Mutual prodrug and preparation method based on paclitaxel and nitrogen mustard
A paclitaxel and prodrug technology, applied in the field of new synergistic prodrugs and their preparation, to achieve the effects of improved reaction process, novel structure, and reduced toxicity
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Embodiment 1
[0027] Embodiment 1: The specific synthesis steps of the synergistic prodrug based on paclitaxel-nitrogen mustard of the present invention:
[0028] A. 5-Chloro-2-nitrobenzoic acid (15.02g, 75.4mmol) was dissolved in SOCl 2 (80mL), refluxed for 6 hours; most of the thionyl chloride was evaporated at normal pressure, and the remaining part of the thionyl chloride was removed under reduced pressure to obtain a brown oily 5-chloro-2-nitrobenzoyl chloride crude product, which was added to Diluted with anhydrous tetrahydrofuran; this solution was added dropwise with aniline (7.20g, 78.2mmol) and anhydrous K through a constant pressure funnel at 0°C for 30 minutes 2 CO 3 (10.30g, 75.2mmol) in dry THF (30mL) solution, the reaction mixture continued to stir for 2 hours; after the reaction was over, the solid matter was removed by filtration, and the filtrate was evaporated to remove the solvent under reduced pressure; the crude product was recrystallized in ethyl acetate to obtain A ...
Embodiment 2
[0036] Example 2: Biological activity test of 5-(bis(2-chloroethyl)amino)-2-nitro-N-phenylcarbamoyl-2-aminoethyl-carbonyl paclitaxel
[0037] Specific test process:
[0038] a. Three different tumor cells, LN229, D54MG, and U251MG, were implanted in 96-well plates, 80,000 cells / well, placed at 37°C, 5% CO 2 Cultivate in the incubator for 24 hours;
[0039] b. Add different concentrations of synergistic prodrug (H) and paclitaxel solutions to the cells cultured in step a, and place at 37 ° C, 5% CO 2 Cultivate in the incubator for 2 hours;
[0040] c. Divide the cells in step b into two groups, one of which is set at 37°C, 1%O 2 Cultivate in the incubator for 72 hours, and the other group is placed at 37 ° C, 21% O 2 Cultivate in the incubator for 72 hours;
[0041] d. Add 20 μL of 5 mg / ml MTT solution to each well of the cells cultured in step c, add the solution after 4 hours of action, 100 μL / well, put it in the incubator, and measure it with MK-2 automatic microplate r...
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