CN105254699B - 4-(4 minute-trifluoromethyl) phenyl-2-dehydroepiandrosterone-17 minute-hydrazone thiazole as well as preparation method and application thereof - Google Patents
4-(4 minute-trifluoromethyl) phenyl-2-dehydroepiandrosterone-17 minute-hydrazone thiazole as well as preparation method and application thereof Download PDFInfo
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Abstract
The invention discloses 4-(4 minute -trifluoromethyl) phenyl-2-dehydroepiandrosterone-17 minute -hydrazone thiazole as well as a preparation method and application thereof, and the chemical formula of the 4-(4 minute -trifluoromethyl) phenyl-2-dehydroepiandrosterone-17 minute -hydrazone thiazole is shown in a figure below; the compound obtained through the preparation method has obviously inhibiting effect on various hepatoma cell lines such as liver cancer, lung cancer, gastric cancer, cervical cancer, prostate cancer and colon cancer, is low in toxicity, and is not liable to produce drug resistance; the invention also provides the preparation method and application of the compound, and the preparation method is simple and easy, and is in favor of market promotion and application.
Description
Technical field
The present invention relates to a kind of 4- (4 '-trifluoromethyl) phenyl -2- dehydroepiandros-sterones -17 '-hydrazone thiazole and preparation method thereof
And purposes.
Background technology
Cancer is a kind of principal disease for endangering human health, captures the problem that malignant tumour is modern medicine,
It is the maximum challenge of medical industry processed now.At present, various types of antineoplastic continuously emerges and clinically obtains
Must apply, but the antineoplastic for clinically using is larger due to the toxicity that it is caused to tissue, greatly limit
Their use scope.Therefore, the cancer therapy drug for finding efficient, high selectivity and Small side effects is the main of cancer therapy drug exploitation
Direction.
In antineoplastic, clinically it is used to treat the medicine Finasteride of hyperplasia of prostate at present, for treating
The medicine estramustine phosphate sodium (Estramustine phosphate sodium) of advanced prostate cancer, Abiraterone acetate
It is single with the medicine Exemestane for treating menopausal women breast cancer, and the conduct developed by EntreMed companies recently
Therapy is used for stabilization or recurrence Huppert's disease and the cancer therapy drug methoxyestradiol (commodity of prostate cancer therapy
Name：Panzem), they belong to steroidal antineoplastic.But there is complex structure in current steroidal antineoplastic, act on position
Point is more, causes for poor selectivity, and its mechanism of action, material base are without clear and definite theoretical explanation, therefore structural formula, targeting
It is respectively provided with not controllability.
The content of the invention
It is an object of the invention to solve at least the above, and provide the advantage that at least will be described later.
It is a still further object of the present invention to provide a kind of compound：4- (4 '-trifluoromethyl) phenyl -2- dehydroepiandros-sterones -
17 '-hydrazone thiazole, it has obvious to various tumor cell strains such as liver cancer, lung cancer, stomach cancer, cervical carcinoma, prostate cancer, colon cancers
Inhibitory action, and toxicity is low, is not likely to produce drug resistance, present invention also offers the preparation method and purposes of the compound,
The preparation method is simple and easy to apply, is conducive to marketing application.
In order to realize these purposes of the invention and further advantage, there is provided a kind of 4- (4 '-trifluoromethyl) phenyl-
2- dehydroepiandros-sterone -17 '-hydrazone thiazoles, it has below formula：
A kind of preparation method of described 4- (4 '-trifluoromethyl) phenyl -2- dehydroepiandros-sterone -17 '-hydrazone thiazoles, including
Following steps：
Step one, take respectively by weight 100~120 parts of dehydroepiandros-sterones, 35~45 parts of thiosemicarbazides and 100~
120 parts of bromo- 4 '-trifluoromethyl acetophenone mixing of 2-, and being added thereto to absolute ethyl alcohol is completely dissolved it, carries out microwave anti-
Should, reaction temperature is 80~90 DEG C, until reaction is completed, is cooled to room temperature, obtains the first intermediate product；
Step 2, by first intermediate product remove solvent, purification, in the material after purification add distilled water mix
Close, then be extracted with ethyl acetate 2~4 times, take organic phase, obtain the second intermediate product, wherein, the addition of distilled water is：Often
112mg dehydroepiandros-sterones add 25~35ml distilled water；
Step 3, second intermediate product is washed with saturated sodium bicarbonate solution, saturated nacl aqueous solution successively, gone forward side by side
The mixture that dried process is obtained further is removed solvent by row dried process to remove moisture, purification, and carries out column chromatography point
From obtaining pale yellowish oil liquid, i.e. 4- (4 '-trifluoromethyl) phenyl -2- dehydroepiandros-sterones -17 '-hydrazone thiazole.
Preferably, the preparation method of described 4- (4 '-trifluoromethyl) phenyl -2- dehydroepiandros-sterones -17 '-hydrazone thiazole,
Microwave power is 250~350W in the step one.
Preferably, the preparation method of described 4- (4 '-trifluoromethyl) phenyl -2- dehydroepiandros-sterones -17 '-hydrazone thiazole,
The method of the removal solvent in the step one and step 3 is vacuum distillation.
Preferably, the preparation method of described 4- (4 '-trifluoromethyl) phenyl -2- dehydroepiandros-sterones -17 '-hydrazone thiazole,
Dried process in the step 3 uses anhydrous sodium sulfate.
Preferably, the preparation method of described 4- (4 '-trifluoromethyl) phenyl -2- dehydroepiandros-sterones -17 '-hydrazone thiazole,
The method for checking reaction to complete in the step one：By the column chromatography chromatogram method tracking and monitoring of the mixture in reaction, until prison
Measure the dehydroepiandros-sterone in mixture and disappear and then stop reaction.
Preferably, the preparation method of described 4- (4 '-trifluoromethyl) phenyl -2- dehydroepiandros-sterones -17 '-hydrazone thiazole,
Column chromatography for separation in the step 4, eluant, eluent is VDichloromethane∶VEthyl acetate=50: 1.
A kind of purposes of described 4- (4 '-trifluoromethyl) phenyl -2- dehydroepiandros-sterones -17 '-hydrazone thiazole, its purposes exists
In, 4- (4 '-trifluoromethyl) phenyl -2- dehydroepiandros-sterones -17 '-hydrazone thiazole is used to prepare treating cancer medicine should
With.
Preferably, the purposes of described 4- (4 '-trifluoromethyl) phenyl -2- dehydroepiandros-sterones -17 '-hydrazone thiazole, wherein
Cancer includes：Liver cancer, lung cancer, stomach cancer, cervical carcinoma, prostate cancer and colon cancer.
The present invention at least includes following beneficial effect：A kind of compound is provided：4- (4 '-trifluoromethyl) phenyl -2- dehydrogenations
Epiandrosterone -17 '-hydrazone thiazole, it is selective high, various to liver cancer, lung cancer, stomach cancer, cervical carcinoma, prostate cancer, colon cancer etc. swollen
Tumor cell strain has obvious inhibitory action, and toxicity is low, is not likely to produce drug resistance, greatly reduces the cell toxicant for discharging
Injury of the plain medicine to human body, present invention also offers the preparation method and purposes of the compound, the preparation method is simple and easy to apply,
Be conducive to marketing application.
Further advantage of the invention, target and feature embody part by following explanation, and part will also be by this
The research and practice of invention and be understood by the person skilled in the art.
Specific embodiment
With reference to embodiment, the present invention is described in further detail, to make those skilled in the art with reference to specification
Word can be implemented according to this.
It should be appreciated that it is used herein such as " have ", "comprising" and " including " term do not allot one or many
The presence or addition of individual other elements or its combination.
<Embodiment 1>
A kind of 4- (4 '-trifluoromethyl) phenyl -2- dehydroepiandros-sterone -17 '-hydrazone thiazoles, it has below formula：
A kind of preparation method of described 4- (4 '-trifluoromethyl) phenyl -2- dehydroepiandros-sterone -17 '-hydrazone thiazoles, including
Following steps：
Step one, weighing 100~120mg of dehydroepiandros-sterone, the bromo- 4 '-trifluoromethylbenzene second of thiosemicarbazides 35~45mg, 2-
100~120mg of ketone is put into 100mL two-neck bottles, and is completely dissolved it to its addition 12~18mL absolute ethyl alcohol, adds magneton
After be placed in microwave synthesis reactor, insert temperature sensor, power is adjusted to 250~350W, preset temperature is 80~90
DEG C, TLC tracing detections stop reaction after raw material point disappears substantially.Room temperature is cooled to, the first intermediate product is obtained；
Step 2, the first intermediate product vacuum distillation is gone out most of solvent, adds the mixing of 25~35mL distilled water,
It is extracted with ethyl acetate 2~4 times, takes organic phase, obtains the second intermediate product；
Step 3, second intermediate product is washed with saturated sodium bicarbonate solution, saturated nacl aqueous solution successively, had no
Aqueous sodium persulfate dried process is removing moisture, then vacuum distillation goes out solvent, and carries out column chromatography for separation, and eluant, eluent is V dichloromethanes
Alkane: V ethyl acetate=50: 1, obtain pale yellowish oil liquid, i.e. 4- (4 '-trifluoromethyl) phenyl -2- -17 '-hydrazones of dehydroepiandros-sterone
Thiazole, its spectroscopic data：IR(KBr)v/cm-1：3431,2940,1728,1656,1556,1374,1322,1247,1125,
1068,705；1H NMR (600MHz, CDCl3)δ：0.94 (3H, s, 18-CH3), 1.05 (3H, s, 19-CH3), 3.51~3.57
(1H, m, 3-CαH), 5.37 (1H, d, J=4.8Hz, 6-CH), 6.94 (1H, s, Ar-H), 7.62 (2H, d, J=8.4Hz, Ph-
H), 7.87 (2H, d, J=8.4Hz, Ph-H)；13C NMR (150MHz, CDCl3)δ：17.0 (18-C), 19.5 (19-C), 20.6
(11-C), 23.7 (16-C), 26.0 (15-C), 31.4 (2-C), 31.5 (7-C), 31.7 (8-C), 34.1 (12-C), 36.7
(10-C), 37.3 (1-C), 42.3 (4-C), 44.5 (13-C), 50.5 (9-C), 54.0 (14-C), 71.8 (3-C), 105.5
(Ar-C), 121.2 (6-C), 125.7 (CF3), 126.1 (Ar-C), 141.1 (5-C), 149.8 (Ar-C), 152.0 (Ar-C),
165.7 (17-C), 169.9 (Ar-C), 171.3 (Ar-C)；HREIMS m/z：530.2447[M+H]+(calcd for
C29H34F3N3OS, 530.2455).
<Embodiment 2>
A kind of 4- (4 '-trifluoromethyl) phenyl -2- dehydroepiandros-sterone -17 '-hydrazone thiazoles, it has below formula：
A kind of preparation method of described 4- (4 '-trifluoromethyl) phenyl -2- dehydroepiandros-sterone -17 '-hydrazone thiazoles, including
Following steps：
Step one, dehydroepiandros-sterone 112mg is weighed, the bromo- 4 '-trifluoromethyl acetophenone 108mg of thiosemicarbazides 40mg, 2- put
In entering 100mL two-neck bottles, and add 15mL absolute ethyl alcohols to be completely dissolved it to it, microwave synthetic reaction is placed in after adding magneton
In device, temperature sensor is inserted, power is adjusted to 300W, preset temperature is 85 DEG C, TLC tracing detections, until raw material point base
Stop reaction after this disappearance.Room temperature is cooled to, the first intermediate product is obtained；
Step 2, the first intermediate product vacuum distillation is gone out most of solvent, add the mixing of 30mL distilled water, use second
Acetoacetic ester is extracted 3 times, takes organic phase, obtains the second intermediate product；
Step 3, second intermediate product is washed with saturated sodium bicarbonate solution, saturated nacl aqueous solution successively, had no
Aqueous sodium persulfate dried process is removing moisture, then vacuum distillation goes out solvent, and carries out column chromatography for separation, and eluant, eluent is V dichloromethanes
Alkane: V ethyl acetate=50: 1, obtain pale yellowish oil liquid, i.e. 4- (4 '-trifluoromethyl) phenyl -2- -17 '-hydrazones of dehydroepiandros-sterone
Thiazole, its spectroscopic data：IR(KBr)v/cm-1：3431,2940,1728,1656,1556,1374,1322,1247,1125,
1068,705；1H NMR (600MHz, CDCl3)δ：0.94 (3H, s, 18-CH3), 1.05 (3H, s, 19-CH3), 3.51~3.57
(1H, m, 3-CαH), 5.37 (1H, d, J=4.8Hz, 6-CH), 6.94 (1H, s, Ar-H), 7.62 (2H, d, J=8.4Hz, Ph-
H), 7.87 (2H, d, J=8.4Hz, Ph-H)；13C NMR (150MHz, CDCl3)δ：17.0 (18-C), 19.5 (19-C), 20.6
(11-C), 23.7 (16-C), 26.0 (15-C), 31.4 (2-C), 31.5 (7-C), 31.7 (8-C), 34.1 (12-C), 36.7
(10-C), 37.3 (1-C), 42.3 (4-C), 44.5 (13-C), 50.5 (9-C), 54.0 (14-C), 71.8 (3-C), 105.5
(Ar-C), 121.2 (6-C), 125.7 (CF3), 126.1 (Ar-C), 141.1 (5-C), 149.8 (Ar-C), 152.0 (Ar-C),
165.7 (17-C), 169.9 (Ar-C), 171.3 (Ar-C)；HREIMS m/z：530.2447[M+H]+(calcd for
C29H34F3N3OS, 530.2455).
<Embodiment 3>
A kind of 4- (4 '-trifluoromethyl) phenyl -2- dehydroepiandros-sterone -17 '-hydrazone thiazoles, it has below formula：
A kind of preparation method of described 4- (4 '-trifluoromethyl) phenyl -2- dehydroepiandros-sterone -17 '-hydrazone thiazoles, including
Following steps：
Step one, dehydroepiandros-sterone 120mg is weighed, the bromo- 4 '-trifluoromethyl acetophenone 120mg of thiosemicarbazides 45mg, 2- put
In entering 100mL two-neck bottles, and add 18mL absolute ethyl alcohols to be completely dissolved it to it, microwave synthetic reaction is placed in after adding magneton
In device, temperature sensor is inserted, power is adjusted to 350W, preset temperature is 90 DEG C, TLC tracing detections, until raw material point base
Stop reaction after this disappearance.Room temperature is cooled to, the first intermediate product is obtained；
Step 2, the first intermediate product vacuum distillation is gone out most of solvent, add the mixing of 35mL distilled water, use second
Acetoacetic ester is extracted 4 times, takes organic phase, obtains the second intermediate product；
Step 3, second intermediate product is washed with saturated sodium bicarbonate solution, saturated nacl aqueous solution successively, had no
Aqueous sodium persulfate dried process is removing moisture, then vacuum distillation goes out solvent, and carries out column chromatography for separation, and eluant, eluent is V dichloromethanes
Alkane: V ethyl acetate=50: 1, obtain pale yellowish oil liquid, i.e. 4- (4 '-trifluoromethyl) phenyl -2- -17 '-hydrazones of dehydroepiandros-sterone
Thiazole, its spectroscopic data：IR(KBr)v/cm-1：3431,2940,1728,1656,1556,1374,1322,1247,1125,
1068,705；1H NMR (600MHz, CDCl3)δ：0.94 (3H, s, 18-CH3), 1.05 (3H, s, 19-CH3), 3.51~3.57
(1H, m, 3-CαH), 5.37 (1H, d, J=4.8Hz, 6-CH), 6.94 (1H, s, Ar-H), 7.62 (2H, d, J=8.4Hz, Ph-
H), 7.87 (2H, d, J=8.4Hz, Ph-H)；13C NMR (150MHz, CDCl3)δ：17.0 (18-C), 19.5 (19-C), 20.6
(11-C), 23.7 (16-C), 26.0 (15-C), 31.4 (2-C), 31.5 (7-C), 31.7 (8-C), 34.1 (12-C), 36.7
(10-C), 37.3 (1-C), 42.3 (4-C), 44.5 (13-C), 50.5 (9-C), 54.0 (14-C), 71.8 (3-C), 105.5
(Ar-C), 121.2 (6-C), 125.7 (CF3), 126.1 (Ar-C), 141.1 (5-C), 149.8 (Ar-C), 152.0 (Ar-C),
165.7 (17-C), 169.9 (Ar-C), 171.3 (Ar-C)；HREIMS m/z：530.2447[M+H]+(calcd for
C29H34F3N3OS, 530.2455).
The form that the medicine can be made injection, tablet, pill, capsule, suspending agent or emulsion is used, its administration way
Footpath can be oral, or through subcutaneous, vein or intramuscular injection.
The chemical reaction of the preparation process is：
MW represents microwave reaction herein；
In order to illustrate effect of the invention, it is as follows that inventor provides experiment：
Experiment one
Using 4- of the present invention (4 '-trifluoromethyl) phenyl -2- -17 '-hydrazone of dehydroepiandros-sterone thiazoles to some tumours
Cell suppress the test result of growth of tumour cell proliferation activity experiment.Steroidal thiazolium compounds of the invention is selected to test
Its to human cervical carcinoma cell lines (HeLa), hepatoma cell strain (HEPG2), lung cancer cell line (A549), (human nasopharyngeal carcinoma is thin for CNE-2
Born of the same parents) and people's renal epithelial cell (HEK293T) cytotoxicity.Using MTT methods, vitro cytotoxicity measure is carried out.In 96 holes
In plate cultivate exponential phase cell in add various concentrations 4- (4 '-trifluoromethyl) phenyl -2- dehydroepiandros-sterones -17 ' -
Hydrazone thiazole, while carrying out 2 parallel tests, is compared with control group.After culture 72 hours, MTT is added, determine its extinction
Degree, calculates the concentration for suppressing growth of tumour cell propagation to compound when 50%, with IC respectively50Value is represented, as a result such as the institute of table 1
Show：
External antiproliferative activity (the IC of table 1 4- (4 '-trifluoromethyl) phenyl -2- dehydroepiandros-sterone -17 '-hydrazone thiazoles50, μ
mol/L)
| Compound number | HeLa | HepG2 | A549 | CNE-2 | HEK 293T |
| 1 | 13.2 | 11.3 | 8.3 | ND | ＞ 100 |
Wherein, ND is represented and not detected, compound 1 is 4- (4 '-trifluoromethyl) phenyl -2- dehydroepiandros-sterone -17 '-hydrazone thiophenes
Azoles, from table 1 4- (4 '-trifluoromethyl) phenyl -2- -17 '-hydrazone of dehydroepiandros-sterone thiazoles to human cervical carcinoma cell lines (HeLa),
The IC of hepatoma cell strain (HEPG2), lung cancer cell line (A549) and people's renal epithelial cell (HEK293T) inhibitory action50Value can be with
Find out, B- drop-cholestane benzimidazoles compound of the present invention is to human cervical carcinoma cell lines (HeLa), hepatoma cell strain
(HEPG2), lung cancer cell line (A549) these three tumour cells have good Developing restraint proliferation function, such as 4- (4 '-trifluoros
Methyl) phenyl -2- -17 '-hydrazone of dehydroepiandros-sterone thiazoles are to the suppression IC of hepatoma cell strain (HEPG2)50It is 11.3umol/L to be worth,
To the suppression IC of human cervical carcinoma cell lines (HeLa)50It is 13.2umol/L to be worth, and to the suppression of people's renal epithelial cell (HEK293T)
IC50Value is but more than 100, shows that the medicine has relatively low cytotoxicity to people's renal epithelial cell (HEK293T), while also illustrating
4- (4 '-trifluoromethyl) phenyl -2- -17 '-hydrazone of dehydroepiandros-sterone thiazoles have effective suppression to make in low concentration to cancer cell
With there is no drug damages to normal cell.It can be seen from the IC50 experiment values that upper table 1 is given, compound 4- (4 '-three
Methyl fluoride) phenyl -2- -17 '-hydrazone of dehydroepiandros-sterone thiazoles are to human cervical carcinoma cell lines (HeLa) hepatoma cell strain (HEPG2), lung
The growing multiplication of JEG-3 (A549) has good inhibiting effect.
Although embodiment of the present invention is disclosed as above, it is not restricted to listed fortune in description and embodiments
With, it can be applied to various suitable the field of the invention completely, for those skilled in the art, can be easily real
Now other modification, therefore under the universal limited without departing substantially from claim and equivalency range, the present invention is not limited to
Specific details and shown here as the embodiment with description.
Claims (8)
1. a kind of 4- (4'- trifluoromethyls) phenyl -2- dehydroepiandros-sterone -17'- hydrazone thiazoles, it is characterised in that it has followingization
Formula：
2. a kind of preparation of 4- as claimed in claim 1 (4'- trifluoromethyls) phenyl -2- dehydroepiandros-sterone -17'- hydrazone thiazoles
Method, it is characterised in that comprise the following steps：
Step one, take 100~120 parts of dehydroepiandros-sterones, 35~45 parts of thiosemicarbazides and 100~120 respectively by weight
The bromo- 4 '-trifluoromethyl acetophenone mixing of part 2-, and being added thereto to absolute ethyl alcohol is completely dissolved it, carries out microwave reaction, instead
Answer temperature for 80~90 DEG C, until reaction is completed, be cooled to room temperature, obtain the first intermediate product；
Step 2, by first intermediate product remove solvent, purification, in the material after purification add distilled water mix, then
It is extracted with ethyl acetate 2~4 times, takes organic phase, obtains the second intermediate product, wherein, the addition of distilled water is：Gone per 112mg
Hydrogen meter androsterone adds 25~35ml distilled water；
Step 3, second intermediate product is washed with saturated sodium bicarbonate solution, saturated nacl aqueous solution successively, and done
The mixture that dried process is obtained further is removed solvent by dry treatment to remove moisture, is purified, and carries out column chromatography for separation,
Obtain pale yellowish oil liquid, i.e. 4- (4'- trifluoromethyls) phenyl -2- dehydroepiandros-sterone -17'- hydrazone thiazoles.
3. the preparation method of 4- (4'- trifluoromethyls) phenyl -2- dehydroepiandros-sterone -17'- hydrazone thiazoles as claimed in claim 2,
Characterized in that, microwave power is 250~350W in the step one.
4. the preparation method of 4- (4'- trifluoromethyls) phenyl -2- dehydroepiandros-sterone -17'- hydrazone thiazoles as claimed in claim 2,
Characterized in that, the method for the removal solvent in the step 2 and step 3 is vacuum distillation.
5. the preparation method of 4- (4'- trifluoromethyls) phenyl -2- dehydroepiandros-sterone -17'- hydrazone thiazoles as claimed in claim 2,
Characterized in that, the dried process in the step 3 uses anhydrous sodium sulfate.
6. the preparation method of 4- (4'- trifluoromethyls) phenyl -2- dehydroepiandros-sterone -17'- hydrazone thiazoles as claimed in claim 2,
Characterized in that, column chromatography for separation in the step 3, eluant, eluent is VDichloromethane:VEthyl acetate=50:1.
7. a kind of purposes of 4- as claimed in claim 1 (4'- trifluoromethyls) phenyl -2- dehydroepiandros-sterone -17'- hydrazone thiazoles,
Its purposes is that 4- (4'- trifluoromethyls) phenyl -2- dehydroepiandros-sterone -17'- hydrazones thiazole is used to prepare treating cancer medicine
Application in thing.
8. the purposes of 4- (4'- trifluoromethyls) phenyl -2- dehydroepiandros-sterone -17'- hydrazone thiazoles as claimed in claim 7, wherein
Cancer includes：Liver cancer, lung cancer, stomach cancer, cervical carcinoma, prostate cancer and colon cancer.
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| CN105859821A (en) * | 2016-04-18 | 2016-08-17 | 广西师范学院 | 22-nor-stigmasta thiosemicarbazone compound and preparing method and application thereof |
| CN108218947B (en) * | 2018-02-05 | 2020-04-10 | 湖北省生物农药工程研究中心 | Steroid derivative containing thiazole heterocycle and preparation method and application thereof |
| CN108586566A (en) * | 2018-08-08 | 2018-09-28 | 齐齐哈尔医学院 | 3 beta-hydroxy -5 α, 8 α-peroxide androstane -6- alkene -17- (aromatic ring substitution) hydazone derivatives and preparation and application |
| CN115785189B (en) * | 2022-12-20 | 2023-08-25 | 齐齐哈尔医学院 | 5 alpha, 8 alpha-peroxosterol-17-phenylthiazole derivative and synthetic method and application thereof |
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| US20140235863A1 (en) * | 2011-06-03 | 2014-08-21 | Council Of Scientific & Industrial Research | Substituted 4-arylthiazoles and process of preparation thereof |
| CN103254264B (en) * | 2013-05-19 | 2016-04-06 | 广西师范学院 | Vitarrine aromatic aldehyde azine steroidal compounds and synthetic method thereof and preparing the application in antitumor drug |
| CN103242406B (en) * | 2013-05-19 | 2016-10-05 | 广西师范学院 | Dehydroepiandros-sterone aromatic aldehyde azine steroidal compounds and synthetic method thereof and the application in preparing antitumor drug |
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