CN108530435B - Quinoxaline-containing 1, 4-pentadiene-3-ketone derivative, preparation method and application - Google Patents
Quinoxaline-containing 1, 4-pentadiene-3-ketone derivative, preparation method and application Download PDFInfo
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Abstract
The invention discloses a quinoxaline-containing 1, 4-pentadiene-3-ketone derivative, a preparation method and application thereof, wherein the general formula (I) is as follows:
wherein R is1Is phenyl, substituted phenyl or substituted aromatic heterocyclic radical; r is more than one hydrogen atom, methoxy, nitro, methyl, trifluoromethyl or halogen atom contained in 5, 6, 7 or 8 position in the quinoxaline structure. The compound has excellent inhibitory activity on liver cancer SMMC-7721 cells, shows higher antitumor activity and can be used as a potential antitumor agent.
Description
Technical Field
The invention relates to the technical field of chemical industry, in particular to a quinoxaline-containing 1, 4-pentadiene-3-ketone ether derivative, a preparation method of the quinoxaline-containing 1, 4-pentadiene-3-ketone derivative, and application of the quinoxaline-containing 1, 4-pentadiene-3-ketone derivative in preparing a human liver cancer resistant medicament.
Background
Curcumin, a polyphenol compound derived from turmeric, is widely used as a spice, a food preservative, monosodium glutamate and a dye. 1, 4-pentadiene-3-ketone compound is an important curcumin derivative, which has become an important medical lead and is attracted by people because of having broad-spectrum biological activities of killing insects, inhibiting bacteria, resisting plant viruses, resisting tumors, diminishing inflammation, resisting oxidation and the like. Researches in recent years show that the 1, 4-pentadiene-3-ketone compound has important functions in preventing and treating agricultural diseases and has important application value in the field of medicines.
Xuehei et al (Xuehei, Chenyu, Boehung, Gonghuayu, Liheng, Popule.) study on the synthesis and antitumor Activity of curcumin derivatives containing oxime esters [ J ] St.Mol.Sci, 2013,29(3),198-204.) synthesized a series of asymmetric 1, 5-diaryl-1, 4-pentadiene-3-ketoxime ester compounds, which were found to exhibit a certain inhibitory activity against PC3 cells of prostate cancer cells after 72 hours of treatment at a drug concentration of 10. mu.g/L. Luo et al (Luo, H.; Yang, S.; Cai, Y.; Peng, Z.; Liu, T.Synthesis and biological evaluation of novel 6-chloro-quinazoline derivatives as potential inhibitors [ J ]. Europeanan journal of Medicinal Chemistry,2014,84:746-752.) synthesized a series of quinazoline-containing 1, 4-pentadien-3-one compounds that were found to have certain inhibitory activity against human gastric (MGC-803), human breast (Bcap-37) and prostate (PC3) cancer cells after 72 hours of treatment at a drug concentration of 10. mu.M.
A series of 2-imidazolyl-1, 4-pentadiene-3-ketone derivatives are synthesized by Liuchunli and the like (Liuchunli, Schuman, Liujinyan, Weibingo, Maofei, Yanjie, Li Jian. 2-imidazolyl-1, 4-pentadiene-3-ketone derivatives are synthesized and antibacterial activity research [ J ]. Chinese medicinal chemistry J, 2015,25:15-23.) shows that the compounds have a certain inhibiting effect on staphylococcus epidermidis and staphylococcus aureus. Baldwin et al (Baldwin, P.R.; Reeves, A.Z.; Powell, K.R.; Napier, R.J.; Swimm, A.I.; Sun, A.; Giesler, K.; Bommarius, B.; Shinnick, T.M.; Snyder, J.P.; Liotta, D.C.; Kalman, D.Monocarbyl analogs of current inhibitory growth of anti-inflammatory reactive sensitive and residual peptides of Myco bacterial tulericulosis [ J. ]. European Journal of Medicinal Chemistry 2015 92: 693) designed 8 single carbonyl derivatives that were found to have a superior inhibitory effect on bacterial.
Quinoxaline is an important benzopyrazine heterocyclic compound with aromaticity. Many quinoxaline derivatives have anticancer, antibacterial, etc. activities. Quinoxaline derivatives have been widely used in medicine, agricultural chemicals, dyes, etc., and thus, their synthesis and research have attracted much attention. Therefore, quinoxaline is one of the important resources in the development and research of new drugs in the future, and has a great development prospect.
Disclosure of Invention
The invention aims to overcome the defects and provide the quinoxaline-containing 1, 4-pentadiene-3-ketone derivative which has excellent inhibitory activity on liver cancer SMMC-7721 cells, shows higher antitumor activity and can be used as a potential antitumor agent.
Another object of the present invention is to provide a process for preparing the quinoxaline-containing 1, 4-pentadien-3-one derivatives.
The invention also aims to provide application of the quinoxaline-containing 1, 4-pentadiene-3-ketone derivative in preparing a human liver cancer resistant medicament.
The invention relates to a quinoxaline-containing 1, 4-pentadiene-3-ketone derivative, which has the following general formula:
wherein R is1Is phenyl, substituted phenyl or substituted aromatic heterocyclic radical; r is more than one hydrogen atom, methoxy, nitro, methyl, trifluoromethyl or halogen atom contained in 5, 6, 7 or 8 position in the quinoxaline structure.
The invention relates to a preparation method of quinoxaline-containing 1, 4-pentadiene-3-ketone derivatives, which comprises the following steps:
(1) preparing 2- (hydroxyphenyl) -3-butene-2-one or 4- (hydroxyphenyl) -3-butene-2-one from acetone, salicylaldehyde or 4-hydroxybenzaldehyde under alkaline conditions:
(2) preparing 1-substituted aryl-5- (4-hydroxyphenyl) -1, 4-pentadiene-3-ketone or 1-substituted aryl-5- (2-hydroxyphenyl) -1, 4-pentadiene-3-ketone under alkaline conditions by using substituted aromatic aldehyde, 2- (hydroxyphenyl) -3-buten-2-ketone or 4- (hydroxyphenyl) -3-buten-2-ketone as raw materials:
(3) preparing 2-chloroquinoxaline containing substituent groups by using 2-hydroxyquinoxaline containing substituent groups and phosphorus oxychloride as raw materials:
(4)1- (2-hydroxyphenyl) -5- (substituted aryl) -1, 4-pentadiene-3-ketone and 1- (4-hydroxyphenyl) -5- (substituted aryl) -1, 4-pentadiene-3-ketone are subjected to etherification reaction with 2-chloroquinoxaline containing substituent groups to generate 1, 4-pentadiene-3-ketone derivative containing quinoxaline:
the invention relates to application of quinoxaline-containing 1, 4-pentadiene-3-ketone derivatives in preparation of anti-human liver cancer drugs.
Compared with the prior art, the invention has obvious beneficial effects, and the technical scheme can show that: the invention uses salicylaldehyde and p-hydroxybenzaldehyde to react with acetone for aldol condensation reaction to generate 4- (2-hydroxyphenyl) -3-butylene-2-ketone and 4- (4-hydroxyphenyl) -3-butylene-2-ketone, 4- (2-hydroxyphenyl) -3-butylene-2-ketone and 4- (4-hydroxyphenyl) -3-butylene-2-ketone are subjected to aldol condensation reaction with substituted aromatic formaldehyde to generate 1- (2-hydroxyphenyl) -5- (substituted aryl) -1, 4-pentadiene-3-ketone and 1- (4-hydroxyphenyl) -5- (substituted aryl) -1, 4-pentadiene-3-ketone, 1- (2-hydroxyphenyl) -5- (substituted aryl) -1, 4-pentadiene-3-ketone and 2-chloroquinoxaline containing substituent groups are subjected to etherification reaction to generate 1, 4-pentadiene-3-ketone derivatives containing quinoxaline. Has good inhibitory effect on human liver cancer cell SMMC-7721, and can be used for preparing antitumor agent.
The quinoxaline structure with excellent activity is introduced into the pentadiene ketone structure, so that a series of pentadiene ketone compounds containing quinoxaline in the structure are synthesized, and the synthesized 1, 4-pentadiene-3-ketone compound containing quinoxaline is applied to the aspect of anticancer activity.
Detailed Description
Example 1
Synthesis of 1- (4- (2-quinoxaline-oxy) phenyl) -5- (2-thienyl) -1, 4-pentadien-3-one (compound No. N1), comprising the following steps:
(1) synthesis of 4- (hydroxyphenyl) -3-buten-2-one: 4-hydroxybenzaldehyde (6.1g) was added to 60mL of acetone, stirred for about 15min, and after ice-cooling the reaction system for about 30min, about 100mL of 5% NaOH solution was added to the system, after the dropwise addition, the ice-cooling chamber was removed, and the mixture was stirred at room temperature for about 24 h. And after the reaction is finished, transferring the system into a 500mL beaker, adding a proper amount of ice water, adjusting the pH of the system to be about 5-6 by using a 5% dilute hydrochloric acid solution, separating out a large amount of yellow solid, pumping out the solid, and finally recrystallizing by using an ethanol/water system to obtain the yellow solid with the yield of 68%.
(2) Synthesis of 1- (2-thienyl) -5- (4-hydroxyphenyl) -1, 4-pentadien-3-one: adding 4- (hydroxyphenyl) -3-buten-2-one (4.0g), thiophene-2-formaldehyde (2.86mL) and 50mL of ethanol into a 250mL three-neck flask, stirring for about 30min, adding 60mL of 5% NaOH solution into the system, removing the ice bath chamber after dropwise addition, and stirring at normal temperature for about 24 h. After the reaction is finished, transferring the system to a 500mL beaker, adding a proper amount of ice water, adjusting the pH of the system to be about 5-6 by using a 5% dilute hydrochloric acid solution, separating out a large amount of yellow solid, and extracting the solid to obtain the yellow solid with the yield of 82%.
(3) Synthesis of 2-chloroquinoxaline: 2-hydroxyquinoxaline (2g) and phosphorus oxychloride (20mL) are placed in a 100mL three-necked flask and stirred, 5 drops of DMF are added, the mixture is refluxed for 2 hours, and then the system is transferred to a 500mL beaker and added with a proper amount of ice water. A white solid precipitated, 75% yield.
(4) Synthesis of 1- (4- (2-quinoxaline-oxy) phenyl) -5- (2-thienyl) -1, 4-pentadien-3-one: 1- (2-thienyl) -5- (4-hydroxyphenyl) -1, 4-pentadiene-3-ketone (0.53g), 2-chloroquinoxaline (0.3g), potassium carbonate (0.47g) and acetonitrile (30mL) are stirred uniformly, heated and refluxed, and after about 3-4 h, the reaction is finished, and then the solution is removed and column chromatography is carried out to obtain a yellow solid with the yield of 56%.
Example 2
Synthesis of 1- (4- (2-quinoxaline-oxy) phenyl) -5- (4-methylphenyl) -1, 4-pentadien-3-one (compound No. N2), comprising the following steps:
(1) synthesis of 4- (hydroxyphenyl) -3-buten-2-one: as in step (1) of example 1.
(2) Synthesis of 1- (4-methylphenyl) -5- (4-hydroxyphenyl) -1, 4-pentadien-3-one: the procedure was as in step (2) of example 1, except that 4-methylbenzaldehyde was used as a starting material.
(3) Synthesis of 2-chloroquinoxaline: as in step (3) of example 1.
(4) Synthesis of 1- (4- (2-quinoxaline-oxy) phenyl) -5- (4-methylphenyl) -1, 4-pentadien-3-one: the procedure is as in step (4) of example 1, except that 1- (4-methylphenyl) -5- (4-hydroxyphenyl) -1, 4-pentadien-3-one is used as the starting material.
Example 3
Synthesis of 1- (4- (2-quinoxaline-oxy) phenyl) -5- (3-pyridyl) -1, 4-pentadien-3-one (compound No. N3), comprising the following steps:
(1) synthesis of 4- (hydroxyphenyl) -3-buten-2-one: as in step (1) of example 1.
(2) Synthesis of 1- (3-pyridyl) -5- (4-hydroxyphenyl) -1, 4-pentadien-3-one: the procedure is as in step (2) of example 1, except that pyridine-3-carbaldehyde is used as the starting material.
(3) Synthesis of 2-chloroquinoxaline: as in step (3) of example 1.
(4) Synthesis of 1- (4- (2-quinoxaline-oxy) phenyl) -5- (3-pyridyl) -1, 4-pentadien-3-one: the procedure is as in step (4) of example 1, except that 1- (3-pyridyl) -5- (4-hydroxyphenyl) -1, 4-pentadien-3-one is used as a starting material.
Example 4
Synthesis of 1- (4- (2-quinoxaline-oxy) phenyl) -5- (2-pyridyl) -1, 4-pentadien-3-one (compound No. N4), comprising the following steps:
(1) synthesis of 4- (hydroxyphenyl) -3-buten-2-one: as in step (1) of example 1.
(2) Synthesis of 1- (2-pyridyl) -5- (4-hydroxyphenyl) -1, 4-pentadien-3-one: the procedure is as in step (2) of example 1, except that 2-pyridinecarboxaldehyde is used as the starting material.
(3) Synthesis of 2-chloroquinoxaline: as in step (3) of example 1.
(4) Synthesis of 1- (4- (2-quinoxaline-oxy) phenyl) -5- (2-pyridyl) -1, 4-pentadien-3-one: the procedure is as in step (4) of example 1, except that 1- (2-pyridyl) -5- (4-hydroxyphenyl) -1, 4-pentadien-3-one is used as a starting material.
Example 5
Synthesis of 1- (4- (2-quinoxaline-oxy) phenyl) -5- (4-methoxyphenyl) -1, 4-pentadien-3-one (compound No. N5), comprising the following steps:
(1) synthesis of 4- (hydroxyphenyl) -3-buten-2-one: as in step (1) of example 1.
(2) Synthesis of 1- (4-methoxyphenyl) -5- (4-hydroxyphenyl) -1, 4-pentadien-3-one: the procedure is as in (2) of example 1, except that 4-methoxybenzaldehyde is used as a starting material.
(3) Synthesis of 2-chloroquinoxaline: as in step (3) of example 1.
(4) Synthesis of 1- (4- (2-quinoxaline-oxy) phenyl) -5- (4-methoxyphenyl) -1, 4-pentadien-3-one: the procedure is as in step (4) of example 1, except that 1- (4-methoxyphenyl) -5- (4-hydroxyphenyl) -1, 4-pentadien-3-one is used as the starting material.
Example 6
Synthesis of 1- (4- (2-quinoxaline-oxy) phenyl) -5- (2-methoxyphenyl) -1, 4-pentadien-3-one (compound No. N6), comprising the following steps:
(1) synthesis of 4- (hydroxyphenyl) -3-buten-2-one: as in step (1) of example 1.
(2) Synthesis of 1- (2-methoxyphenyl) -5- (4-hydroxyphenyl) -1, 4-pentadien-3-one: as in example 1 No
(2) The difference is that 2-methoxy benzaldehyde is used as raw material.
(3) Synthesis of 2-chloroquinoxaline: as in step (3) of example 1.
(4) Synthesis of 1- (4- (2-quinoxaline-oxy) phenyl) -5- (2-methoxyphenyl) -1, 4-pentadien-3-one: the procedure is as in step (4) of example 1, except that 1- (2-methoxyphenyl) -5- (4-hydroxyphenyl) -1, 4-pentadien-3-one is used as the starting material.
Example 7
Synthesis of 1- (4- (2-quinoxaline-oxy) phenyl) -5- (4-chlorophenyl) -1, 4-pentadien-3-one (compound No. N7), comprising the following steps:
(1) synthesis of 4- (hydroxyphenyl) -3-buten-2-one: as in step (1) of example 1.
(2) Synthesis of 1- (4-chlorophenyl) -5- (4-hydroxyphenyl) -1, 4-pentadien-3-one: the procedure is as in (2) of example 1, except that 4-chlorobenzaldehyde is used as the starting material.
(3) Synthesis of 2-chloroquinoxaline: as in step (3) of example 1.
(4) Synthesis of 1- (4- (2-quinoxaline-oxy) phenyl) -5- (4-chlorophenyl) -1, 4-pentadien-3-one: the procedure is as in step (4) of example 1, except that 1- (4-chlorophenyl) -5- (4-hydroxyphenyl) -1, 4-pentadien-3-one is used as the starting material.
Example 8
Synthesis of 1- (4- (2-quinoxaline-oxy) phenyl) -5- (2, 4-dimethoxyphenyl) -1, 4-pentadien-3-one (compound No. N8) comprising the following steps:
(1) synthesis of 4- (hydroxyphenyl) -3-buten-2-one: as in step (1) of example 1.
(2) Synthesis of 1- (2, 4-dimethoxyphenyl) -5- (4-hydroxyphenyl) -1, 4-pentadien-3-one: the procedure is as in step (2) of example 1, except that 2, 4-dimethoxybenzaldehyde is used as a starting material.
(3) Synthesis of 2-chloroquinoxaline: as in step (3) of example 1.
(4) Synthesis of 1- (4- (2-quinoxaline-oxy) phenyl) -5- (2, 4-dimethoxyphenyl) -1, 4-pentadien-3-one: the procedure is as in step (4) of example 1, except that 1- (2, 4-dimethoxyphenyl) -5- (4-hydroxyphenyl) -1, 4-pentadien-3-one is used as starting material.
Example 9
Synthesis of 1- (4- (2-quinoxaline-oxy) phenyl) -5- (4-fluorophenyl) -1, 4-pentadien-3-one (compound No. N9) comprising the following steps:
(1) synthesis of 4- (hydroxyphenyl) -3-buten-2-one: as in step (1) of example 1.
(2) Synthesis of 1- (4-fluorophenyl) -5- (4-hydroxyphenyl) -1, 4-pentadien-3-one: the procedure is as in step (2) of example 1, except that 4-fluorobenzaldehyde is used as the starting material.
(3) Synthesis of 2-chloroquinoxaline: as in step (3) of example 1.
(4) Synthesis of 1- (4- (2-quinoxaline-oxy) phenyl) -5- (4-fluorophenyl) -1, 4-pentadien-3-one: the procedure is as in step (4) of example 1, except that 1- (4-fluorophenyl) -5- (4-hydroxyphenyl) -1, 4-pentadien-3-one is used as a starting material.
Example 10
Synthesis of 1- (4- (2-quinoxaline-oxy) phenyl) -5-phenyl-1, 4-pentadien-3-one (compound No. N10), comprising the following steps: (1) synthesis of 4- (hydroxyphenyl) -3-buten-2-one: as in step (1) of example 1.
(2) Synthesis of 1-phenyl-5- (4-hydroxyphenyl) -1, 4-pentadien-3-one: as in example 1 (2)
The difference is that benzaldehyde is used as a raw material.
(3) Synthesis of 2-chloroquinoxaline: as in step (3) of example 1.
(4) Synthesis of 1- (4- (2-quinoxaline-oxy) phenyl) -5-phenyl-1, 4-pentadien-3-one: the procedure is as in step (4) of example 1, except that 1-phenyl-5- (4-hydroxyphenyl) -1, 4-pentadien-3-one is used as a starting material.
The physicochemical properties of the synthesized quinoxaline-containing 1, 4-pentadien-3-one derivatives are shown in Table 1, and the data of hydrogen nuclear magnetic resonance (1H NMR) and carbon spectrum (13C NMR) are shown in Table 2.
TABLE 1 physicochemical Properties of the target Compounds
TABLE 2 NMR and C spectra data for target compounds
Antitumor Activity of the above target Compound
Test method
A. Culturing cell strain and treating medicament: culturing human liver cancer SMMC-7721 cells in RPMI 1640 culture medium containing 10% FBS at 37 deg.C in saturated humidity incubator containing 5% CO2, changing liquid every other day, and passaging for 1-2 days. Compounds were dissolved in DMSO as stock solutions. Before use, it is diluted to the desired concentration directly with the culture medium. The blank control group is added with DMSO with the same volume as the drug, and the positive control group is added with gemcitabine with the same concentration as the tested drug. The final concentration of DMSO in the treatment formulation did not exceed 0.1% (V/V).
The principle of the screening experiment of the in vitro anti-tumor drug by the MTT colorimetric method: MTT is a dye that accepts hydrogen ions, and acts on the respiratory chain in mitochondria of living cells, and the tetrazole ring is cleaved by succinate dehydrogenase and cytochrome c to produce blue-purple formazan crystals. Formazan crystals are produced in an amount proportional to the number of living cells, while dead cells do not have this function. The crystal can be dissolved by dimethyl sulfoxide and SDS, and the absorbance at 595nm can be measured by an enzyme-linked immunosorbent assay, so that the number of living cells can be indirectly reflected. Within a certain cell range, the amount of MTT-forming crystals is proportional to the number of cells. The method can be used for large-scale screening of anti-tumor drugs, cytotoxicity experiments, tumor radiosensitivity determination and the like.
Screening experiment steps of the in vitro anti-tumor drug by MTT colorimetric method: the upper and lower rows of the 96-well plate were sealed with sterilized secondary water at 200. mu.L per well. Cells in logarithmic growth phase were taken, after conventional digestion, resuspended in RPMI 1640 medium containing 10% FBS, and seeded at a final concentration of 4X 104/mL in 96-well culture plates, 100. mu.L per well, and the rightmost column was blank control, plus cell-free RPMI 1640 medium with serum. The cells are placed in a saturated humidity incubator with the temperature of 37 ℃ and the CO2 of 5 percent for 24 hours to adhere to the wall. The medium was aspirated off, and serum containing medium at different drug concentrations was added at 200. mu.L per well, taking care that the final DMSO concentration in the medium did not exceed 0.1%, and 200. mu.L of complete medium was added per well in the blank control. The required time for the experiment was treated separately, the supernatant removed and MTT at 100. mu.L/well concentration 0.5mg/mL added. After 4h of incubation, the cells were supplemented with 100. mu.L/well of 10% SDS. Dissolving the crystal at 37 deg.C for 10 hr, taking out, slightly shaking for 5min, standing at room temperature for 30min, measuring OD value at A595 wavelength, and calculating cell activity, inhibition rate and P value.
The curve is plotted with the drug concentration or treatment time on the horizontal axis and the OD value or inhibition ratio on the vertical axis. Six wells were repeated for each sample concentration, three times for each experiment, and the average was taken as the final result.
The experimental result is analyzed by variance with SPSS software, and the difference is significant when p is less than 0.05 and is extremely significant when p is less than 0.01. The inhibition rate of cell proliferation is calculated as follows:
TABLE 3 in vitro inhibition rate of target compounds on liver cancer SMMC-7721 cells for 72h
The inhibitory activity of the target compound on the SMMC-7721 cells of the liver cancer was tested by the MTT method with the commercial drug gemcitabine as a positive control at test concentrations of 1. mu.M and 10. mu.M (see Table 3). The test results show that: most target compounds have good inhibitory activity on liver cancer SMMC-7721 cells. When the concentration is 10 mu M, the activity inhibition range of the series of compounds (except compounds N5 and N7) on the liver cancer SMMC-7721 cells is 69.09% -100.00%, wherein the activity inhibition of the compound N3 on the liver cancer SMMC-7721 cells reaches 100.00%, and is far better than that of a control medicament gemcitabine (42.52%); when the concentration is 1 mu M, the series of compounds have good inhibitory activity on liver cancer SMMC-7721 cells, and the inhibitory rate is higher than that of a control medicament gemcitabine (20.16%). Especially, the compounds N3 and N4 have excellent inhibitory activity on liver cancer SMMC-7721 cells, and the inhibitory activity is more than 90.00 percent and far better than gemcitabine (20.16 percent).
In order to further understand the anticancer activity of the compounds, the morphology of the liver cancer SMMC-7721 cells under an electron microscope is researched, and the morphology of the liver cancer SMMC-7721 cells after 24, 48 and 72 hours of medicament treatment is recorded by an inverted microscope, wherein the data show that: the compounds have obvious inhibition effect on the activity of liver cancer SMMC-7721 cells. The inhibitory activity of some compounds was higher than that of the positive drug gemcitabine at the same dose and duration of action (see table 3). It is worth mentioning that commercial drugs, i.e. positive drugs, have significantly high toxicity to tumor cells (such that the cells are completely crushed and lysed), while the compound synthesized by the invention has an inhibitory effect on tumor cells at low concentration and has little damage to target cells, and the inhibitory activity is mainly reflected in inhibiting proliferation of cells (the number of cells is significantly reduced compared with that of a control), or inducing cell differentiation (from morphological observation, we can easily find that the cells are deformed while the number of the cells is reduced, but the damage is not significant), but the inhibitory activity is significantly enhanced as the concentration of the compound is increased overall. Wherein the partial compound has excellent inhibitory activity on liver cancer SMMC-7721 cells, and can be used as potential antitumor agent.
The above description is only a preferred embodiment of the present invention, and is not intended to limit the present invention in any way, and any simple modification, equivalent change and modification made to the above embodiment according to the technical spirit of the present invention are within the scope of the present invention without departing from the technical spirit of the present invention.
Claims (1)
1. An application of 1, 4-pentadiene-3-ketone derivative containing quinoxaline in preparing anti-human liver cancer drugs;
the quinoxaline-containing 1, 4-pentadiene-3-ketone derivative is as follows:
1- (4- (2-quinoxaline-oxy) phenyl) -5- (2-thienyl) -1, 4-pentadien-3-one;
1- (4- (2-quinoxaline-oxy) phenyl) -5- (4-methylphenyl) -1, 4-pentadien-3-one;
1- (4- (2-quinoxaline-oxy) phenyl) -5- (3-pyridyl) -1, 4-pentadien-3-one;
1- (4- (2-quinoxaline-oxy) phenyl) -5- (2-pyridyl) -1, 4-pentadien-3-one;
1- (4- (2-quinoxaline-oxy) phenyl) -5- (4-methoxyphenyl) -1, 4-pentadien-3-one;
1- (4- (2-quinoxaline-oxy) phenyl) -5- (2-methoxyphenyl) -1, 4-pentadien-3-one;
1- (4- (2-quinoxaline-oxy) phenyl) -5- (4-chlorophenyl) -1, 4-pentadien-3-one;
1- (4- (2-quinoxaline-oxy) phenyl) -5- (2, 4-dimethoxyphenyl) -1, 4-pentadien-3-one;
1- (4- (2-quinoxaline-oxy) phenyl) -5- (4-fluorophenyl) -1, 4-pentadien-3-one;
1- (4- (2-quinoxaline-oxy) phenyl) -5-phenyl-1, 4-pentadien-3-one.
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| CN109824610B (en) * | 2019-04-02 | 2022-04-19 | 贵州大学 | Chalcone derivative containing quinoxaline, preparation method and application thereof |
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