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Synthesis and anti-integrase evaluation of novel calix[4]arene derivatives containing the triazolyl 1,3-diketo moiety

Synthesis and anti-integrase evaluation of novel calix[4]arene derivatives containing the triazolyl 1,3-diketo moiety
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摘要 A series of novel calix[4]arene derivatives incorporating two triazolyl 1 3-diketo subunits in alternate positions at the lower rim were synthesized and screened for HⅣ integrase inhibition activity.The chemical structures of these compounds were confirmed by means of1H NMR 13C NMR,and ESI-MS.Preliminary bioassays indicated that calix[4]arene derivatives proved to be more active than p-tertbutylcalix[4]arene derivatives.In particular,compound 4g presented the most potent integrase strand transfer inhibitory activity with an IC50value of 6.1 mmol/L. A series of novel calix[4]arene derivatives incorporating two triazolyl 1 3-diketo subunits in alternate positions at the lower rim were synthesized and screened for HⅣ integrase inhibition activity.The chemical structures of these compounds were confirmed by means of1H NMR 13C NMR,and ESI-MS.Preliminary bioassays indicated that calix[4]arene derivatives proved to be more active than p-tertbutylcalix[4]arene derivatives.In particular,compound 4g presented the most potent integrase strand transfer inhibitory activity with an IC50value of 6.1 mmol/L.
出处 《Chinese Chemical Letters》 SCIE CAS CSCD 2014年第5期737-740,共4页 中国化学快报(英文版)
基金 the National Natural Science Foundation of China (Nos.21102003, 21102084, 81202438) Scientific Research Foundation for the Introduction of Talent and Young Teachers Scientific Research Foundation of Anhui University of Science & Technology (Nos. 11214, 2012QNY27) for the financial supports
关键词 HIV-1 integrase inhibitor arene derivative 1 2 3-Triazole 1 3-Diketo Strand transfer HIV-1 integrase inhibitor Calix[4]arene derivative 1 2 3-Triazole 1 3-Diketo Strand transfer
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  • 9General procedure for the preparation of 3: 4-nitrobenzene sulfonamide 2 were dissolved in EtOAc (50-100 mL) and SnCl2-2H2O (1.125 g per mmol nitro compound) was added. The mixture was heated under reflux for 4 h. Then, NaHCO3 solution was added until pH 7-8 was reached and the organic layer was separated. The aqueous layer was extracted three times with EtOAc. The combined organic layers were washed with brine and dried over MgSO4. Then, the solvent was removed in vacuo to obtain the crude products. General procedure for the preparation of 4: a mixture of diethyl ethoxymethylenemalonate (46 mmol) and 4-aminobenzene sulfonamide 3 (46 mmol) in 1,4-dioxane solution (25 mL) was refluxed for 3.5 h until the reaction was finished (monitor by thin lay chromatography). Then the solvent was removed under reduced pressure and the residue was recrystallized from Petroleum ether to obtain the pure products. General procedure for the preparation of 5: phenyl ether (40 mL) was heated under stirring at 250 ℃ containing catalytic p-chlorobenzoic acid. The aminomethylenemalonate 4 (10 mmol) was slowly added, and the resulting mixture was remained the temperature at 250 ℃ for 0.5 h. After the mixture was cooled at room temperature, the resulting precipitate was collected by filtration, washed with petroleum ether, and re.crystallized from DMF to provide quinolone 5. General procedure for the preparation of 6: quinolone 5 (1 mmol) was dissolved in the mixed solution of EtOH/H2O (25 mL) and NaOH ( 1.1 mmol) was added. The mixture was refluxed for 1 h. Removal of the solvents under reduced pressure and acidification with 10% H2SO4 gave a solid, which was washed with water, dichloromethane and dried. The resulting quinoline-3-carboxylic acid 6 was recrystallized from the appropriate solvent.
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