2,5,6-tri-substituted primidone derivative and medicine composition containing said derivative
A technology of trisubstituted and pyrimidinone, applied in the field of 2,5,6-trisubstituted pyrimidinone derivatives and pharmaceutical compositions containing said derivatives, to achieve strong anti-HIV-1 virus prevalence, less cytotoxicity, Effect of High Selectivity Index
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Embodiment 1
[0049] Embodiment 1: The general operation of the synthetic reaction of 2-[(substituted alkyl or alkoxycarbonylmethylthio)-6-(substituted arylmethyl)-5-alkyluracil:
[0050] Dissolve 5-alkyl-6-(substituted arylmethyl)-2-thiouracil (3mmol) in 10ml of dry DMF solution, add K 2 CO 3 (3mmol), stirred at room temperature for half an hour, added bromide (3.3mmol), continued to stir the reaction at 40 ° C, TLC traced the disappearance of the raw material point in about 16 hours, stopped the reaction, poured the reaction solution into 50ml of ice water, stirred and precipitated, Filtration, washing the precipitate with water, suction filtration and drying to obtain the crude product, column chromatography or recrystallization to obtain the pure product.
[0051] Using different substituted 5-alkyl-6-(substituted arylmethyl)-2-thiouracil and different α-bromoketones or α-bromohydrocarbyl esters to prepare the target product of formula I respectively by the above method, Some results ...
Embodiment 2
[0111] The general operation of the reaction:
[0112] Under the protection of an inert gas, substituted arylthiophenol (3mmol) and NaOH (3mmol) were stirred at room temperature in 30ml of EtOH for 15 minutes, and the key intermediate (B-3) was added, and the stirring reaction was continued at room temperature, and TLC tracked about After 12 hours, the raw material point disappeared, 10% NaOH solution (12ml) was added, and the reaction was continued to stir at room temperature for 3 hours, concentrated under reduced pressure, added 30ml of water, adjusted to pH=5-6 with dilute hydrochloric acid, CH 2 Cl 2 Extracted, dried, concentrated, purified by column chromatography (PE / EA) or recrystallized to obtain pure product.
[0113] Using differently substituted (B-3) and differently substituted arylthiophenols to obtain the target product by the above method, part of the results are as follows:
[0114]
[0115] Operation as above, separation by column chromatography (PE:EA=1...
Embodiment 3
[0128] Embodiment 3: anti-HIV biological activity test
[0129] The anti-HIV virus activity at the cell level in vitro was determined by the Rega Institute of Pharmacy at Katholleke University in Belgium, mainly including: inhibitory activity and cytotoxicity to HIV-infected MT-4 cells. The method is described as follows: make the compound in HIV-infected MT-4 cells, at different times of HIV infection, use the MTT method to measure the protective effect of the drug on the cytopathic changes induced by HIV, and calculate that 50% of the cells are free from HIV-induced cell changes. half effective concentration IC 50 , the toxicity assay is carried out in parallel with the anti-HIV activity experiment, also in MT-4 cell culture, the concentration (CC 50 ), and calculate the selectivity index SI=CC 50 / IC 50 .
[0130] Materials and Methods:
[0131] The anti-HIV activity of each compound is monitored by the inhibitory effect of the drug on the cytopathic effect caused by H...
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