CN104592182A - Caffeic acid phenethyl ester compounds and preparation method and application thereof - Google Patents
Caffeic acid phenethyl ester compounds and preparation method and application thereof Download PDFInfo
- Publication number
- CN104592182A CN104592182A CN201410856290.XA CN201410856290A CN104592182A CN 104592182 A CN104592182 A CN 104592182A CN 201410856290 A CN201410856290 A CN 201410856290A CN 104592182 A CN104592182 A CN 104592182A
- Authority
- CN
- China
- Prior art keywords
- compound
- cancer cell
- phenethyl ester
- formula
- caffeic acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/34—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D309/36—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with oxygen atoms directly attached to ring carbon atoms
- C07D309/38—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with oxygen atoms directly attached to ring carbon atoms one oxygen atom in position 2 or 4, e.g. pyrones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Abstract
The invention discloses caffeic acid phenethyl ester compounds. The compounds have a structure shown in the chemical general formula A or B, wherein R1 in the formula A is substituent group on one or more benzene ring; R1 is independently selected from H, alkyl, alkoxy, halogen, nitryl, phenyl or trimethyl halide; R2 in the formula B is independently selected from the following groups shown in the specification. The compounds disclosed by the invention have better inhibiting function for the proliferation of a plurality of human tumor cells, and the compounds can be used for preparing anti-tumor drugs; therefore, the compounds have very high medical value and wide market prospect. (The formulae A and B are shown in the specification).
Description
Technical field
The invention belongs to medical art, be specifically related to a kind of caffeic acid phenethyl ester compound and preparation method thereof and application.
Background technology
Along with the change of human habitat, standard of living and mode of life and the progress of medical science, general transmissible disease is controlled gradually, and the cancers such as malignant tumour then become day by day common and one of principal disease of serious threat human life and quality of life.End 2013, the human death caused by cancer accounts for 23% of all disease deaths, becomes the second-biggest-in-the-world height morbidity and high mortality disease that are only second to cardiovascular disorder.In the middle of cancer, lung cancer is modal a kind of cancer causing death, accounts for all number of cancer deaths' 1/4th.Other, all easily cause death as more common mammary cancer in the more common prostate cancer in man and women.Mention cancer cells, just have to carry tumour cell.Tumour is that other tissue growths of a part of cell of health and body are inharmonious, shows as at random, multiple fission without limit, and increasing into a large tissue block is then tumour.Tumour have optimum also have pernicious.Be only compressing surrounding tissue when innocent tumour increases gradually, and malignant tumour can also infiltrate towards periphery except compressing, namely tumor tissues constantly invades surrounding tissue, and this malignant tumour is just called " cancer ".The disease stoping the growth of tumour cell can reduce cancer sends out rate, therefore the research of antitumor drug is significant for a solution human cancer disease difficult problem, finding effective antitumour medicine and method, thoroughly capture cancer, is the important research topic of world medical circle.
CAPE (CAPE) is one of main component in propolis, has the multiple efficacies such as antitumor, all has broad application prospects in food, medical science and other field.Many derivatives that is natural or synthetic also have and pharmacological action like Caffeic acids, therefore, synthesize new caffeic acid phenethyl ester compound and wait the research of medicine significant for antitumor.
Summary of the invention
For the deficiencies in the prior art, the invention provides a kind of caffeic acid phenethyl ester compound.
Another object of the present invention is to provide caffeic acid phenethyl ester compound and is preparing the application in antitumor drug.
Another object of the present invention is to provide a class caffeic acid phenethyl ester compound and is preparing the application in anti-cervical cancer cell, cancer cell of oral cavity, breast cancer cell, lung adenocarcinoma cell and neuroglial cytoma medicine.
Another object of the present invention is to provide the preparation method of caffeic acid phenethyl ester compound.
Above-mentioned purpose of the present invention is achieved by the following technical programs.
A kind of caffeic acid phenethyl ester compound, has structure shown in chemical general formula A or B:
Wherein, R in A formula
1for the substituting group on one or more phenyl ring, described R1 is selected from alone H, alkyl, alkoxyl group, halogen, nitro, phenyl or trihalogenmethyl; R in B formula
2be selected from alone
The present invention simulates the structure of CAPE, design and synthesize the caffeic acid phenethyl ester compound that a class is new, and find that the propagation of compound to multiple human tumor cell of synthesis is inhibited, drug concentration required when being applied to antitumor by them, far below concentration when adopting CAPE (CAPE) antitumor, illustrates that compound of the present invention has the effect of efficient inhibition tumor cell.
Preferably, described caffeic acid phenethyl ester compound has structure shown in chemical general formula A, R in A formula
1for one or more benzene ring substituents, described R1 is selected from alone alkyl, alkoxyl group, halogen or trihalogenmethyl.The propagation of described compound to cervical cancer cell, cancer cell of oral cavity, breast cancer cell, lung adenocarcinoma cell, glioblastoma cells or neuroglial cytoma has certain restraining effect.
Preferably, described caffeic acid phenethyl ester compound has structure shown in chemical general formula A, R in A formula
1for one or more benzene ring substituents, described R1 is selected from alone halogen or alkyl.Described compound all has efficient restraining effect to the propagation of cervical cancer cell, cancer cell of oral cavity, breast cancer cell, lung adenocarcinoma cell and neuroglial cytoma.
The present invention also provides described caffeic acid phenethyl ester compound preparing the application in antitumor drug.The present invention finds, the propagation of described caffeic acid phenethyl ester compound to one or more tumour cells is inhibited, therefore can be used for preparing in corresponding antitumor drug.
Preferably, described antitumor drug refers to one or more in anti-cervical cancer cell, cancer cell of oral cavity, breast cancer cell, lung adenocarcinoma cell, glioblastoma cells or neuroglial cytoma medicine.
The present invention also provides a compounds preparing the application in anti-cervical cancer cell, cancer cell of oral cavity, breast cancer cell, lung adenocarcinoma cell and neuroglial cytoma medicine, and described compound has structure shown in chemical general formula A, and R in A formula
1for one or more benzene ring substituents, described R1 is selected from alone halogen or alkyl.Experiment finds, this compounds all has good restraining effect to above-mentioned five kinds of tumour cells, adopts the above-claimed cpd of lower concentration dosage effectively can suppress the propagation of above-mentioned various cancer cells.
A kind of preparation method of caffeic acid phenethyl ester compound, comprise the steps: with 4-hydroxyl-6-methyl 2H-pyrone as raw material, through methyl-sulfate, 4-methoxyl group-6-methyl 2H-pyrone is obtained to methylating of hydroxyl, then by tin anhydride, 6-methyl oxidation is obtained 4-methoxyl group-6-aldehyde radical 2H-pyrone, again reaction product and propanedioic acid are obtained 4-methoxyl group-2H-pyrone-6-vinylformic acid at 100 DEG C by Knoevenagel condensation reaction, carry out esterification again with phenylethyl alcohol or heterocycle alcohol compound and obtain pyrans keto-acid CAPE compounds.
The present invention synthesizes caffeic acid phenethyl ester compound with 4-methoxyl group-6-methyl 2H-pyrone for raw material, and raw material is cheap and easy to get, and synthetic method is simple to operation, product stable, and productive rate is high.
Compared with prior art, beneficial effect of the present invention is: compound of the present invention is all inhibited to the propagation of multiple human tumor cell, drug concentration required when being applied to antitumor by them is far below concentration when adopting CAPE (CAPE) antitumor, illustrate that compound of the present invention has the effect of efficient inhibition tumor cell, can antitumor drug be prepared into, there are very high medical value and wide market outlook.
Figure of description
Fig. 1 is the drug level of 5o compound and the curve relation figure of MCF-7 cancer cell multiplication inhibiting rate.
Fig. 2 is the drug level of 5o compound and the curve relation figure of C6 cancer cell multiplication inhibiting rate.
Fig. 3 is the drug level of 5o compound and the curve relation figure of HSC-2 cancer cell multiplication inhibiting rate.
Fig. 4 is the drug level of 5o compound and the curve relation figure of Hela cancer cell multiplication inhibiting rate.
Fig. 5 is the drug level of 5o compound and the curve relation figure of A549 cancer cell multiplication inhibiting rate.
Embodiment
Below in conjunction with Figure of description and specific embodiment, the present invention is described in further details, but embodiment does not limit in any form the present invention.Unless stated otherwise, the present invention adopts reagent, method and apparatus are the art conventional reagent, method and apparatus.
The preparation of embodiment 1 4-methoxyl group-6-methyl 2H-pyrone (compound 2)
By 62.4g K
2cO
3with 9.8mL Me
2sO
4join 200mL anhydrous propanone is housed flask inside, then repeatedly add 10g 4-hydroxyl-6-methyl 2H-pyrone (being numbered compound 1), stirred overnight at room temperature in batches.Filter, solids washed with acetone, filtrate is through underpressure distillation, and the crude by column chromatography obtained obtains white solid 9.3g, and white solid is 4-methoxyl group-6-methyl 2H-pyrone (being numbered compound 2), and productive rate is 84%.
The preparation of embodiment 2 4-methoxyl group-6-aldehyde radical 2H-pyrone (compound 3)
Under nitrogen protection, by 5.6g 4-methoxyl group-6-methyl 2H-pyrone (compound 2) and 22g SeO
2be dissolved in 150mL dioxan is housed sealed tube inside, at the temperature of 160 DEG C react 5 hours.After reaction terminates, be cooled to room temperature, filter, solid with methylene chloride washs, and crude by column chromatography obtains solid 5.6g, and solid product is 4-methoxyl group-6-aldehyde radical 2H-pyrone (being numbered compound 3), and productive rate is 91%.
The preparation of embodiment 3 4-methoxyl group-2H-pyrone-6-vinylformic acid (compound 4)
Be dissolved in 10mL pyridine with 2.08g propanedioic acid by 3.08g 4-methoxyl group-6-aldehyde radical 2H-pyrone (compound 3), add 0.1mL piperidines, reaction solution is heated to 110 DEG C, reacts 5 hours.After reaction terminates, reaction solution is poured in the hydrochloric acid soln of 2M, cool to room temperature.Filter, filter residue washes with water.Crude by column chromatography purifying, obtains solid 1.84g, and solid product is 4-methoxyl group-2H-pyrone-6-vinylformic acid (being numbered compound 4), and productive rate is 47%.
The preparation of embodiment 4 caffeic acid phenethyl ester compound (compound 5a ~ u)
0.588g 4-methoxyl group-2H-pyrone-6-vinylformic acid (compound 4) is dissolved in 30mL methylene dichloride, add EDCHCl (1.2eq., 1.25g), DMAP (0.1eq., 0.8g), and phenylethyl alcohol or heterocycle alcohol compound (1.2eq.), reaction solution stirring at room temperature 24h.After reaction terminates, add the saturated common salt aqueous solution, use dichloromethane extraction.Crude by column chromatography purifying, the solid product obtained is various caffeic acid phenethyl ester compounds, and the synthetic route of described caffeic acid phenethyl ester compound is:
Prepared multiple caffeic acid phenethyl ester compound by said synthesis route, wherein will be numbered compound 5a ~ u respectively by portion of product, its productive rate and H spectrum analysis are in table 1.
Table 1 caffeic acid phenethyl ester compound is analyzed
Note: in table structure division curve before represent identical structure, represent concrete the position of substitution on phenyl ring of R1 and substituted radical after curve, or represent the concrete structure of R2.Following table is same.
The mensuration of embodiment 5 compound 5a ~ u anti-tumor activity
(1) cell cultures
Vitro culture Hela (clone of cervical cancer cell), HSC-2 (human oral cancer cell), MCF-7 (breast cancer cell), A549 (human lung adenocarcinoma cell), C6 (mouse neuroglial cytoma).Use containing 10% foetal calf serum, the DMEM high glucose medium of 1% dual anti-(penicillin, Streptomycin sulphate), 37 DEG C, conventional maintain carried out to above-mentioned cell under 5% gas concentration lwevel condition and go down to posterity.
(2) testing method
In 96 orifice plates, Hela, HSC-2, MCF-7 and A549 cell is 3500/hole, C6 cell 5000/hole, substratum 100 μ L/ hole, cultivates 24h.Configuration drug concentration gradient is 50 μMs, 25 μMs, 12.5 μMs, 6.25 μMs, 1 μM, 0.5 μM.The multiple hole of each concentration three, ensures that the content of DMSO in substratum is no more than 1%.The perfect medium group arranging 10% is blank group, and the normal cell group not adding medicine is control group (con).After 48h, every hole adds 20 μ L MTT solution (2.5mg/mL, with the preparation of sterilizing ultrapure water).Continue to hatch 4h, stop cultivating, careful suction abandons culture supernatant in hole, and every hole adds 120 μ L DMSO, shaking table vibration 20min.Microplate reader is utilized to measure the optical density(OD) OD value at 492nm place, to reflect number of viable cells.
(3) data processing
Inhibiting rate=100 × (OD-OD
blank)/(OD
con-OD
blank).Take inhibiting rate as ordinate zou, the denary logarithm value (lg) of drug level is X-coordinate, obtains dose-effect curve, and Fig. 1 ~ 5 result shows the drug level of compound 5o that adopts aforesaid method to measure and various cancer cells and to rise in value inhibiting rate graphic representation.Result shows, and along with the increase of 5o drug level, all effectively can suppress the propagation of MCF-7, C6, HSC-2, Hela, A549 cell, and 5o is for the IC of above-mentioned tumour cell
50(IC
50concentration for medicine when inhibiting rate is 50%) be respectively 2.61 μMs, 3.45 μMs, 1.19 μMs, 0.50 μM, 1.15 μMs, illustrate that the 5o of lower concentration dosage effectively can suppress the propagation of above-mentioned various cancer cells.
(4) analyze the activity of the anti-5 kinds of human tumor cells of the caffeic acid phenethyl ester compound (compound 5a ~ u) prepared, the results are shown in Table 2.Result shows, for these five kinds of human tumor cells of MCF-7, C6, HSC-2, Hela, A549, and the IC of CAPE (CAPE)
50be respectively 85.21 μMs, 12.61 μMs, 28.35 μMs, 68.04 μMs, 82.91 μMs, and prepare caffeic acid phenethyl ester compound 5b, 5e, 5o, 5t to these five kinds of tumour cells and also all have restraining effect, and its IC
50lower than the IC of CAPE (CAPE)
50, illustrate that drug concentration required when being applied to antitumor by them will lower than concentration when adopting CAPE (CAPE) antitumor, they have the effect of efficient inhibition tumor cell.In addition, prepare multiple also inhibited in these five kinds of tumour cells of caffeic acid phenethyl ester compound 5g, 5n, 5p, 5q, 5s, and its IC
50lower than the IC of the CAPE (CAPE) when being applied to corresponding tumour cell
50, drug concentration required when the tumour they being applied to anti-particular types is described will lower than concentration when adopting CAPE (CAPE), and they have the efficient effect suppressed to some tumour cell.
The activity of table 2 caffeic acid phenethyl ester compound antitumor cell
Claims (7)
1. a caffeic acid phenethyl ester compound, is characterized in that, has structure shown in chemical general formula A or B:
Wherein, R in A formula
1for the substituting group on one or more phenyl ring, described R1 is selected from alone H, alkyl, alkoxyl group, halogen, nitro, phenyl or trihalogenmethyl; R in B formula
2be selected from alone
,
,
,
or
.
2. compound according to claim 1, is characterized in that, described caffeic acid phenethyl ester compound has structure shown in chemical general formula A, R in A formula
1for one or more benzene ring substituents, described R1 is selected from alone alkyl, alkoxyl group, halogen or trihalogenmethyl.
3. compound according to claim 1, is characterized in that, described caffeic acid phenethyl ester compound has structure shown in chemical general formula A, R in A formula
1for one or more benzene ring substituents, described R1 is selected from alone halogen or alkyl.
4. compound according to claim 1 is preparing the application in antitumor drug.
5. application according to claim 4, is characterized in that, described antitumor drug refer in anti-cervical cancer cell, cancer cell of oral cavity, breast cancer cell, lung adenocarcinoma cell, glioblastoma cells or neuroglial cytoma medicine one or more.
6. compound according to claim 3 is preparing the application in anti-cervical cancer cell, cancer cell of oral cavity, breast cancer cell, lung adenocarcinoma cell and neuroglial cytoma medicine.
7. the preparation method of compound described in claim 1, it is characterized in that, comprise the steps: with 4-hydroxyl-6-methyl 2H-pyrone as raw material, through methyl-sulfate, 4-methoxyl group-6-methyl 2H-pyrone is obtained to methylating of hydroxyl, then by tin anhydride, 6-methyl oxidation is obtained 4-methoxyl group-6-aldehyde radical 2H-pyrone, again reaction product and propanedioic acid are obtained 4-methoxyl group-2H-pyrone-6-vinylformic acid by condensation reaction, then carry out esterification with phenylethyl alcohol or heterocycle alcohol compound and obtain pyrans keto-acid CAPE compounds.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410856290.XA CN104592182B (en) | 2014-12-31 | 2014-12-31 | A kind of caffeic acid phenethyl ester type compound and preparation method and application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410856290.XA CN104592182B (en) | 2014-12-31 | 2014-12-31 | A kind of caffeic acid phenethyl ester type compound and preparation method and application |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104592182A true CN104592182A (en) | 2015-05-06 |
| CN104592182B CN104592182B (en) | 2017-01-04 |
Family
ID=53118286
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410856290.XA Expired - Fee Related CN104592182B (en) | 2014-12-31 | 2014-12-31 | A kind of caffeic acid phenethyl ester type compound and preparation method and application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104592182B (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108129443A (en) * | 2017-12-29 | 2018-06-08 | 山东省医学科学院药物研究所 | Caffeic acid ester analog derivative and preparation method thereof |
| CN114377001A (en) * | 2022-03-01 | 2022-04-22 | 贵州大学 | Application of caffeic acid phenethyl ester in preparation of anti-cervical cancer drugs |
| CN115737819A (en) * | 2022-09-28 | 2023-03-07 | 众爱数字医疗科技(广东)有限公司 | Pharmaceutical composition, preparation method and application thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104016862A (en) * | 2013-02-28 | 2014-09-03 | 北京大学 | Preparation and application of caffeic acid ethyl benzene phenol hydroxyl protecting derivative taken as neuroprotective agent and antitumor medicine |
-
2014
- 2014-12-31 CN CN201410856290.XA patent/CN104592182B/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104016862A (en) * | 2013-02-28 | 2014-09-03 | 北京大学 | Preparation and application of caffeic acid ethyl benzene phenol hydroxyl protecting derivative taken as neuroprotective agent and antitumor medicine |
Non-Patent Citations (4)
| Title |
|---|
| DAVID RÖNSBERG ET AL.: "Secondary metabolites from the endophytic fungus Pestalotiopsis virgatula isolated from the mangrove plant Sonneratia caseolaris", 《TETRAHEDRON LETTERS》 * |
| LUISA COOK ET AL.: "Inhibition of Human Sputum Elastase by Substituted 2-Pyrones", 《J. MED. CHEM.》 * |
| MOHAMMAD SHAWKAT ALI ET AL.: "Six New Diarylheptanoids from the Seeds of Alpinia blepharocalyx", 《J.NAT.PROD.》 * |
| SHOSUKE YAMAMURA ET AL.: "Reactions of 4-methoxy-2-oxopyran-6-ylacetic Acid With Acid Anhydrides", 《J. CHEM. SOC. (C)》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108129443A (en) * | 2017-12-29 | 2018-06-08 | 山东省医学科学院药物研究所 | Caffeic acid ester analog derivative and preparation method thereof |
| CN108129443B (en) * | 2017-12-29 | 2020-04-03 | 山东省医学科学院药物研究所 | Caffeic acid ester derivatives and preparation method thereof |
| CN114377001A (en) * | 2022-03-01 | 2022-04-22 | 贵州大学 | Application of caffeic acid phenethyl ester in preparation of anti-cervical cancer drugs |
| CN115737819A (en) * | 2022-09-28 | 2023-03-07 | 众爱数字医疗科技(广东)有限公司 | Pharmaceutical composition, preparation method and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104592182B (en) | 2017-01-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105793261B (en) | Pyrazolopyrimidine compound | |
| Wang et al. | The conversion of oridonin to spirolactone-type or enmein-type diterpenoid: Synthesis and biological evaluation of ent-6, 7-seco-oridonin derivatives as novel potential anticancer agents | |
| CN104592182A (en) | Caffeic acid phenethyl ester compounds and preparation method and application thereof | |
| US9029403B2 (en) | Treatment of ovarian cancer with benzylidenebenzohydrazides | |
| CN104086617A (en) | Cleistanone dimethylamine derivative and preparation method and use thereof | |
| CN103191095A (en) | STAT (Signal Transducer And Activator Of Transcription)3 signal channel small-molecule inhibitor and application thereof | |
| CN102924450A (en) | 6-(5-pyridyl)-1,2,4-triazolopyridine compound, and preparation method and application thereof | |
| CN103130632A (en) | 1-substituted benzylidene-2-naphthalenone derivative, preparation method thereof and use thereof | |
| CN101434524B (en) | 4-(4-hydroxy-3-methoxybenzene methylene) curcumin, preparation thereof and use in preparing anti-cancer medicament | |
| CA2855245A1 (en) | Treatment of ovarian cancer with 2-amino-4h-naphtho[1,2-b]pyran-3-carbonitriles | |
| CN106187985B (en) | Benzo coumarin kind compound with anti-breast cancer activity and preparation method thereof | |
| CN104003998A (en) | Oridonin 14-0-sustituted nitrogen mustard derivatives, and preparation method and application thereof | |
| CN104744518A (en) | Metallic ruthenium complex as well as preparation method and application thereof | |
| CN109734561A (en) | A kind of farnesyl phenolic compound and its pharmaceutical composition and its application | |
| CN103467258B (en) | A kind of Lignanoids compounds and its production and use | |
| CN103980174B (en) | Substituted pyrrolidin dithiocarbamic acid bismuth (III) title complex and preparation method thereof and preparing the application in antitumor drug | |
| CN101716175B (en) | New application of 3-amido-6-(4-methoxyphenyl) thiopheno[2, 3-b] pyridine-2-formamide | |
| CN103044363A (en) | Paclitaxel derivative as well as preparation method and application thereof | |
| CN103772317B (en) | 2-methoxyl group-3-replaces sulfonamido-5-(2-acetylaminohydroxyphenylarsonic acid 6-benzothiazolyl) benzamide compound and preparation method thereof and purposes | |
| CN103965049A (en) | Compound containing small tri-cyclic ring and preparation method thereof, and application of compound in preparation of antitumor drug | |
| CN102649750B (en) | Curcumin salicylic acid monoester and synthesis method thereof and application curcumin salicylic acid monoester in anti-tumor and anti-inflammatory aspects | |
| CN116621895A (en) | Flavonoid glycoside and application thereof in preparation of antitumor drugs | |
| CN105541696A (en) | Anti-tumor compound and preparation method and application thereof | |
| CN104910168A (en) | Daphmalenine A O-(diethylamino) ethyl derivative, preparation method and uses thereof | |
| CN104069103A (en) | Pharmaceutical composition for treating brain glioma under synergistic interaction |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20170808 Address after: 511458, Guangzhou, Guangdong province Nansha District City Ring Road, south 8, a self-made (production building) 408 Patentee after: Guangzhou city love new Pu Pharmaceutical Technology Co. Ltd. Address before: 510006 Panyu District City, Guangdong Province, University of outer ring road, No., No. 132 Patentee before: Sun Yat-sen University |
|
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20170104 Termination date: 20181231 |