CN102344351B - Aryl-substituted chalcones compound, its preparation method and its application - Google Patents
Aryl-substituted chalcones compound, its preparation method and its application Download PDFInfo
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Abstract
The invention discloses an aryl-substituted chalcones compound, a preparation method and an application. The aryl-substituted chalcones compound has a structure shown as a formula(I) or a formula(II), wherein, R1, R2, R3, R4, R5 are aromatic groups or aromatic groups with a substituent, the aromatic groups are phenyl, furan, thienyl, pyridyl, pyrimidyl, thiazolyl or pyrrolyl, the substituent is one or more selected from hydroxyl, methoxyl, ethoxyl, methyl, ethyl, trifluoromethyl, halogen, amino, methylamino or dimethylamino; R3 is selected from hydrogen, amino or-NHCOCH3. The aryl-substituted chalcones compound introduces the aromatic groups based on a phenyl skeleton to form a structure with steric hindrance, the molecule presents a V-shaped spatial conformation, compared with the current chalcone compounds, and the aryl-substituted chalcones compound has higher inhibitory activity to cancer cells and can be used for preparing the antitumor drugs.
Description
Technical field
The invention belongs to the synthetic field of medicinal design, be specifically related to a kind of aryl and replace chalcone compounds and its preparation method and application.
Background technology
Chalcone compounds extensively is present in occurring in nature, and its basic skeleton structure is 1,3-diphenylprop ketenes.Research is at present found to introduce various substituting groups on basic skeleton structure, physiology and the pharmaceutical activity that can make the chalcone compounds performance make new advances.The existing activity about chalcone compounds comprises anti-inflammatory activity, anti-angiogenic proliferative activity, antimicrobial acivity, anti-microbial activity, optical recording material, thymoleptic, agricultural chemicals, antitumor etc.As Chinese patent CN200710037570.8 discloses the chalcone compounds that having of a type suppressed tumour or suppressed the cell hyperproliferation effect.
The dibenzyl structure is a kind of pharmacophoric group (as Biphenylylmethylcarbinol) be present in natural product, and the existing multiple dibenzyl structure antineoplastic compound that contains is shown in bibliographical information.
Colchicine is that a kind of inhibition tubulin is assembled, and causes the natural product of tumour cell G2/M phase Cycle Arrest, has excellent anti-tumor activity, and its space structure be the analysis showed that, it is a kind of " V " font conformation.Antitumor Natural Products with similar effect also has CA4 etc., and they all have " V " font conformation, and existing this special conformation of multiple analog designs synthetic antineoplastic compound and sees bibliographical information.
But the anti-tumor activity of current chalcone compounds is still lower, we wish by introducing aryl on chalcone skeleton, change space conformation wherein, design a kind of " merging shape " molecule, and make this quasi-molecule present a kind of " V " figure space conformation, thereby it is synthetic simple to obtain a class, there is the chalcone compounds of excellent anti-tumor activity.
Summary of the invention
Goal of the invention of the present invention is to provide a kind of aryl to replace chalcone compounds, and this compound has high anti-tumor activity, can be applied to the preparation of antitumor drug.
Another object of the present invention is to provide described aryl to replace the preparation method of chalcone compounds.
Another object of the present invention is to provide described aryl to replace the application of chalcone compounds.
Above-mentioned purpose of the present invention is achieved by following technical solution:
Aryl replaces chalcone compounds, has suc as formula structure shown in (I) or formula (II):
Wherein, R
1, R
2, R
4, R
5for the aromatic series group or containing substituent aromatic series group, described aromatic series group is phenyl, furyl, thienyl, pyridyl, pyrimidyl, thiazolyl or pyrryl, described substituting group is hydroxyl, methoxyl group, oxyethyl group, methyl, ethyl, trifluoromethyl, halogen, amino, any one or a few in methylamino or dimethylin; R
3be selected from hydrogen, amino or-NHCOCH
3.
As a kind of preferred version, described aromatic series group is preferably phenyl.
As a kind of preferred version, described halogen is preferably fluorine, chlorine or bromine; As a kind of more preferably scheme, described halogen is fluorine more preferably.
As a kind of preferred version, in formula (I), described R
4be preferably the phenyl ring that bromine, chlorine, methoxyl group and/or hydroxyl replace, described R
5be preferably the phenyl ring that fluorine replaces.
As a kind of preferred version, in formula (II), R
1the phenyl ring that is preferably furan nucleus, thiphene ring or is replaced by fluorine, bromine, methoxyl group and/or hydroxyl, R
2be preferably phenyl ring or the pyridine ring of fluorine or methoxy substitution.
Described aryl replaces the preparation method of chalcone compounds, mainly comprises the formation of cinnamophenone structure and replace aromatic ring introducing two portions, with R in formula (I) or formula (II) compound
3be example during=H, specifically comprise the steps:
Take adjacent bromoacetophenone or a bromoacetophenone is raw material, in potassium hydroxide-ethanol solution with by R
1or R
4the formaldehyde reaction replaced, obtain intermediate product A, described intermediate product A under palladium catalyst, alkaline solution, solvent exist with R
2or R
5the boric acid microwave heating reaction replaced, obtain formula (I) or formula (II) product;
Wherein, X=R
1or R
4, Y=R
2or R
5
Or to take adjacent bromoacetophenone or a bromoacetophenone be raw material, under palladium catalyst, alkaline solution, solvent exist with R
2or R
5the boric acid microwave heating reaction replaced, obtain intermediate product B, and described intermediate product B is in potassium hydroxide-ethanol solution and by R
1or R
4the formaldehyde reaction replaced, obtain formula (I) or formula (II) product.
Wherein, X=R
1or R
4, Y=R
2or R
5
It is that raw material is prepared that the present invention also can select adjacent ethyl ketone base phenylo boric acid or an ethyl ketone base phenylo boric acid, is also to comprise the formation of cinnamophenone structure and replace aromatic ring introducing two portions, specifically comprises the steps:
Take adjacent ethyl ketone base phenylo boric acid or an ethyl ketone base phenylo boric acid is raw material, in potassium hydroxide-ethanol solution with by R
1or R
4the formaldehyde reaction replaced, obtain intermediate product C, described intermediate product C under palladium catalyst, alkaline solution, solvent exist with R
2or R
5the boric acid microwave heating reaction replaced, obtain formula (I) or formula (II) product;
Wherein, X=R
1or R
4, Y=R
2or R
5
Or to take adjacent ethyl ketone base phenylo boric acid or an ethyl ketone base phenylo boric acid be raw material, under palladium catalyst, alkaline solution, solvent exist with R
2or R
5the bromide microwave heating reaction replaced, obtain intermediate product B, and described intermediate product B is in potassium hydroxide-ethanol solution and by R
1or R
4the formaldehyde reaction replaced, obtain formula (I) or formula (II) product.
Wherein, X=R
1or R
4, Y=R
2or R
5
As a kind of most preferably scheme, described palladium catalyst most preferably is PdCl
2(dppf), described alkaline solution most preferably is solution of potassium carbonate, and described solvent most preferably is dioxane, and described microwave heating temperature is 150 ℃, and described microwave heating time is 15min.
R when formula (I) or formula (II) compound
3while being not hydrogen, can be with containing corresponding R
3the adjacent ethyl ketone base phenylo boric acid, an ethyl ketone base phenylo boric acid, adjacent bromine ethyl ketone or the bromoacetophenone that replace make formula (I) or formula (II) compound according to above-mentioned preparation method.
Described aryl replaces the application of chalcone compounds in preparing antitumor drug.
As a kind of most preferably scheme, described aryl replaces chalcone compounds in the anti-lung cancer of preparation, nasopharyngeal carcinoma, colorectal carcinoma, mammary cancer, the application in liver-cancer medicine.
By experiment, we find, fragrance replacement cinnamophenone of the present invention, and to A549, CNE2, SW480, MCF7, the cells such as HepG2 have restraining effect preferably, with the cinnamophenone that does not have aromatic base to replace, compare, and its activity obviously improves.
Compared with prior art, the present invention has following beneficial effect:
Aromatic base of the present invention replaces chalcone compounds, introduced aromatic base on its phenyl skeleton, form a class dibenzyl structure, figure space conformation that molecule presents a kind of " V ", with the chalcone compounds of existing non-dibenzyl structure, compare, cancer cells is had to higher inhibition activity, can be applicable to prepare antitumor drug.
Embodiment
Further explain the present invention below in conjunction with specific embodiment, but embodiment does not do any type of restriction to the present invention.Following eq refers to molar equivalent.
Embodiment 1 (E)-3-(4-p-methoxy-phenyl)-1-(3 '-fluoro-[1,1 '-xenyl]-3-yl) third-2-alkene-1-ketone (compound 1) is synthetic:
The 3-fluorobenzoic boric acid of bromoacetophenone and 5.2eq dioxane and 2M K between 4eq
2cO
31: 1 mixing solutions of the aqueous solution is made solvent, adds 0.2eq PdCl
2(dppf), 150 ℃ of microwave heating 15 minutes, ethyl acetate extraction organic layer, column chromatography for separation obtains intermediate 1-(3 '-fluoro-[1,1 '-xenyl]-the 3-yl) ethyl ketone, the 4-methoxybenzaldehyde dissolve with ethanol of 1eq intermediate and 1eq, add the KOH of 3eq to make catalyzer, stirring at room 20h, 1N HCl adjusts pH to 3, the ethyl acetate extraction, and organic layer uses column chromatography and obtains product (E)-3-(4-p-methoxy-phenyl)-1-(3 '-fluoro-[1,1 '-xenyl]-the 3-yl) third-2-alkene-1-ketone, productive rate 65%.
Product NMR analyzes:
1H NMR(500MHz，CDCl
3)δ8.19(t，J＝1.7Hz，1H)，8.00(ddd，J＝7.7，1.7，1.1Hz，1H)，7.83(d，J＝15.6Hz，1H)，7.77(ddd，J＝7.7，1.9，1.1Hz，1H)，7.63(dd，J＝9.1，2.4Hz，2H)，7.58(t，J＝7.7Hz，1H)，7.44(d，J＝15.6Hz，1H)，7.47-7.42(m，2H)，7.35(ddd，J＝10.1，2.7，1.3Hz，1H)，7.11-7.06(m，1H)，6.95(dd，J＝9.1，2.4Hz，2H)，3.86(s，3H).
13C NMR(100MHz，CDCl
3)δ190.38，164.53，162.09，161.90，145.17，142.71，142.63，140.52，139.28，131.19，130.56，130.45，129.24，127.88，127.62，127.14，123.01，122.99，119.71，114.77，114.56，114.36，114.14，55.52.
Embodiment 2 (E)-3-(4-p-methoxy-phenyl)-1-(4 '-fluoro-[1,1 '-xenyl]-2-yl) third-2-alkene-1-ketone (compound 3) is synthetic:
The 4-methoxybenzaldehyde dissolve with ethanol of the adjacent bromoacetophenone of 4eq and 4eq, add the KOH of 12eq to make catalyzer, stirring at room 20h, 1N HCl adjusts PH to 3, the ethyl acetate extraction, organic layer uses column chromatography and obtains intermediate (E)-3-(4-p-methoxy-phenyl)-1-(2-bromophenyl) third-2-alkene-1-ketone, dioxane and 2M K for the 4-fluorobenzoic boric acid of 1eq intermediate and 1.3eq
2cO
31: 1 mixing solutions of the aqueous solution is made solvent, adds 0.05eq PdCl
2(dppf), 150 ℃ of microwave heating 15 minutes, ethyl acetate extraction organic layer, column chromatography for separation obtains product (E)-3-(4-p-methoxy-phenyl)-1-(4 '-fluoro-[1,1 '-xenyl]-2-yl) third-2-alkene-1-ketone, productive rate 76%.
Product NMR analyzes:
1H NMR(500MHz，CDCl
3)δ7.61(dd，J＝7.6，1.4Hz，1H)，7.54(td，J＝7.5，1.4Hz，1H)，7.46(td，J＝7.5，1.2Hz，1H)，7.43(dd，J＝7.6，1.2Hz，1H)，7.36-7.32(m，2H)，7.31(d，J＝15.9Hz，1H)，7.26-7.23(m，2H)，7.07-7.02(m，2H)，6.85-6.81(m，2H)，6.49(d，J＝15.9Hz，1H)，3.81(s，3H).
13C NMR(100MHz，CDCl
3)δ196.30，163.69，161.68，161.23，144.35，140.00，139.68，136.64，136.61，130.74，130.66，130.50，130.15，129.96，128.68，127.45，127.17，124.62，115.53，115.32，114.34，55.28.
Embodiment 3 (E)-3-(4-p-methoxy-phenyl)-1-(3 '-fluoro-[1,1 '-xenyl]-2-yl) third-2-alkene-1-ketone (compound 11) is synthetic:
4.8eq dioxane and 2M K for the 3-bromofluoro benzene of adjacent bromobenzene boric acid and 4eq
2cO
31: 1 mixing solutions of the aqueous solution is made solvent, adds 0.2eq PdCl
2(dppf), 150 ℃ of microwave heating 15 minutes, ethyl acetate extraction organic layer, column chromatography for separation obtains intermediate 1-(3 '-fluoro-[1,1 '-xenyl]-the 2-yl) ethyl ketone, the 4-methoxybenzaldehyde dissolve with ethanol of 1eq intermediate and 1eq, add the KOH of 3eq to make catalyzer, stirring at room 20h, 1N HCl adjusts pH to 3, the ethyl acetate extraction, and organic layer uses column chromatography and obtains product (E)-3-(4-p-methoxy-phenyl)-1-(3 '-fluoro-[1,1 '-xenyl]-the 2-yl) third-2-alkene-1-ketone, productive rate 72%.
Product NMR analyzes:
1H NMR(400MHz，CDCl
3)δ8.17(t，J＝1.7Hz，1H)，8.01-7.94(m，1H)，7.83(d，J＝15.6Hz，1H)，7.77-7.72(m，1H)，7.64-7.54(m，5H)，7.44(d，J＝15.6Hz，1H)，7.20-7.14(m，2H)，6.98-6.92(m，2H)，3.87(s，3H).
13C NMR(100MHz，CDCl
3)δ190.43，163.96，161.84，161.51，145.06，140.67，139.10，136.40，131.02，130.37，129.07，128.88，128.80，127.55，127.26，126.90，119.66，115.89，115.70，114.48，55.37.
Embodiment 4 (E)-3-(3-hydroxyl-4-p-methoxy-phenyl)-1-(4 '-fluoro-[1,1 '-xenyl]-the 2-yl) third-2-alkene-1-ketone (compound 8)
The preparation method of reference example 1, difference is to replace 4-methoxybenzaldehyde with 3-hydroxyl-4-methoxybenzaldehyde, and the productive rate of compound 8 is 75%.
Product NMR analyzes:
1H NMR(400MHz，CDCl
3)δ7.60(dd，J＝7.6，1.3Hz，1H)，7.54(td，J＝7.5，1.4Hz，1H)，7.46(dd，J＝7.5，1.2Hz，1H)，7.42(d，J＝7.5Hz，1H)，7.36-7.30(m，2H)，7.26(d，J＝15.9Hz，1H)，7.08-7.01(m，2H)，6.88(d，J＝2.0Hz，1H)，6.84(dd，J＝8.3，2.0Hz，1H)，6.77(d，J＝8.3Hz，1H)，6.46(d，J＝15.9Hz，1H)，5.64(s，1H)，3.89(s，3H).
13C NMR(101MHz，CDCl
3)δ196.58，163.68，161.22，149.08，145.92，144.78，139.91，139.69，136.58，136.54，130.72，130.64，130.54，130.15，128.65，127.99，127.44，125.00，122.15，115.54，115.33，113.29，110.64，55.90.
Embodiment 5 (E)-3-(4-p-methoxy-phenyl)-1-(2-(6-fluorine pyridine 3-yl) phenyl) third-2-alkene-1-ketone (compound 9)
The preparation method of reference example 2, difference is, with the fluoro-4 pyridine boric acid of 6-, replaces the 4-fluorobenzoic boric acid, the productive rate of compound 9 is 82%.
Product NMR analyzes:
1H NMR(400MHz，CDCl
3)δ8.23(d，J＝2.5Hz，1H)，7.76(ddd，J＝8.4，7.7，2.6Hz，1H)，7.64(dd，J＝7.5，1.2Hz，1H)，7.58(td，J＝7.5，1.5Hz，1H)，7.52(td，J＝7.5，1.3Hz，1H)，7.42(dd，J＝7.6，0.9Hz，1H)，7.37-7.31(m，2H)，7.34(d，J＝16.0Hz，1H)，6.90(dd，J＝8.4，3.0Hz，1H)，6.88-6.83(m，2H)，6.64(d，J＝16.0Hz，1H)，3.83(s，3H).
13C NMR(101MHz，CDCl
3)δ195.09，163.90，161.71，161.52，146.86，146.71，145.48，141.45，141.37，139.71，135.63，134.13，134.09，130.45，130.22，129.91，128.49，127.93，126.60，124.03，114.21，108.90，108.53，55.04.
Embodiment 6 (E)-3-(3,4-Dimethoxyphenyl)-1-(3 '-fluoro-[1,1 '-xenyl]-the 2-yl) third-2-alkene-1-ketone (compound 12)
The preparation method of reference example 3, difference is, with Veratraldehyde, substitutes 4-methoxybenzaldehyde, the productive rate of compound 12 is 79%.
Product NMR analyzes:
1H NMR(400MHz，CDCl
3)δ7.65(dd，J＝7.6，1.3Hz，1H)，7.56(td，J＝7.5，1.4Hz，1H)，7.49(dd，J＝7.5，1.2Hz，1H)，7.47-7.43(m，1H)，7.34-7.27(m，1H)，7.31(d，J＝15.9Hz，1H)，7.16-7.11(m，2H)，6.99(ddd，J＝8.1，2.9，1.5Hz，1H)，6.91(dd，J＝8.3，1.9Hz，1H)，6.79(d，J＝8.3Hz，1H)，6.75(d，J＝1.9Hz，1H)，6.48(d，J＝15.9Hz，1H)，3.88(s，3H)，3.83(s，3H).
13C NMR(101MHz，CDCl
3)δ194.82，163.43，160.97，151.09，148.79，143.80，142.61，142.53，139.52，139.08，139.06，130.18，129.64，129.61，129.53，128.39，127.41，127.05，124.78，124.75，124.27，122.81，115.57，115.35，114.06，113.86，110.70，109.14，55.32，55.22.
Preparation method with reference to above-described embodiment has prepared compound 1～12.
Embodiment 7
This embodiment is the activity experiment data that the embodiment of the present application 1～6 prepares the compound 1～12 of gained.Provide the chalcones derivative of 13,14 two non-dibenzyl structures of compound to compare simultaneously.
The Cytostatic to tumor cell experiment:
Choose tumour cell A549 cell (human lung adenocarcinoma cell), CNE2 cell (KB cell), SW480 cell (human colon adenocarcinoma cell), MCF7 cell (human breast cancer cell), HepG2 cell (human liver cancer cell), with RPMI 1640 substratum containing 10% foetal calf serum, in 37 degrees centigrade, 5%CO
2, in cell culture incubator, hatch, after growing to 70%-80%, cell density goes down to posterity, for subsequent experimental.
Utilize the SRB staining, assessing compound suppresses the propagation of tumour cell.Tumour cell is planted 5000/100 μ l/ holes with RMPI 1640 substratum containing 5% foetal calf serum on 96 orifice plates, after 20 hours, compound is dissolved with DMSO, with 100 times of the RMPI 1640 substratum dilutions containing 5% foetal calf serum, every hole adds 100 μ l compounds, final concentration is 50.00 μ M, 16.67 μ M, 5.55 μ M, 1.85 μ M, 0.62 μ M, 0.21 μ M, 0.07 μ M, 0.02 μ M, then in 37 degrees centigrade, 5%CO
2, in cell culture incubator, hatch, with the negative contrast of DMSO, with acellular hole as a setting.After 48 hours, take out culture plate, every hole adds the trichoroacetic acid(TCA) 50 μ L fixed cells of 50% (mass/volume).In 4 ℃ of fixing 1h.After fixing the end, ultrapure water washing 5 times for each hole of culture plate, dry in 60 degrees centigrade of baking ovens.Take out the culture plate of drying, every hole adds 0.4% SRB dyestuff 100 μ L, and the 30min that dyes under room temperature, with 1% acetum washing 5 times, is dried in 60 degrees centigrade of baking ovens.Take out the culture plate of drying, add the Tris solution 150 μ L of pH=10.5 (10mM), concussion 10min.Measure the OD of 515nm place value on microplate reader.Medicine is expressed as the extracorporeal inhibiting rate of tumour cell:
Each hole inhibiting rate=[1-(this hole OD value-average OD value in blank hole)/(the average OD value of negative control hole-average OD value in blank hole)] * 100%
Take the concentration logarithmic value as X-coordinate, and inhibiting rate is that the ordinate zou matching suppresses curve, calculates IC
50.
Experimental result is as follows:
Experimental result and evaluation:
Compound 1～12 all has better restraining effect to 5 kinds of tumour cells, with the chalcone compounds 13,14 replaced without the connection aromatic group, compares, and activity obviously improves.
The above is the preferred embodiment of the present invention; it should be pointed out that the number for those skilled in the art, under the premise without departing from the principles of the invention; can also make some improvements and modifications, these improvements and modifications also are considered as protection domain of the present invention.
Claims (10)
1. aryl replaces chalcone compounds, it is characterized in that having structure as shown in formula I or formula II:
（Ⅰ） （Ⅱ）
Wherein, R
1, R
2, R
4, R
5for the aromatic series group or containing substituent aromatic series group, described aromatic series group is phenyl, furyl, pyridyl, pyrimidyl or pyrryl, described substituting group is hydroxyl, methoxyl group, oxyethyl group, methyl, ethyl, trifluoromethyl, any one or a few in halogen; R
3be selected from hydrogen, amino or-NHCOCH
3.
2. aryl replaces chalcone compounds as claimed in claim 1, it is characterized in that, described halogen is fluorine, chlorine or bromine.
3. aryl replaces chalcone compounds as claimed in claim 2, it is characterized in that, and in formula I, described R
4for the phenyl ring that bromine, chlorine, methoxyl group and/or hydroxyl replace, described R
5phenyl ring for the fluorine replacement.
4. aryl replaces chalcone compounds as claimed in claim 2, it is characterized in that, and in formula II, described R
1for furan nucleus or the phenyl ring that replaced by fluorine, bromine, methoxyl group and/or hydroxyl, described R
2phenyl ring or pyridine ring for fluorine or methoxy substitution.
5. aryl replaces chalcone compounds as claimed in claim 1, it is characterized in that, and in formula II, described R
1during for furan nucleus, the hydrogen atom of furan nucleus can also be replaced by alkyl.
6. state aryl as claim 5 and replace chalcone compounds, it is characterized in that, described alkyl is methyl.
7. the described aryl of claim 1 replaces the preparation method of chalcone compounds, it is characterized in that, comprises the steps:
With R
3the adjacent bromoacetophenone or the bromoacetophenone that replace are raw material, in potassium hydroxide-ethanol solution and by R
1or R
4the formaldehyde reaction replaced, obtain intermediate product A, described intermediate product A under palladium catalyst, alkaline solution, solvent exist with R
2or R
5the boric acid microwave heating reaction replaced, obtain formula I or formula II product;
Or to take adjacent bromoacetophenone or a bromoacetophenone be raw material, under palladium catalyst, alkaline solution, solvent exist with R
2or R
5the boric acid microwave heating reaction replaced, obtain intermediate product B, and described intermediate product B is in potassium hydroxide-ethanol solution and by R
1or R
4the formaldehyde reaction replaced, obtain formula I or formula II product.
8. preparation method claimed in claim 1, is characterized in that, with R
3the adjacent ethyl ketone base phenylo boric acid or the ethyl ketone base phenylo boric acid that replace are raw material, in potassium hydroxide-ethanol solution and by R
1or R
4the formaldehyde reaction replaced, obtain intermediate product C, described intermediate product C under palladium catalyst, alkaline solution, solvent exist with R
2or R
5the bromine microwave heating reaction replaced, obtain formula I or formula II product;
Or to take adjacent ethyl ketone base phenylo boric acid or an ethyl ketone base phenylo boric acid be raw material, under palladium catalyst, alkaline solution, solvent exist with R
2or R
5the bromine microwave heating reaction replaced, obtain intermediate product B, and described intermediate product B is in potassium hydroxide-ethanol solution and by R
1or R
4the formaldehyde reaction replaced, obtain formula I or formula II product.
9. preparation method as claimed in claim 7 or 8, is characterized in that, described palladium catalyst is PdCl
2(dppf), described alkaline solution is solution of potassium carbonate, and described solvent is dioxane; Described microwave heating temperature is 150 ℃, and described microwave heating time is 15min.
10. the described aryl of claim 1 replaces the application of chalcone compounds in preparing antitumor drug.
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| CN103102331B (en) * | 2013-01-17 | 2015-05-27 | 浙江大学 | Pharmaceutical application of chalcone compound containing piperazine ring |
| CN103833540B (en) * | 2013-11-29 | 2016-06-08 | 中山大学 | A kind of beta substitution cinnamophenone analogue and its preparation method and the application in preparation NSC 630176 |
| CN103755732B (en) * | 2014-01-23 | 2016-06-08 | 中山大学 | Adjacent phenyl chalcone compounds and its preparation method and application |
| CN103880623A (en) * | 2014-02-28 | 2014-06-25 | 天津科技大学 | 4,2',4'-triethoxy-5' substituted chalcone derivatives and preparation method and application thereof |
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| CN105295893B (en) * | 2014-07-23 | 2017-08-04 | 中山大学 | A kind of application of adjacent phenyl chalcone compounds in fluorescence probe |
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