CN105254699A - 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-sterone-17 '-hydrazone thiazole and its production and use.
Background technology
Cancer is a kind of principal disease of harm humans health, and capturing the difficult problem that malignant tumour is modern medicine, is also the challenge that medicine industry processed is maximum now.At present, various dissimilar antitumor drug constantly occurs and obtains application clinically, but the toxicity that the antitumor drug used clinically causes tissue due to it is comparatively large, greatly limit their use range.Therefore, the Main way that efficient, highly selective and the little cancer therapy drug of side effect are cancer therapy drug exploitations is found.
In antitumor drug, be used for the treatment of the medicine Finasteride of hyperplasia of prostate at present clinically, be used for the treatment of the medicine estramustine phosphate sodium (Estramustinephosphatesodium) of advanced prostate cancer, Abiraterone acetate and be used for the treatment of the medicine Exemestane of menopausal women mammary cancer, and recently by EntreMed company develop as monotherapy for the stable or multiple myeloma of recurrence and the cancer therapy drug methoxyestradiol (trade(brand)name: Panzem) of prostate cancer therapy, they all belong to steroidal antitumor drug.But at present there is complex structure in steroidal antitumor drug, and action site is many, causes for poor selectivity, and its mechanism of action, basic substance all do not have clear and definite theoretical explanation, thus structural formula, targeting all have can not be handling.
Summary of the invention
An object of the present invention is to solve at least the problems referred to above, and the advantage will illustrated at least is below provided.
A further object of the invention is to provide a kind of compound: 4-(4 '-trifluoromethyl) phenyl-2-dehydroepiandros-sterone-17 '-hydrazone thiazole, it has obvious restraining effect to various tumor cell strains such as liver cancer, lung cancer, cancer of the stomach, cervical cancer, prostate cancer, colorectal carcinomas, and toxicity is low, not easily produce resistance, present invention also offers preparation method and the purposes of this compound, this preparation method is simple, is conducive to marketing application.
In order to realize, according to these objects of the present invention and other advantage, providing a kind of 4-(4 '-trifluoromethyl) phenyl-2-dehydroepiandros-sterone-17 '-hydrazone thiazole, it has following chemical formula:
Described 4-(4 '-trifluoromethyl) phenyl-2-dehydroepiandros-sterone-17 ' preparation method of-hydrazone thiazole, comprise the following steps:
Step one, get the bromo-4 '-trifluoromethyl acetophenones mixing of 100 ~ 120 parts of dehydroepiandros-sterones, 35 ~ 45 parts of thiosemicarbazide and 100 ~ 120 parts of 2-respectively by weight, and add dehydrated alcohol wherein and make it dissolve completely, carry out microwave reaction, temperature of reaction is 80 ~ 90 DEG C, until reacted, be cooled to room temperature, obtain the first intermediate product;
Step 2, by described first intermediate product remove solvent, purify, to purify after material in add distilled water mixing, be extracted with ethyl acetate 2 ~ 4 times again, get organic phase, obtain the second intermediate product, wherein, the add-on of distilled water is: every 112mg dehydroepiandros-sterone adds 25 ~ 35ml distilled water;
Step 3, successively use saturated sodium bicarbonate solution, described second intermediate product of saturated nacl aqueous solution washing, and carry out drying treatment to remove moisture, mixture drying treatment obtained removes solvent further, purify, and carry out column chromatography for separation, obtain pale yellowish oil liquid, i.e. 4-(4 '-trifluoromethyl) phenyl-2-dehydroepiandros-sterone-17 '-hydrazone thiazole.
Preferably, the preparation method of described 4-(4 '-trifluoromethyl) phenyl-2-dehydroepiandros-sterone-17 '-hydrazone thiazole, in described step one, microwave power is 250 ~ 350W.
Preferably, the preparation method of described 4-(4 '-trifluoromethyl) phenyl-2-dehydroepiandros-sterone-17 '-hydrazone thiazole, the method for the removal solvent in described step one and step 3 is underpressure distillation.
Preferably, the preparation method of described 4-(4 '-trifluoromethyl) phenyl-2-dehydroepiandros-sterone-17 '-hydrazone thiazole, what the drying treatment in described step 3 adopted is anhydrous sodium sulphate.
Preferably, the preparation method of described 4-(4 '-trifluoromethyl) phenyl-2-dehydroepiandros-sterone-17 '-hydrazone thiazole, the method of having reacted is checked: by the mixture column chromatography chromatogram method tracking monitor in reaction, the then stopped reaction until the dehydroepiandros-sterone monitored in mixture disappears in described step one.
Preferably, the preparation method of described 4-(4 '-trifluoromethyl) phenyl-2-dehydroepiandros-sterone-17 '-hydrazone thiazole, column chromatography for separation in described step 4, eluent is V
methylene dichloride: V
ethyl acetate=50: 1.
A kind of purposes of described 4-(4 '-trifluoromethyl) phenyl-2-dehydroepiandros-sterone-17 '-hydrazone thiazole, its purposes is, described 4-(4 '-trifluoromethyl) phenyl-2-dehydroepiandros-sterone-17 '-hydrazone thiazole is for the preparation of the application in Therapeutic cancer medicine.
Preferably, the purposes of described 4-(4 '-trifluoromethyl) phenyl-2-dehydroepiandros-sterone-17 '-hydrazone thiazole, wherein cancer comprises: liver cancer, lung cancer, cancer of the stomach, cervical cancer, prostate cancer and colorectal carcinoma.
The present invention at least comprises following beneficial effect: provide a kind of compound: 4-(4 '-trifluoromethyl) phenyl-2-dehydroepiandros-sterone-17 '-hydrazone thiazole, its selectivity is high, to various tumor cell strains such as liver cancer, lung cancer, cancer of the stomach, cervical cancer, prostate cancer, colorectal carcinomas, there is obvious restraining effect, and toxicity is low, not easily produce resistance, greatly reduce the cytotoxic drugs that discharges to the injury of human body, present invention also offers preparation method and the purposes of this compound, this preparation method is simple, is conducive to marketing application.
Part is embodied by explanation below by other advantage of the present invention, target and feature, part also will by research and practice of the present invention by those skilled in the art is understood.
Embodiment
Below in conjunction with embodiment, the present invention is described in further detail, can implement according to this with reference to specification sheets word to make those skilled in the art.
Should be appreciated that used hereinly such as " to have ", other element one or more do not allotted in " comprising " and " comprising " term or the existence of its combination or interpolation.
< embodiment 1>
A kind of 4-(4 '-trifluoromethyl) phenyl-2-dehydroepiandros-sterone-17 '-hydrazone thiazole, it has following chemical formula:
Described 4-(4 '-trifluoromethyl) phenyl-2-dehydroepiandros-sterone-17 ' preparation method of-hydrazone thiazole, comprise the following steps:
Step one, weighing dehydroepiandros-sterone 100 ~ 120mg, thiosemicarbazide 35 ~ 45mg, bromo-4 '-trifluoromethyl acetophenone, the 100 ~ 120mg of 2-puts into 100mL two-neck bottle, and add 12 ~ 18mL dehydrated alcohol to it and make it dissolve completely, add magneton and be placed in Microwave synthesize reactor, insert temperature sensor, power is adjusted to 250 ~ 350W, preset temperature is 80 ~ 90 DEG C, TLC tracing detection, until raw material point substantially disappear after stopped reaction.Be cooled to room temperature, obtained the first intermediate product;
Step 2, described first intermediate product underpressure distillation is gone out most of solvent, add the mixing of 25 ~ 35mL distilled water, be extracted with ethyl acetate 2 ~ 4 times, get organic phase, obtain the second intermediate product;
Step 3, successively use saturated sodium bicarbonate solution, described second intermediate product of saturated nacl aqueous solution washing, and anhydrous sodium sulphate drying treatment is to remove moisture, underpressure distillation goes out solvent again, and carrying out column chromatography for separation, eluent is V methylene dichloride: V ethyl acetate=50: 1, obtains pale yellowish oil liquid, i.e. 4-(4 '-trifluoromethyl) phenyl-2-dehydroepiandros-sterone-17 '-hydrazone thiazole, its spectroscopic data: IR (KBr) v/cm-1:3431,2940,1728,1656,1556,1374,1322,1247,1125,1068,705,
1hNMR (600MHz, CDCl
3) δ: 0.94 (3H, s, 18-CH
3), 1.05 (3H, s, 19-CH
3), 3.51 ~ 3.57 (1H, m, 3-C
αh), 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),
13cNMR (150MHz, CDCl
3) 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), HREIMSm/z:530.2447 [M+H]
+(calcdforC
29h
34f
3n
3oS, 530.2455).
< embodiment 2>
A kind of 4-(4 '-trifluoromethyl) phenyl-2-dehydroepiandros-sterone-17 '-hydrazone thiazole, it has following chemical formula:
Described 4-(4 '-trifluoromethyl) phenyl-2-dehydroepiandros-sterone-17 ' preparation method of-hydrazone thiazole, comprise the following steps:
Step one, weighing dehydroepiandros-sterone 112mg, thiosemicarbazide 40mg, the bromo-4 '-trifluoromethyl acetophenone 108mg of 2-puts into 100mL two-neck bottle, and add 15mL dehydrated alcohol to it and make it dissolve completely, add magneton and be placed in Microwave synthesize reactor, insert temperature sensor, power is adjusted to 300W, preset temperature is 85 DEG C, TLC tracing detection, until raw material point substantially disappear after stopped reaction.Be cooled to room temperature, obtained the first intermediate product;
Step 2, described first intermediate product underpressure distillation is gone out most of solvent, add the mixing of 30mL distilled water, be extracted with ethyl acetate 3 times, get organic phase, obtain the second intermediate product;
Step 3, successively use saturated sodium bicarbonate solution, described second intermediate product of saturated nacl aqueous solution washing, and anhydrous sodium sulphate drying treatment is to remove moisture, underpressure distillation goes out solvent again, and carry out column chromatography for separation, eluent is V methylene dichloride: V ethyl acetate=50: 1, obtain pale yellowish oil liquid, i.e. 4-(4 '-trifluoromethyl) phenyl-2-dehydroepiandros-sterone-17 '-hydrazone thiazole, its spectroscopic data: IR (KBr) v/cm
-1: 3431,2940,1728,1656,1556,1374,1322,1247,1125,1068,705,
1hNMR (600MHz, CDCl
3) δ: 0.94 (3H, s, 18-CH
3), 1.05 (3H, s, 19-CH
3), 3.51 ~ 3.57 (1H, m, 3-C
αh), 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),
13cNMR (150MHz, CDCl
3) 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), HREIMSm/z:530.2447 [M+H]
+(calcdforC
29h
34f
3n
3oS, 530.2455).
< embodiment 3>
A kind of 4-(4 '-trifluoromethyl) phenyl-2-dehydroepiandros-sterone-17 '-hydrazone thiazole, it has following chemical formula:
Described 4-(4 '-trifluoromethyl) phenyl-2-dehydroepiandros-sterone-17 ' preparation method of-hydrazone thiazole, comprise the following steps:
Step one, weighing dehydroepiandros-sterone 120mg, thiosemicarbazide 45mg, the bromo-4 '-trifluoromethyl acetophenone 120mg of 2-puts into 100mL two-neck bottle, and add 18mL dehydrated alcohol to it and make it dissolve completely, add magneton and be placed in Microwave synthesize reactor, insert temperature sensor, power is adjusted to 350W, preset temperature is 90 DEG C, TLC tracing detection, until raw material point substantially disappear after stopped reaction.Be cooled to room temperature, obtained the first intermediate product;
Step 2, described first intermediate product underpressure distillation is gone out most of solvent, add the mixing of 35mL distilled water, be extracted with ethyl acetate 4 times, get organic phase, obtain the second intermediate product;
Step 3, successively use saturated sodium bicarbonate solution, described second intermediate product of saturated nacl aqueous solution washing, and anhydrous sodium sulphate drying treatment is to remove moisture, underpressure distillation goes out solvent again, and carry out column chromatography for separation, eluent is V methylene dichloride: V ethyl acetate=50: 1, obtain pale yellowish oil liquid, i.e. 4-(4 '-trifluoromethyl) phenyl-2-dehydroepiandros-sterone-17 '-hydrazone thiazole, its spectroscopic data: IR (KBr) v/cm
-1: 3431,2940,1728,1656,1556,1374,1322,1247,1125,1068,705,
1hNMR (600MHz, CDCl
3) δ: 0.94 (3H, s, 18-CH
3), 1.05 (3H, s, 19-CH
3), 3.51 ~ 3.57 (1H, m, 3-C
αh), 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),
13cNMR (150MHz, CDCl
3) 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), HREIMSm/z:530.2447 [M+H]
+(calcdforC
29h
34f
3n
3oS, 530.2455)..
The form that this medicine can make injection, tablet, pill, capsule, suspension agent or emulsion uses, and its route of administration can be oral, or through subcutaneous, vein or intramuscular injection.
The chemical reaction of this preparation process is:
MW represents microwave reaction herein;
In order to effect of the present invention is described, contriver provides experiment as follows:
Experiment one
Adopting 4-of the present invention (4 '-trifluoromethyl) phenyl-2-dehydroepiandros-sterone-17 '-hydrazone thiazole carries out the test result of inhibition tumor cell growing multiplication activity test to some tumour cell.Steroidal thiazolium compounds of the present invention is selected to test it to human cervical carcinoma cell lines (HeLa), hepatoma cell strain (HEPG2), lung cancer cell line (A549), the cytotoxicity of CNE-2 (KB cell) and people's renal epithelial cell (HEK293T).Adopt MTT method, carry out vitro cytotoxicity mensuration.4-(4 '-trifluoromethyl) phenyl-2-dehydroepiandros-sterone-17 of different concns is added in the logarithmic phase cell cultivated in 96 orifice plates '-hydrazone thiazole, carries out 2 parallel tests simultaneously, compares with control group.Cultivate after 72 hours, add MTT, measure its absorbancy, calculate respectively inhibition tumor cell growing multiplication to 50% time compound concentration, with IC
50value represents, result is as shown in table 1:
Table 14-(4 '-trifluoromethyl) phenyl-2-dehydroepiandros-sterone-17 ' the In Vitro Anti proliferation activity (IC of-hydrazone thiazole
50, μm ol/L)
| Compound number | HeLa | HepG2 | A549 | CNE-2 | HEK 293T |
| 1 | 13.2 | 11.3 | 8.3 | ND | ＞100 |
Wherein, ND representative does not detect, compound 1 is 4-(4 '-trifluoromethyl) phenyl-2-dehydroepiandros-sterone-17 '-hydrazone thiazole, 4-(4 '-trifluoromethyl) phenyl-2-dehydroepiandros-sterone-17 from table 1 '-hydrazone thiazole to human cervical carcinoma cell lines (HeLa), hepatoma cell strain (HEPG2), lung cancer cell line (A549) and people's renal epithelial cell (HEK293T) inhibiting IC
50value can be found out, B-of the present invention falls-and cholestane benzimidazoles compound is to human cervical carcinoma cell lines (HeLa), these three kinds of tumour cells of hepatoma cell strain (HEPG2), lung cancer cell line (A549) have good Developing restraint proliferation function, as 4-(4 '-trifluoromethyl) phenyl-2-dehydroepiandros-sterone-17 '-hydrazone thiazole is to the suppression IC of hepatoma cell strain (HEPG2)
50value is 11.3umol/L, to the suppression IC of human cervical carcinoma cell lines (HeLa)
50value is 13.2umol/L, and the suppression IC to people's renal epithelial cell (HEK293T)
50value is but greater than 100, show that this medicine has lower cytotoxicity to people's renal epithelial cell (HEK293T), simultaneously 4-(4 '-trifluoromethyl) phenyl-2-dehydroepiandros-sterone-17 being also described '-hydrazone thiazole all has effective restraining effect when lower concentration to cancer cells, to normal cell based, this do not have drug damages.According to the IC50 experimental value that upper table 1 provides, compound 4-(4 '-trifluoromethyl) phenyl-2-dehydroepiandros-sterone-17 ' growing multiplication of-hydrazone thiazole to human cervical carcinoma cell lines (HeLa) hepatoma cell strain (HEPG2), lung cancer cell line (A549) have good restraining effect.
Although embodiment of the present invention are open as above, but it is not restricted to listed in specification sheets and embodiment utilization, it can be applied to various applicable the field of the invention completely, for those skilled in the art, can easily realize other amendment, therefore do not deviating under the universal that claim and equivalency range limit, the present invention is not limited to specific details and illustrates here and the embodiment described.
Claims (9)
1. 4-(4 '-trifluoromethyl) phenyl-2-dehydroepiandros-sterone-17 '-hydrazone thiazole, it is characterized in that, it has following chemical formula:
2. a preparation method for 4-as claimed in claim 1 (4 '-trifluoromethyl) phenyl-2-dehydroepiandros-sterone-17 '-hydrazone thiazole, is characterized in that, comprise the following steps:
Step one, get the bromo-4'-trifluoromethyl acetophenones mixing of 100 ~ 120 parts of dehydroepiandros-sterones, 35 ~ 45 parts of thiosemicarbazide and 100 ~ 120 parts of 2-respectively by weight, and add dehydrated alcohol wherein and make it dissolve completely, carry out microwave reaction, temperature of reaction is 80 ~ 90 DEG C, until reacted, be cooled to room temperature, obtain the first intermediate product;
Step 2, by described first intermediate product remove solvent, purify, to purify after material in add distilled water mixing, be extracted with ethyl acetate 2 ~ 4 times again, get organic phase, obtain the second intermediate product, wherein, the add-on of distilled water is: every 112mg dehydroepiandros-sterone adds 25 ~ 35ml distilled water;
Step 3, successively use saturated sodium bicarbonate solution, described second intermediate product of saturated nacl aqueous solution washing, and carry out drying treatment to remove moisture, mixture drying treatment obtained removes solvent further, purify, and carry out column chromatography for separation, obtain pale yellowish oil liquid, i.e. 4-(4 '-trifluoromethyl) phenyl-2-dehydroepiandros-sterone-17 '-hydrazone thiazole.
3. the preparation method of 4-(4 '-trifluoromethyl) phenyl-2-dehydroepiandros-sterone-17 '-hydrazone thiazole as claimed in claim 2, it is characterized in that, in described step one, microwave power is 250 ~ 350W.
4. the preparation method of 4-(4 '-trifluoromethyl) phenyl-2-dehydroepiandros-sterone-17 '-hydrazone thiazole as claimed in claim 2, is characterized in that, the method for the removal solvent in described step one and step 3 is underpressure distillation.
5. the preparation method of 4-(4 '-trifluoromethyl) phenyl-2-dehydroepiandros-sterone-17 '-hydrazone thiazole as claimed in claim 2, is characterized in that, what the drying treatment in described step 3 adopted is anhydrous sodium sulphate.
6. the preparation method of 4-(4 '-trifluoromethyl) phenyl-2-dehydroepiandros-sterone-17 '-hydrazone thiazole as claimed in claim 2, it is characterized in that, the method of having reacted is checked: by the mixture column chromatography chromatogram method tracking monitor in reaction, the then stopped reaction until the dehydroepiandros-sterone monitored in mixture disappears in described step one.
7. the preparation method of 4-(4 '-trifluoromethyl) phenyl-2-dehydroepiandros-sterone-17 '-hydrazone thiazole as claimed in claim 2, it is characterized in that, column chromatography for separation in described step 4, eluent is V
methylene dichloride: V
ethyl acetate=50: 1.
8. the purposes of 4-as claimed in claim 1 or 2 (4 '-trifluoromethyl) phenyl-2-dehydroepiandros-sterone-17 '-hydrazone thiazole, its purposes is, described 4-(4 '-trifluoromethyl) phenyl-2-dehydroepiandros-sterone-17 '-hydrazone thiazole is for the preparation of the application in Therapeutic cancer medicine.
9. the purposes of 4-(4 '-trifluoromethyl) phenyl-2-dehydroepiandros-sterone-17 '-hydrazone thiazole as claimed in claim 8, wherein cancer comprises: liver cancer, lung cancer, cancer of the stomach, cervical cancer, prostate cancer and colorectal carcinoma.
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| CN108218947A (en) * | 2018-02-05 | 2018-06-29 | 湖北省生物农药工程研究中心 | A kind of steroid derivative containing thiazole heterocycle and preparation method and application |
| 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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| 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 |
| CN108218947A (en) * | 2018-02-05 | 2018-06-29 | 湖北省生物农药工程研究中心 | A kind of steroid derivative containing thiazole heterocycle and preparation method and application |
| 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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| CN105254699B (en) | 2017-05-17 |
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