Syntheses of 5‐alkylthio‐1,3‐diaryl‐1,2,4‐triazoles

Arylation of the readily available 3‐alkythio‐5‐aryl‐1,2,4‐triazoles gave 5‐alkylthio‐1,3‐diaryl‐1,2,4‐triazoles in moderate yield. The structures of the latter were confirmed by NOE and ¹³C‐NMR.     

Selenium heterocycles. XXIX. Reaction of substituted 2-thioxo-1,3-thiaselenoles with ethyl diazoacetate,ethyl azidoformate and phenyl azide

Reaction of 5-substituted 2-thioxo-1,3-thiaselenoles with ethyl diazoacetate, phenyl azide and ethyl azidoformate afforded 2-substituted ω-carbethoxy-1,4-thiaselenafulvenes (II) , 5-substituted 2-phenylimino-1,3-thiaselenoles (IV) and 5-substituted 2-carbethoxyimino-1,3-thiaselenoles (V) , respectively. The structure of these compounds were confirmed by spectroscopic methods and chemical analysis.     

Syntheses of [1,2,3]selenadiazolo[4,5‐e]benzofuran or benzothiophene, [1,2,3]thiadiazolo[4,5‐e]benzofuran or benzothiophene,and 2‐benzofuranyl‐1,3,4‐oxodiazole derivatives

Dehydrogenation of ethyl 3‐methyl‐4‐oxo‐4,5,6,7‐tetrahydrobenzofuran‐2‐carboxylate 1 with 2,2′‐azobi‐sisobutyronitrile and N‐bromosuccinimide gave ethyl 4‐hydroxy‐3‐methylbenzofuran‐2‐carboxylate 3 . Reaction of compounds 3–4 with hydrazine hydrate afforded the corresponding hydrazides 5a‐b . The reaction of 5a‐b with aldehydes yielded substituted hydrazones 6a‐l . Compounds 7a‐d were prepared from compounds 6a‐d and bromine in acetic acid. Lead tetraacetate oxidation of compounds 6e‐l afforded substituted oxadiazoles 8e‐l . Selenium dioxide oxidation of 4‐oxo‐4,5,6,7‐tetrahydrobenzofuran semicarbazones 9, 14a and 4‐oxo‐4,5,6,7‐tetrahydrobenzothiophene 14b gave the tricyclic 1,2,3‐selenadiazoles 10, 15a and 15b respectively. Reaction of semicarbazones 9, 14a and 14b with thionyl chloride afforded the corresponding 1,2,3‐thiadiazoles 12, 16a and 16b respectively.     

Selenium heterocycles. XLI . Syntheses of substituted thiazolo,selenazolo, 1,2,3-thiadiazolo and 1,2,3-selenadiazoloquinolines

The reaction of thionyl chloride with the semicarbazone 2 gave 4,5-dihydro[1,2,3]thiadiazolo[4,5-f]quinoline. Selenium dioxide oxidaion of compound 2 gave 4,5-dihydro[1,2,3]selenadiazolo[4,5-f]quinoline ( 4 ) and the aromatic analog 5 . Thermolysis of compound 5 yielded [1,4]diselenino[2,3-f:5,6-f′]diquinoline ( 6 ). Reaction of selenourea with α-bromoketone 7 gave 2-amino-4,5-dihydroselenazolo[4,5-f]quinoline ( 8 ). Compounds 9 and 10 were prepared from the reaction of selenobenzamide and thiobenzamide with compound 7 .     

Synthesis of 3-formylbenzo[b]furan and 1-methyl-3,4-dihydrobenzo[b]-furo[2,3-c]pyridine

Starting from the readily available 3-methylcoumarilate, 3-formylbenzo[b]furan was synthesized in high yield. The latter could be converted to 1-methyl-3,4-dihydrobenzo[b]furo-[2,3-c]pyridine in moderate yield.     

Synthesis and calcium channel antagonist activities of new derivatives of dialkyl 1,4-dihydro-2,6-dimethyl-4-(5-phenylisoxazol-3-yl)pyridine-3,5-dicarboxylates

The new analogues of nifedipine, in which 2-nitrophenyl group at position 4 is replaced by phenylisoxazolyl substituent, were synthesized. The symmetrical dialkyl 1,4-dihydro-2,6-dimethyl-4-(5-phenylisoxazol-3-yl)pyridine-3,5-dicarboxylates were prepared by classical Hantzsch condensation, and the asymmetrical analogues were synthesized using a procedure reported by Dagnino that involved the condensation of alkyl acetoacetate with alkyl 3-aminocrotonate and 5-phenylisoxazole-3-carboxaldehyde. The structure of all compounds was confirmed by IR, ¹H NMR and Mass spectra. In vitro calcium channel antagonist activities were evaluated as calcium channel antagonists using the high K⁺ concentration of guinea-pig ileum longitudinal smooth muscle (GPILSM) assay. These compounds exhibited moderate calcium antagonist activity (IC₅₀ = 10^?7 to 10^{? 5} M range) relative to the reference drug nifedipine (IC₅₀ = 1.10 ± 0.40 × 10^?8 M).     

Syntheses of substituted-1,2,4-triazoles

Starting from the readily available 3-phenylpropionitrile, 3-(or 5-)(2-phenethyl)-1,2,4-triazole 3 was prepared. Reaction of compounds 3 with diazomethane afforded 1-methyl-3-(2-phenethyl)-1,2,4-triazole (4) and 1-methyl-5-(2-phenethyl)-1,2,4-triazole (5) . Reaction of compound 3 with methanesulfonyl chloride, benzenesulfonyl chloride or p-toluenesulfonyl chloride afforded only one of the expected isomer; namely compounds 6 , 7 and 8 respectively.     

Synthesis and Cytotoxic Evaluation of Novel 1,2,3‐Triazole‐4‐Linked (2E,6E)‐2‐Benzylidene‐6‐(4‐nitrobenzylidene)cyclohexanones

This work describes the synthesis of novel 1,2,3‐triazole‐4‐linked (2E,6E)‐2‐benzylidene‐6‐(4‐nitrobenzylidene)cyclo‐hexanones starting from cyclohexanone. 1‐(Cyclohex‐1‐en‐1‐yl)piperidine, the enamine from cyclohexanone and piperidine, reacted with 4‐nitrobenzaldehyde to obtain 2‐(4‐nitrobenzylidene)cyclohexanone. Condensation of the latter compound with (prop‐2‐yn‐1‐yloxy)benzaldehyde derivatives under acidic conditions gave (4‐nitrobenzylidene)‐[(prop‐2‐yn‐1‐yloxy)‐benzylidene]cyclohexanones. Finally, ‘click reaction’ of these derivatives and various organic azides led to the title compounds. All compounds were examined by MTT assay for cytotoxic activity in one human breast cancer cell line, MDA‐MB‐231.