CN108047139B - Chalcone-benzimidazole salt compound and preparation thereof - Google Patents
Chalcone-benzimidazole salt compound and preparation thereof Download PDFInfo
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- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
Abstract
The invention relates to a series of chalcone-benzimidazole salt compounds with a structural general formula (shown as a figure I), which takes 3,4, 5-trimethoxybenzaldehyde and p-hydroxyacetophenone as raw materials and is prepared by the steps of: in a solvent of water=4:1, naOH is used as a catalyst, aldol condensation reaction is carried out to obtain a compound with a chalcone structure, and then the compound is reacted with 1, 3-dibromopropane in ultra-dry DMF at room temperature to obtain a brominated chalcone intermediate. Followed by reaction with benzimidazole, 2-methylbenzimidazole and 5, 6-dimethylbenzimidazole in toluene solvent as Et, respectively 3 N is a catalyst for reaction to synthesize a benzimidazole composition, and then the benzimidazole composition reacts with a bromide in an acetone solvent to synthesize a novel chalcone-benzimidazole salt compound. When the 3-substituent of the 5, 6-dimethyl benzoimidazole is naphthylmethyl, the compound has better in vitro anti-tumor activity.
FIG. I.
Description
Technical Field
The invention relates to a novel chalcone-benzimidazole salt compound and a preparation method thereof, and application of a pharmaceutical composition taking the compound as an active ingredient in anti-tumor aspect.
Background
Malignant tumors are the main killers of current human health, and are one of the most important diseases seriously threatening human life. The comprehensive treatment of tumor mainly includes surgery, radiotherapy and chemotherapy. The medicine plays an important role in malignant tumor chemotherapy and plays an important role in prolonging the survival time of tumor patients and improving the life quality. The newly developed antitumor drug acting on microtubules, namely the tubulin inhibitor, opens up a new place in searching for non-cytotoxic drug targeted therapies, and has a quite important role in clinical treatment of malignant tumors. However, the existing clinically used microtubulin inhibitors have the defects of complex chemical structure, difficult synthesis, easy generation of acquired drug resistance, serious toxic and side effects and the like, and the searching of novel small-molecule microtubulin inhibitors with high efficiency and low toxicity is one of the important points of research in the future. Cancer cells differ most from normal cells in that cancer cells have abnormally frequent and uncontrolled mitosis. Microtubules are the main component of the cytoskeleton and play an important role in maintaining cell morphology, cell division, signal transduction, etc. Because of the important role of microtubules in the process of cell division, tubulin has become one of the important targets for research and development of new anticancer drugs, and tubulin inhibitors acting on the microtubule system have also become an effective antitumor drug.
The mechanism of action of imidazoles such as benzimidazole antiparasitic agents is to selectively bind to tubulin of parasite cells with little effect on tubulin of mammalian host cells. Benzimidazole antiparasitic drugs can be combined with amino acid residue sequences (Ala 63-Lys 103) of the N-terminal region of mammal beta-tubulin to inhibit tubulin polymerization of mammal cells, and have antitumor activity. And the site of binding to mammalian beta-tubulin is different from the previously known tubulin inhibitor binding sites. Based on the above researches, it can be deduced that benzimidazole compounds not only have better tubulin inhibition activity, but also have the advantages of novel action mechanism, simple chemical structure and the like, and can overcome the defects of the tubulin inhibitors clinically used at present to a certain extent.
Therefore, benzimidazole compounds are used as lead compounds, novel chalcone-benzimidazole salt compounds are designed and synthesized, and the microtubulin inhibitor with novel action mechanism, simple chemical structure and remarkable anti-tumor activity is expected to be obtained, so that a new thought is provided for solving the problems of complex chemical structure, easy generation of acquired drug resistance and the like of the traditional microtubulin inhibitor.
Disclosure of Invention
A first object of the present invention is to provide a series of novel chalcone-benzimidazole salt compounds; a second object is to provide a process for the preparation of said novel chalcone-benzimidazole salt compounds; a third object is to provide the application of the novel chalcone-benzimidazole salt compound in anti-tumor aspect.
The invention aims to provide a series of novel chalcone-benzimidazole salt compounds, the structural general formula of which is shown as the following formula:
（Ⅰ）
the structural general formula (I):
when R is 1 = H，R 2 = CH 3 ，R 3 O-bromobenzyl, 2-bromomethylnaphthalene;
when R is 1 = H，R 2 = H，R 3 O-bromobenzyl, 2-bromomethylnaphthalene;
when R is 1 = CH 3 ，R 2 = H，R 3 O-bromobenzyl, 2-bromomethylnaphthalene.
The invention aims to provide a preparation method of a novel chalcone-benzimidazole salt compound, which comprises the following technical routes:
synthetic route for chalcone-benzimidazole salt compound
The preparation method of the novel chalcone-benzimidazole salt compound comprises the following steps:
3,4, 5-trimethoxybenzaldehyde and p-hydroxyacetophenone are used as raw materials, and ethanol is used for preparing the composition by the following steps: in a solvent with water=4:1, sodium hydroxide is used as a catalyst to obtain a compound with a chalcone characteristic structure through aldol condensation reaction, then the compound is dissolved in N, N-dimethylformamide, cesium carbonate is added under the conditions of nitrogen protection and ice bath, and 1, 3-dibromopropane is slowly added dropwise. The bromochalcone intermediate is obtained by reaction at room temperature. Then heating and reacting with benzimidazole, 2-methylbenzimidazole and 5, 6-dimethylbenzimidazole in toluene solvent with triethylamine as a catalyst to synthesize a benzimidazole composition, and reacting with different bromides in acetone solvent to synthesize the novel chalcone-benzimidazole salt compound.
A series of novel chalcone-benzimidazole salt compounds are synthesized, and through in vitro anticancer activity screening, the invention discovers that when the benzimidazole structural unit is 5, 6-dimethyl benzoimidazole and the nitrogen substituent is naphthylmethyl, compared with a commercial anticancer drug cis-platinum (DDP), the novel chalcone-benzimidazole salt compound has better in vitro antitumor physiological activity.
Drawings
FIG. 1 is a technical scheme showing the preparation of novel chalcone-benzimidazole salt compounds of the present invention.
Detailed Description
The present invention will be described in further detail with reference to the drawings and examples, in order to make the objects, technical solutions and advantages of the present invention more apparent. It should be understood that the specific embodiments described herein are for purposes of illustration only and are not intended to limit the scope of the invention.
The preparation method specifically comprises the following steps:
A. preparation of chalcone structural intermediate 1:
in a round bottom flask of 100mL, 3,4, 5-trimethoxybenzaldehyde (7.00 mmol) was dissolved in ethanol: water=4:1 (35 mL) solvent at room temperature, sodium hydroxide (14 mmol) was added, after stirring for 15 minutes, 4-hydroxyacetophenone (8.4 mmol) was added, stirring was performed at room temperature for 24 hours, TLC thin layer chromatography was used to detect the reaction till completion, ethyl acetate extraction, saturated brine washing, combining organic layers, drying over anhydrous magnesium sulfate, evaporating the organic layers under reduced pressure, and separating the concentrate by silica gel chromatography column (petroleum ether: ethyl acetate=1:1) to give compound 1 as a yellow solid (yield: 94%).
B. Preparation of bromoalkane chalcone intermediate 2:
in a 100mL round bottom flask, compound 1 (2.64 mmol) was dissolved in N, N-dimethylformamide (20 mL), cesium carbonate (5.28 mmol) was added under nitrogen protection in an ice bath, and after stirring for 15 minutes, the mixture was slowly warmed to room temperature, stirring was continued for 30 minutes, and then 1, 3-dibromopropane was slowly added dropwise. The reaction was carried out at room temperature for 8 hours, TLC thin layer chromatography was used to monitor the reaction until completion, ethyl acetate extraction was carried out three times, pure water washing, saturated brine washing, combined organic layers, dried over anhydrous magnesium sulfate, and the organic layers were evaporated to dryness under reduced pressure, and the concentrated solution was subjected to silica gel column chromatography (petroleum ether: ethyl acetate=4:1) to give compound 2 as a yellow solid (yield: 82%).
C. Preparation of chalcone-benzimidazole composition:
compound 2 (1.5 mmol) and substituted imidazole (3 mmol) were dissolved in toluene (20 mL) in a 50mL round bottom flask, triethylamine (6 mmol) was added after stirring for 15 min at 110 ℃, reflux was performed for 12-24 hours at 110 ℃, after completion of the reaction by thin layer chromatography, cooled to room temperature, the solvent was distilled off under reduced pressure, ethyl acetate (30 mL ×3) and water were extracted, the organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the solvent was removed under reduced pressure. At this time, the mixed product of the target product and the substituted imidazole is separated, insoluble in ethyl acetate, the filter cake is washed three times with ethyl acetate after filtration, the organic layer is evaporated to dryness under reduced pressure, and the concentrated solution is subjected to silica gel column chromatography (ethyl acetate) to obtain the yellow solid compound 3-5 (yield: 75-81%).
D: preparation of chalcone-benzimidazole salt compounds:
imidazole composition (1 mmol) and halogenated compound (1.2 mmol) are weighed into a 25mL round bottom flask, acetone 10mL is added, stirring reflux is carried out at 60 ℃ for 24-48 hours, solid is separated out, after the reaction is detected to be complete by thin layer chromatography, filtration is carried out, the solid is washed three times by ethyl acetate, and chalcone-benzimidazole salt compound 6-11 is obtained by vacuum drying, and the yield is 75-91%.
Examples of the synthesized compounds
Example 1
Preparation of Compound 6: see preparation method A, B, C, D above:
compound 6 of formula C 37 H 38 Br 2 N 2 O 5。 Yield 79%, yellow solid, melting point 122.4-123.3 ℃ IR (KBr)ν max (cm -1 ): 3450, 2361, 2341, 2027, 1655, 1603, 1460, 1160, 1068, 952, 861, 547. 1 H NMR (400 MHz, DMSO), δ (ppm): 9.76 (1H, s), 8.16 (2H, d, J = 8.7 Hz), 7.90 (2H, d, J = 15.2 Hz), 7.73 (2H, d, J = 5.8 Hz), 7.67 (1H, d, J = 15.5 Hz), 7.40 (2H, t, J = 8.3 Hz), 7.23 (2H, s), 6.97 (2H, d, J = 8.9 Hz), 5.77 (2H, s), 4.72 (2H, t, J = 13.3 Hz), 4.20 (2H, t, J = 11.2 Hz), 3.88 (6H, s), 3.72 (3H, s), 2.51 (6H, d, J = 1.7 Hz), 2.35 (3H, d, J =6.2 Hz). 13 C NMR (100 MHz, DMSO), δ (ppm): 187.74, 162.45, 153.58, 144.20, 142.99, 142.36, 140.11,, 137.47, 137.06, 133.74, 133.25, 133.17, 131.39, 131.37, 131.15, 130.93, 130.81, 130.66, 130.27, 130.19, 130.10, 128.91, 124.34, 124.35, 123.34, 121.61, 114.79, 113.60, 113.65, 106.97, 65.43, 60.62, 56.65, 50.89, 50.74, 44.67, 28.63, 20.48, 20.35. HRMS (ESI-TOF) m/z Calcd for C 37 H 38 Br 2 N 2 O 5 [M-Br] + 669.1964, found 669.1955.
Example 2
Preparation of compound 7: see preparation method A, B, C, D above:
compound 7 of formula C 41 H 41 BrN 2 O 5, Yield 89%, yellow solid, melting point 166.2-166.9 ℃ IR (KBr)ν max (cm -1 ): 3450, 2344, 2027, 1657, 1605, 1564, 1461, 1313, 1272, 1218, 1160, 1068, 952, 861, 548. 1 H NMR (400 MHz, DMSO), δ (ppm): 9.93 (1H, s), 8.14 (1H, d, J = 8.2Hz), 8.06 (1H, s), 7.89 (5H,m), 7.68 (1H, d, J = 15.4 Hz), 7.56 (3H, s), 7.23 (2H, s), 6.95 (2H, d, J = 8.2 Hz), 5.89 (2H, s), 4.71 (2H, s), 4.71 (2H, s), 4.22 (2H, s), 3.88 (6H, s), 3.73 (3H, s), 2.51 (3H, s), 2.34 (6H, d, J = 9.5 Hz). 13 C NMR (100 MHz, DMSO), δ (ppm): 187.74, 162.45, 153.59, 144.19, 141.98, 140.14, 136.90, 133.17, 131.96, 131.35, 131.37, 130.81, 130.42, 129.99, 129.99, 129.24, 128.33, 128.14, 127.86, 127.18, 126.04, 121.63, 114.77, 113.77, 1.6.98, 65.61, 60.62, 56.65, 50.38, 44.75, 28.52, 20.35. HRMS (ESI-TOF) m/z Calcd for C 41 H 41 BrN 2 O 5 [M-Br] + 641.3015, found 641.3008.
Example 3
Preparation of Compound 8: see preparation method A, B, C, D above:
Example 4
Preparation of Compound 9: see preparation method A, B, C, D above:
compound 9 of formula C 40 H 39 BrN 2 O 5, Yield 86%, yellow solid, melting point 231.1-231.8 ℃ IR (KBr)ν max (cm -1 ): 3447, 1655, 1601, 1462, 1262, 1124, 1067, 998, 952, 863, 743, 545, 516. 1 H NMR (400 MHz, DMSO), δ (ppm): 8.10 (3H, d, J = 8.8 Hz), 8.00 (1H, d, J = 9.2 Hz), 7.92 (3H, d, J = 8.8 Hz), 7.87 (2H, t, J = 8.8 Hz), 7.67 (1H, d, J = 15.5 Hz), 7.59 (2H, t, J = 8.9 Hz), 7.53 (2H, t, J = 8.6 Hz), 7.47 (1H, d, J = 8.6 Hz), 7.24 (2H, s), 6.93 (2H, d, J = 8.6 Hz), 6.00 (2H, s), 4.78 (2H, t, J = 12.7 Hz), 4.22 (2H, t, J = 11.3 Hz), 3.87 (6H, s), 3.71 (3H, s), 3.02 (3H, s), 2.41 (2H, t, J = 11.9 Hz). 13 C NMR (100 MHz, DMSO), δ (ppm): 187.72, 162.36, 153.56, 152.74, 144.22, 140.00, 133.17, 132.99, 132.21, 131.57, 131.51, 131.40, 131.11, 130.82, 129.25, 128.27, 128.12, 127.17, 127.06, 126.89, 126.74, 126.69, 126.65, 125.54, 121.55, 114.71, 113.69, 113.59, 106.87, 65.39, 60.62, 56.61, 48.77, 43.13, 28.13, 11.35. HRMS (ESI-TOF) m/z Calcd for C 40 H 39 BrN 2 O 5 [M-Br] + 627.2859, found 627.2852.
Example 5
Preparation of compound 10: see preparation method A, B, C, D above:
compound 10 of formula C 35 H 34 Br 2 N 2 O 5, Yield 84%, yellow solid, melting point 104.2-104.7deg.C; 1 H NMR (400 MHz, DMSO), δ (ppm): 9.93 (1H, s), 8.19 (1H, s), 8.15 (2H, d, J = 8.7 Hz), 7.94 (2H, m), 7.87 (1H, d, J = 8.9 Hz), 7.74 (1H, d, J = 7.8 Hz), 7.68 (2H, d, J = 3.7 Hz), 7.40 (2H, s), 7.37 (1H, d, J = 7.8 Hz), 7.23 (2H, s), 6.94 (2H, d, J = 8.8 Hz), 5.84 (2H, s), 4.77 (2H, t, J = 13.5 Hz), 4.21 (2H, t, J = 11.2 Hz), 3.86 (6H, s), 3.70 (3H, s), 2.45 (2H, t, J = 12.2 Hz). 13 C NMR (100 MHz, DMSO), δ (ppm): 187.70, 162.45, 153.57, 152.82, 144.22, 143.68, 140.05, 133.78, 133.01, 131.84, 131.57, 131.50, 131.37, 131.24, 131.12, 130.81, 128.90, 127.37, 127.25, 123.59, 121.56, 114.86, 114.74, 114.46, 114.27, 107.41, 106.92, 65.55, 60.61, 60.50, 60.23, 56.62, 56.11, 50.92, 46.13, 44.86, 28.59. HRMS (ESI-TOF) m/z Calcd for C 35 H 34 Br 2 N 2 O 5 [M-Br] + 641.1651, found 641.1645.
example 6
Preparation of Compound 11: see preparation method A, B, C, D above:
compound 11 of formula C 39 H 37 BrN 2 O 5, Yield 75%, yellow solid, melting point 99.1-100.2 ℃ IR (KBr)ν max (cm -1 ): 3450, 2345, 1655, 1460, 1160, 1068, 996, 953, 861, 744, 547. 1 H NMR (400 MHz, DMSO), δ (ppm): 10.11 (1H, s), 8.14 (2H, s), 8.11 (2H, d, J = 5.7 Hz), 8.01 (2H, d, J = 17.6 Hz), 7.91 (2H, d, J = 3.1 Hz), 7.88 (2H, d, J = 3.1 Hz), 7.64 (2H, d, J = 7.8 Hz), 7.59 (1H, s), 7.54 (2H, d, J = 2.4 Hz), 7.23 (2H, s), 6.92 (2H, d, J = 8.9 Hz), 5.95 (2H, s), 4.77 (2H, t, J= 14.1 Hz), 4.24 (2H, t, J = 11.0 Hz), 3.87 (6H, s), 3.71 (3H, s), 2.46 (2H, s). 13 C NMR (100 MHz, DMSO), δ (ppm): 187.75, 162.45, 153.58, 144.18, 143.24, 140.67, 133.39, 133.18, 132.61, 131.78, 131.40, 131.37, 130.83, 129.25, 128.34, 128.23, 127.99, 127.18, 126.46, 126.15, 125.90, 125.72, 124.75, 121.65, 114.74, 114.37, 106.98, 65.73, 63.44, 60.62, 56.66, 50.60, 44.93, 28.50 . HRMS (ESI-TOF) m/z Calcd for C 39 H 37 BrN 2 O 5 [M-Br] + 613.2702, found 613.2695.
In vitro antitumor activity cytotoxicity test of novel chalcone-benzimidazole salt compounds
The MTT method is used for researching the in vitro anti-tumor cytotoxicity activity of the synthesized chalcone-benzimidazole salt compound. The in vitro anti-tumor cytotoxic activity study selects five human tumor cell lines of leukemia cells (HL-60), liver cancer cells (SMMC-7721), lung cancer cells (A-549), breast cancer cells (MCF-7) and colon cancer cells (SW 480), uses cisplatin (DDP) as positive control for testing, and uses two-point method to calculate IC of the compound 50 Values.
The test results (Table 1) show that compounds 3-11 have very good in vitro antitumor activity against five human tumor cell lines as compared to the commercial anticancer drug cisplatin (DDP). Compound 7, 9 had better cytotoxic activity against leukemia cells (HL-60) than cisplatin (DDP). The compounds 3,4,5 and 8 have better cytotoxic activity on liver cancer cells (SMMC-7721). Compounds 4, 7 have selective cytotoxic activity against lung cancer cells (a-549). Compounds 4,5, 7 have selective cytotoxic activity against colon cancer (SW 480) cells. Preliminary structure-activity relationship researches show that the 5, 6-dimethyl-benzoimidazole has better in-vitro anti-tumor activity when the 3-substituent of the 5, 6-dimethyl-benzoimidazole is a naphthylmethyl.
TABLE 1 number of antitumor cytotoxic Activity of chalcone-benzimidazole salt CompoundsData (IC) 50 ，μM）
The foregoing description of the preferred embodiments of the invention is not intended to be limiting, but rather is intended to cover all modifications, equivalents, and alternatives falling within the spirit and principles of the invention.
Claims (4)
1. A chalcone-benzimidazole salt compound is characterized in that the structural general formula of the compound is (I):
when R is 1 ＝H，R 2 ＝CH 3 ，
When R is 1 ＝CH 3 ，R 2 ＝H，
2. A process for the preparation of chalcone-benzimidazole salt compounds according to claim 1, characterized in that the process comprises the steps of:
3,4, 5-trimethoxybenzaldehyde and p-hydroxyacetophenone are used as raw materials, and ethanol is used for preparing the composition by the following steps: in a solvent with water=4:1, sodium hydroxide is used as a catalyst to obtain a compound 1 through aldol condensation reaction, then the compound 1 is dissolved in N, N-dimethylformamide, cesium carbonate is added under the conditions of nitrogen protection and ice bath, 1, 3-dibromopropane is slowly added dropwise, and the compound 2 is obtained through reaction at room temperature; then with benzimidazole, 2-methylbenzimidazole or 5, 6-dimethylbenzimidazole in toluene solventSynthesizing a compound 3-5 by heating and reacting ethylamine serving as a catalyst, and reacting with a bromo-compound R on the basis 3 -Br is reacted in an acetone solvent to synthesize a chalcone-benzimidazole salt compound according to claim 1;
3. the method of manufacturing of claim 2, further comprising:
A. preparation of chalcone structural intermediates:
in a 100mL round bottom flask, 7.00mmol of 3,4, 5-trimethoxybenzaldehyde is dissolved in 35mL of solvent with volume ratio of 4:1 ethanol and water at room temperature, 14mmol of sodium hydroxide is added, after stirring for 15 minutes, 8.4mmol of 4' -hydroxyacetophenone is added, stirring is carried out at room temperature for 24 hours, the reaction is detected by thin layer chromatography, ethyl acetate extraction and saturated brine washing are carried out, the organic layers are combined, anhydrous magnesium sulfate is dried, the organic layers are evaporated to dryness under reduced pressure, the concentrated solution is subjected to silica gel chromatographic column separation, and the volume ratio of eluent is 1: petroleum ether and ethyl acetate of 1 to give compound 1 as a yellow solid in yield: 94%;
B. preparation of bromoalkane chalcone intermediates:
in a 100mL round bottom flask, 2.64mmol of compound 1 is dissolved in 20mLN, N-dimethylformamide, 5.28mmol of cesium carbonate is added under the conditions of nitrogen protection and ice bath, stirring is carried out for 15 minutes, then the temperature is slowly raised to room temperature, stirring is continued for 30 minutes, 1, 3-dibromopropane is slowly added dropwise, reaction is carried out at room temperature for 8 hours, thin layer chromatography is carried out to monitor the reaction until the reaction is complete, ethyl acetate is extracted three times, pure water washing, saturated salt water washing, an organic layer is combined, anhydrous magnesium sulfate is dried, the organic layer is evaporated to dryness under reduced pressure, a concentrated solution is separated by a silica gel chromatographic column, and the volume ratio of eluent is 4: petroleum ether and ethyl acetate of 1 to give compound 2 as a yellow solid in yield: 82%;
C. preparation of chalcone-benzimidazole Compounds:
in a 50mL round bottom flask, 1.5mmol of compound 2 and 3mmol of substituted imidazole represented by formula 3-1 are dissolved in 20mL of toluene, 6 mmol of triethylamine is added after stirring for 15 minutes at 110 ℃, reflux is carried out for 12-24 hours at 110 ℃, after the reaction is detected to be complete by thin layer chromatography, cooling to room temperature, evaporating the solvent under reduced pressure, extracting 3 times with 30mL of ethyl acetate and water, merging organic phases, washing with saturated saline, drying with anhydrous sodium sulfate, filtering, decompressing to remove the solvent, at the same time, the mixed product of the target product and the substituted imidazole is separated, insoluble in ethyl acetate, filtering, washing the filter cake with ethyl acetate three times, evaporating the organic layer under reduced pressure, separating the concentrated solution by a silica gel chromatographic column to obtain a yellow solid compound 3-5, yield: 75-81%;
d: preparation of chalcone-benzimidazole salt compounds:
1mmol of the compound 3-5 and 1.2mmol of the halogenide R are weighed out 3 Adding 10mL of acetone into a 25mL round-bottom flask, stirring and refluxing for 24-48 hours at 60 ℃, separating out solids, filtering after the detection reaction of thin layer chromatography is complete, washing the solids with ethyl acetate for three times, and vacuum drying to obtain the chalcone-benzimidazole salt compound according to claim 1, wherein the yield is 75-91%;
4. use of a chalcone-benzimidazole salt compound according to claim 1 in the preparation of an anti-tumor medicament.
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| 吲哚并四氢呋喃-咪唑盐杂合物的合成及细胞毒活性研究;刘正芬，等;《有机化学》;20170120;第1506-1515页 * |
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