimidines via the formation of the 1,2,4-triazole ring. Thus suitable hydrazino derivatives 6 were condensed with triethyl orthoformate, triethyl orthoacetate and triethyl orthobenzoate to give the expected tricyclic derivatives 7 , 8 and 9 . Intramolecular cyclization of the ethoxycarbonylhydrazino derivatives 10 gave the tricyclic compounds 11 bearing an hydroxyl group in the 3 position. The v-triazolo-s-triazolopyrimidine derivatives were tested towards the A₁ and A_2A adenosine receptors in binding assays, but they did not show any receptor affinity.     

Reduction of Imidazo[4,5-c]pyridine and [1,2,3]Triazolo[4,5-c]pyridine Derivatives to Spinaceamines and 2-Azaspinaceamines

Reduction of 1-substituted [1,2,3]triazolo[4,5-c]pyridines with nickel-aluminum alloy in aqueous alkali gave 2-azaspinaceamines. Reduction of imidazo[4,5-c]pyridine and [1,2,3]triazolo[4,5-c]pyridine derivatives with formic acid in the presence of triethylamine resulted in formation of 5-formylspinaceamines and 2-azaspinaceamines. The 5-formyl group in the latter can be removed by acid hydrolysis. Unsubstituted 2-azaspinaceamine, an aza analog of natural spinaceamine, was synthesized for the first time.     

新型1H-[1,2,3]三氮唑并[4,5-c]哒嗪类化合物的合成

以3,4,6-三氯哒嗪和4-碘吡唑为起始原料,分别与芳胺、碘甲烷、N-Boc哌啶-4-甲磺酸酯和2-(2-溴乙氧基)四氢-2H-吡喃通过取代、氧化和Suzuki等反应,合成了16个新型的1-H-[1,2,3]三氮唑并[4,5-c]哒嗪类化合物,其结构经1H NMR和ESI-MS表征。     

Synthese von Thieno[2,3—d]-1,2,3-triazin- und [1]Benzothieno [2,3—d]-1,2,3-triazin-Derivaten

The title substances, derivatives of two new heterocyclic ring systems, were synthesized by intramolecular cyclisations of diazonium compounds, prepared from derivatives of 2-amino-thiophene-3-carboxamide and of 2-amino-benzo[b]thiophene-3-carboxamide. By-reactions and substitution reactions are mentioned.     

Nucleophilic displacement of aromatic fluorine,Part II Indazoles,indazolo[2,3-c]quinazolines,indazolo[2,3-d] [1,4]benzodiazepines and indazolo[2,3-c]benzo-1,2,3-triazenes

3-(2-Arninophenyl)indazoles 2 were prepared by the reaction of the o-fluorobenzophenones 1 with hydrazines. These indazoles were converted to the tetracyclic title compounds by conventional methods.     

1,2,3-Triazolo[1,5-c]pyrimidine,a novel heterocycle in the polyazaindolizine series

The synthesis and struetural properties of the novel heterocycle 1,2,3-triazolo[1,5-c]pyrimidine are described. No evidence of a triazole-diazoalkylideneazine valence tautomerism process was observed at room temperature.     

Efficient three-step synthesis of benzo[e]imidazo[1,2-c][1,2,3]triazines

A novel three-step sequence toward benzo[e]imidazo[1,2-c][1,2,3]triazine derivatives is investigated. This pathway started from commercially available starting materials afforded 5a–h in good to excellent yields. In this method, we took the advantage of diazonium chemistry, which was followed by intramolecular N-N bond formation in the construction of N-rich cycles.     

Synthesis of new pyrrolo-[3,4-c]isoxazole, pyrrolo[2,3-d]-[1,2,3]triazole, triazolo[4,5-c]-pyridazine, and dipyrrolo-[3,2-b:3′,4′-d]pyran derivatives

New pyrrolo[3,4-c]isoxazole derivatives were synthesized from the key intermediates 4-cyanopyrrolidin-3-ones in two steps. Pyrrolo[2,3-d][1,2,3]triazoles and triazolo[4,5-c]pyridazine were obtained from 2-arylhydrazono-4-cyano-1-(4′-methoxyphenyl)-3-oxopyrrolidines by refluxing with phenylhydrazine in either ethanol or glacial acetic acid. Aldol self-condensation of 1-aryl-4-cyanopyrrolidin-3-ones afforded dipyrrolo-[3,2-b:3′, 4′-d]pyran derivatives. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1841–1848, December, 2007.     

A New Series of Indeno[1,2-c]pyrazoles as EGFR TK Inhibitors for NSCLC Therapy

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death throughout the world. Due to the shortcomings of traditional chemotherapy, targeted therapies have come into prominence for the management of NSCLC. In particular, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy has emerged as a first-line therapy for NSCLC patients with EGFR-activating mutations. In this context, new indenopyrazoles, which were prepared by an efficient microwave-assisted method, were subjected to in silico and in vitro assays to evaluate their potency as EGFR TK-targeted anti-NSCLC agents. Compound 4 was the most promising antitumor agent towards A549 human lung adenocarcinoma cells, with an IC₅₀ value of 6.13 µM compared to erlotinib (IC₅₀ = 19.67 µM). Based on its low cytotoxicity to peripheral blood mononuclear cells (PBMCs), it can be concluded that compound 4 exerts selective antitumor action. This compound also inhibited EGFR TK with an IC₅₀ value of 17.58 µM compared to erlotinib (IC₅₀ = 0.04 µM) and induced apoptosis (56.30%). Taking into account in silico and in vitro data, compound 4 stands out as a potential EGFR TKI for the treatment of NSCLC.     

Amination of anthra [ 1, 9-c,d ] isoxazol-6-ones

The behavior of 3,5-dihalo derivatives of anthra[1, 9-c,d]isoxazol-6-one with respect to primary and secondary amines was studied. 5-Chloroanthra[1,9-c,d]isoxazol-6-one undergoes amination particularly readily. The products of the reaction of isoxazoles with amines are the corresponding amino derivatives. The amination of 5-chloroanthra[1,9-c,d] isoxazol-6-one in refluxing dimethylformamide (DMF) is accompanied by reductive cleavage of the isoxazole ring and the formation of 1-amino-4-arylaminoanthraquinones. Amination in the 5 position with substitution of a hydride ion takes place primarily in the reaction of 3-chloroanthra[1,9-c,d]isoxazol-6-one with benzylamine of cyclohexylamine, whereas the chlorine in the 3 position is replaced by the action of morpholine or piperidine on the same substrate.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 912–915, July, 1980.     

Synthesis of Novel 1,2,3-Triazole-dihydro[3,2-c]chromenones as Acetylcholinesterase Inhibitors

A novel series of 1,2,3-triazole-dihydro[3,2-c]chromenone derivatives were synthesized through an efficient three-step reaction starting from 4-hydroxybenzaldehyde. All the newly synthesized compounds were characterized by infrared and NMR spectroscopy as well as elemental analysis and evaluated for their acetylcholinesterase inhibitory activity.     

Synthesis and antimicrobial of some new substituted tetrazolomethylbenzo[d]-[1,2,3]triazole derivatives using 1H-benzo[d][1,2,3]triazole as starting material

A series of tetrazolomethylbenzo[d][1,2,3]triazole derivatives (2–14) have been synthesized and evaluated as antimicrobial agents from 1H-benzo[d][1,2,3]triazole (1) as starting material. The reaction of benzotriazole 1 with chloroacetonitrile afforded 2-(1H-benzo[d][1,2,3]-triazol-1-yl)acetonitrile 2, which was reacted with sodium azide to give tetrazole derivative 3. Esterification of benzotriazole 1 with ethyl bromoacetate in the presence of anhydrous potassium carbonate afforded ester 4, which was treated with hydrazine hydrate to afford the corresponding hydrazide 5. Reaction of 3 with 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl bromide afforded the nitro-glycoside derivative 6, which was deacetylated using methanolic ammonia to deprotected nitroglycoside 7. The hydrazide 5 was reacted with 4,5,6,7-tetrachlorophthalic anhydride or 1,2,4,5-benzenetetracarboxylic dianhydride in refluxing glacial acetic acid to give the corresponding imides 8 and 9, respectively. Also, the hydrazide 5 was reacted with carbon disulphide in ethanol to give potassium salt 10, which was reacted with hydrazine hydrate to afford aminotriazole derivative 11. The latter compound was reacted with carbon disulphide to afford thiadiazole derivative 12, which was treated with 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl bromide to give the thioglycoside derivative 13. Deacetylation of the thioglycoside 13 using methanolic ammonia solution at room temperature afforded the deprotected thioglycoside 14. The antimicrobial screening of some synthesized compounds showed that many of these compounds have good antimicrobial activities comparable to streptomycin and fusidic acid as reference drugs.