CN103204892A - Beta-norcholest-6-(4'-phenyl)-aminothizone compound and synthesis method and application thereof in preparing antitumor drug - Google Patents
Beta-norcholest-6-(4'-phenyl)-aminothizone compound and synthesis method and application thereof in preparing antitumor drug Download PDFInfo
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- CN103204892A CN103204892A CN2013101618562A CN201310161856A CN103204892A CN 103204892 A CN103204892 A CN 103204892A CN 2013101618562 A CN2013101618562 A CN 2013101618562A CN 201310161856 A CN201310161856 A CN 201310161856A CN 103204892 A CN103204892 A CN 103204892A
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- 0 CCCC(CC(*)C*C)(C(CC1)C(C)[C@@](C)C(N)=*C2CCC2)[C@]1[C@](C)CCCCCC(C)C Chemical compound CCCC(CC(*)C*C)(C(CC1)C(C)[C@@](C)C(N)=*C2CCC2)[C@]1[C@](C)CCCCCC(C)C 0.000 description 9
- PFBNMNYLRNPKSK-UHFFFAOYSA-N C=C(C=C(C=C1)N)C=C1I Chemical compound C=C(C=C(C=C1)N)C=C1I PFBNMNYLRNPKSK-UHFFFAOYSA-N 0.000 description 1
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Abstract
The invention relates to a Beta-norcholest-6-(4'-phenyl)-aminothizone compound. The chemical structural formula of the Beta-norcholest-6-(4'-phenyl)-aminothizone compound is shown as the specification. Experiments prove that the Beta-norcholest-6-(4'-phenyl)-aminothizone compound has obvious inhibition effects on many tumor cell strains and can be applied to preparation of medicaments for treating cancers.
Description
One, technical field
The present invention relates to B-falls-courage steroid-6-(4'-phenyl class)-contracting ammonia sulphur hydrazone compound and synthetic method and the application in the preparation antitumor drug.
Two, background technology
Cancer is a kind of malignant tumour, is one of disease to human health and quality of life harm maximum.Seeking efficient, highly selective and the little antitumor drug of side effect is the main direction of medicament research and development.
In antitumor drug, the medicine Finasteride that is used for the treatment of hyperplasia of prostate that Merck in 1992 lists a company belongs to the steroidal amides.In recent years in the research of antitumor drug, there are some to have the report that steroidal compounds falls in B-, for example compound Orostanal can inducing leukemia HL-60 apoptosis (Tomofumi Miyamoto, Kota Kodama, Yuko Aramaki, Ryuichi Higuchi, Rob W.M.Van Soest, Orostanal, a novel abeo-sterol inducing apoptosis in leukemia cell from a marine sponge, Stelletta hiwasaensis, Tetrahedron Letters2001 (42): 6349-6351; Bo Liu, Wei-Shan Zhou, The first stereoselective synthesis of orostanal isolated from a marine sponge Stelletta hiwasaenis, Tetrahedron, 2003 (59): 3379-3384), some above-mentioned compound growing multiplication to some tumour cell in external or body has remarkable restraining effect.
We once provided application for a patent for invention (Chinese invention patent, the application number: 200810073497.4 of a class " 3,6-di-substituted sterides oxime compounds is as antitumor drug "; Publication number: CN101245090A), the while also has been relevant report (Jianguo Cui, Liliang Huang, Lei Fan, Aimin Zhou, Steroids, 2008,73 (3): 252 – 256; Jian-Guo Cui, Lei Fan, Li-Liang Huang, Hong-Li Liu, Ai-Min Zhou.Steroids, 2009,74 (1), 62-72; Jianguo Cui, Lei Fan, Yanmin Huang, Yi Xin, Aimin Zhou, Steroids.2009,74 (12), 989-995).In addition, we also provide the patent of invention (Chinese invention patent of a class " 6-replacement-4-azepine-A-homo-3-oxo steroidal compounds and the application in the preparation antitumor drug thereof ", the patent No.: ZL201010107528.0) and application for a patent for invention (Chinese patent, the application number: 201110009124.2.) of another kind of " 3-replacements-B-Homo-steroidal-B-cyclic lactam compound and preparation method thereof and the application in preparing antitumor drug ".Simultaneously, we have obtained one " B-falls-3; 6-two replaces cholestane compound and preparation method thereof and the application in the preparation antitumor drug " and have authorized (the patent No.: ZL20111079146.3), and delivered relevant report (Chunfang Gan, Lianghua Fan, Jianguo Cui, Yanmin Huang, Yanxiao Jiao, Wanxin Wei, Synthesis of novel ring B abeo-sterol derivatives and their antiproliferative activities.Steroids, 2012 (77): 1061-1068; Gan Chunfang, Li Weiyu, woods Kai good fortune, the synthetic of androstane and anti-tumor activity research, chemical reagent, 2013 (35): 218-222) fall in Huang Yanmin, Cui Jianguo, B-.
Three, summary of the invention
The purpose of this invention is to provide a class B-falls-courage steroid-6-(4 '-the phenyl class)-contracting ammonia sulphur hydrazone compound and synthetic method and the application in the preparation antitumor drug.
The present invention is achieved through the following technical solutions above-mentioned purpose: a class B-falls-courage steroid-6-(4'-phenyl class)-contracting ammonia sulphur hydrazone compound comprises: B-falls-3 beta-acetoxyl group-5s-hydroxyl-courage steroid-6-(4 '-phenyl) contracting ammonia sulphur hydrazone (1), B-falls-courage steroid-3 β, 5 beta-dihydroxyies-courage steroid-6-(4 '-phenyl) contracting ammonia sulphur hydrazone (2), B-fall-3 beta-acetoxyl group-5 beta-hydroxy-courage steroid-6-[4 '-(2 ' ', 4 ' '-dichlorophenyl)]-contracting ammonia sulphur hydrazone (3),-3 β fall in B-, 5 beta-dihydroxyies-courage steroid-6-[4 '-(2 ' ', 4 ' '-dichlorophenyl)] contracting ammonia sulphur hydrazone (4), B-falls-3 beta-acetoxyl group-5s-hydroxyl courage steroid-6-[4 '-(2 ' '-aminomethyl phenyl)] contracting ammonia sulphur hydrazone (5),-3 β fall in B-, 5 beta-dihydroxyl courage steroid-6-[4 '-(2 ' '-aminomethyl phenyl)] contracting ammonia sulphur hydrazone (6) concrete structure formula is as follows:
Compound 2 of the present invention, 4,6 can be sloughed 3-ethanoyl base by compound 1,3,5 and obtain.
From middle product (3) 3-acetoxyl group-5-hydroxyl-7-formyl cholestane, press following chemical equation synthesising target compound 1-6:
The per-cent % of indication of the present invention unless otherwise indicated is mass percent %.
Suppress activity test by cancer cell in vitro and show that cancer cell strains such as the various tumor cell strains of compound 1-6 of the present invention such as liver cancer, cancer of the stomach, nasopharyngeal carcinoma have significant inhibitory effect.Compound 1-6 of the present invention can be used for preparing the medicine for the treatment of cancer.
Four, embodiment
The invention will be further described by the following examples.
Embodiment
The preparation method of intermediate product
Intermediate product (1)
Take by weighing 5.018g, the cholesterol of 13mmol is dissolved in the 40mL pyridine, after the dissolving fully, slowly drips the 4.0mL diacetyl oxide, after diacetyl oxide adds, continues to stir 0.5 hour, then reactant is left standstill 24h under room temperature.Adding distil water 15mL with 10mL * 3 ethyl acetate extractions, uses 1mol.L respectively again
-1Dilute hydrochloric acid is washed, saturated NaHCO
3Solution 10mL washes 1 time, and washing 10mL * 3 are washed to neutrality with saturated common salt at last.Anhydrous sodium sulfate drying filters, and decompression steams solvent, when relatively large solid is separated out, stops distillation, and the solid that heating for dissolving is separated out leaves standstill and allows it separate out crystallization.Obtain white plates crystal 1 5.308g after suction filtration and the drying, productive rate 96%.Product structure is analyzed definite through IR, NMR and MS.
Intermediate product (2)
Take by weighing 110mg intermediate product 1 and pack in the reaction flask, add 16mL methylene dichloride and 4mL methyl alcohol.Place the ethyl acetate vacuum flask of cooled with liquid nitrogen, when treating that system temperature is cooled to-78 ℃, feed and be rich in O
3Oxygen Flow, after reaction is finished, add the 2mL dimethyl sulphide, be warming up to stirred overnight at room temperature.Decompression extracts most of solvent and obtains oily matter, and this oily matter adds the layering of 10mL distilled water with the dissolving of 50mL methylene dichloride, tells the organic layer anhydrous sodium sulfate drying.Decompression extracts solvent, obtains water white oily matter, drying.Use V
Sherwood oil: V
Ethyl acetateThe eluent rapid column chromatography of=4:1 separates, and obtains oily compound 2 108mg, productive rate 91%.Product structure is analyzed definite through IR, NMR and MS.
Intermediate product (3)
Take by weighing 478mg intermediate product 2 in the 100mL round-bottomed flask, add 22mL benzene and 4.78g neutral alumina, stirring reaction 24h under the room temperature does not have stopped reaction behind the raw material, in this mixture impouring silica gel short column, with a large amount of CH
2Cl
2Flushing until no product point, extracts solvent and obtains transparent oily matter 445mg.The silica gel column chromatography separation obtains white solid compound 3 377mg, productive rate 85%.Product structure is analyzed definite through IR, NMR and MS.
Embodiment 2
B-falls-preparation of courage steroid-6-(4'-phenyl class)-contracting ammonia sulphur hydrazone compound
B-falls-3 beta-acetoxyl group-5s-hydroxyl-courage steroid-6-(4 '-phenyl)-contracting ammonia sulphur hydrazone (1)
Take by weighing 196mg, the intermediate product of 0.426mmol (3) is dissolved in the 55mL dehydrated alcohol, regulates pH with Glacial acetic acid and is about 4, adds 94mg then, and the benzene of 0.562mmol places 60 ℃ of oil bath stirring reaction 2.5h for thiosemicarbazide, uses V
Methylene dichloride: V
Methyl alcoholThe developping agent of=50:1 carries out TCL and follows the tracks of reaction, no raw material point back stopped reaction.Removal of solvent under reduced pressure with ethyl acetate 20mL * 3 extractions, merges organic layer, respectively washes 1 time the organic layer anhydrous sodium sulfate drying respectively with saturated aqueous common salt 10mL, saturated sodium bicarbonate solution 10mL.Filter, removal of solvent under reduced pressure obtains the yellow oily mixture.Carry out column chromatography for separation with silica gel H, eluent V
Methylene dichloride: V
Methyl alcohol=50:1 obtains yellow solid 1 226mg, productive rate: 87.1%; M.p.:92-94 ℃; The spectroscopic data of compound 9: IR (KBr) v (cm
-1): 3432,3309,2950,2864,1728,1593,1540,1499,1438,1395,1254,1197,1062,1017,935.
1H NMR (CDCl
3, 300MHz) δ: 9.782 (1H, s, NH), 9.147 (1H, s ,-NH), 7.657 (1H, d, J=7.5Hz, C
6-H), and 7.42-7.14 (5H, m, Ar-H), 5.19-5.07 (1H, m, C
3-H), 2.064 (3H, s, CH
3CO), 0.700 (3H, s, 18-CH
3), 0.972 (3H, s, 19-CH
3), 0.929 (3H, d, J=6.3Hz, 21-CH
3), 0.875 (3H, d, J=6.6Hz, 26or27CH
3), 0.872 (3H, d, J=6.6Hz, 26or27CH
3);
13CNMR (CDCl
3, 75MHz): 177.5 (C=S), 170.2 (C=O), 149.8 (6-C), 138.0 (Ar-C), 128.6 (Ar-C), 127.8 (Ar-C), 124.2 (Ar-C), 83.1 (5-C), 70.1 (3-C), 56.4 (7-C), 55.9 (14-C), 55.5 (17-C) 52.7 (9-C), 45.2 (13-C), 44.6 (10-C), 42.8 (8-C), 40.9 (12-C), 39.6 (24-C), 39.5 (22-C), 36.2 (4-C), 35.6 (20-C), 29.9 (1-C), 28.6 (16-C), 28.0 (25-C), 24.9 (2-C), 24.8 (15-C), 23.8 (23-C), 22.6 (27-C), 21.7 (26-C), 21.5 (11-C), 20.8 (2 '-C), 18.8 (21-C), 18.4 (19-C), 12.5 (18-C); HREIMS m/z:610.4038[M+H]
+. (calcd. for C
36H
56N
3O
3S, 610.4042)
B-falls-courage steroid-3 β, 5 beta-dihydroxyies-courage steroid-6-(4 '-phenyl)-contracting ammonia sulphur hydrazone (2)
Take by weighing 182mg, the compound 1 of 0.31mmol is dissolved in CH
3Among the OH, add 13%K
2CO
3Solution 2mL does not have raw material point stopped reaction in 30 ℃ of following stirring reaction 0.5h, uses V
Ethyl acetate: V
Sherwood oil=1:4 developping agent carries out TLC and follows the tracks of reaction,, removal of solvent under reduced pressure.Add less water and use ethyl acetate extraction 15mL * 3 then, organic layer is washed with saturated common salt 10mL * 2, and anhydrous sodium sulfate drying obtains compound 136mg, productive rate: 81.1%; M.p.:99-103 ℃.The spectroscopic data of compound 2: IR (KBr) v (cm
-1): 3416,3322,2993,2860,1593,1540,1491,1422,1377,1324,1254,1201,1070,1009,948.
1H NMR (CDCl
3, 300MHz) δ: 9.661 (1H, s, NH), 9.118 (1H, s, NH), 7.580 (1H, d, J=8.8Hz, C
6-H), and 7.38-7.09 (5H, m, Ar-H), 0.718 (3H, s, 18-CH
3), 3.44-3.12 (1H, m, C
3-H), 0.968 (3H, s, 19-CH
3), 0.950 (3H, d, J=5.7Hz, 21-CH
3), 0.879 (3H, d, J=6.6Hz, 26or27CH
3), 0.875 (3H, d, J=6.6Hz, 26or27CH
3);
13C NMR (CDCl
3, 75MHz) δ: 177.3 (C=S), 149.9 (6-C), 138.0 (Ar-C), 128.4 (Ar-C), 125.5 (Ar-C), 124.3 (Ar-C), 84.5 (5-C), 67.4 (3-C), 56.3 (7-C), 55.6 (14-C), 52.0 (17-C) 51.9 (9-C), 45.5 (13-C), 44.8 (10-C), 43.5 (8-C), 43.0 (12-C), 39.7 (24-C), 39.5 (22-C), 36.2 (4-C), 35.6 (20-C), 28.5 (1-C), 28.1 (16-C), 28.0 (25-C), 27.5 (2-C), 24.7 (15-C), 23.8 (23-C), 22.8 (27-C), 22.5 (26-C), 21.6 (11-C), 18.8 (21-C), 18.5 (19-C), 12.5 (18-C) .HREIMS m/z:568.4121[M+H]
+, (calcd.for C
34H
54N
3O
2S, 568.3937)
-3 beta-acetoxyl group-5 beta-hydroxy-courage steroid-6-[4 '-(2,4 dichloro benzene base) falls in B-]-contracting ammonia sulphur hydrazone (3)
The preparation method of compound 3 and compound 1 are similar, adopt raw material 4-(2 ', 4 '-dichlorobenzene)-the 3-thiosemicarbazide replaces benzene for thiosemicarbazide, productive rate 90.4%.m.p.:91-93℃。IR(KBr)v(cm
-1):3457,3289,2950,2860,1723,1581,1536,1454,1368,1311,1258,1185,1099,1054,1013,935,857,813,
1HNMR(CDCl
3,300MHz)δ:9.759(1H,s,NH),9.491(1H,s,NH),8.533(1H,d,J=9Hz,Ar-H),7.424(1H,d,J=2.4Hz,Ar-H),7.328(1H,d,J=7.2Hz,C
6-H),7.252(1H,d,J=2.1Hz,Ar-H),5.21-5.07(1H,m,C
3-H),2.068(1H,s,3-CH
3CO),0.969(1H,s,19-CH
3),0.920(1H,d,J=6.3Hz,21-CH
3),0.870(1H,d,J=6.6Hz,26or27CH
3),0.867(1H,d,J=6.6Hz,26or27CH
3),0.680(3H,s,18-CH
3);
13CNMR(CDCl
3,75MHz)δ:175.0(C=S),170.0(C=O),150.1(C=N),133.9(Ar-C),130.6(Ar-C),128.9(Ar-C),127.2(Ar-C),127.0(Ar-C),126.01(Ar-C),83.1(5-C),70.1(3-C),56.5(7-C),56.0(14-C),55.4(17-C),53.5(9-C)52.6(7-C),45.3(10-C),44.6(13-C),42.7(8-C),41.1(24-C),39.5(12-C),39.5(4-C),36.2(22-C),35.6(20-C),29.5(2-C),28.6(1-C),28.0(25-C),24.8(16-C),23.8(15-C),22.8(23-C),22.6(11-C),21.6(26-C?and27-C),21.5(2’-C),18.8(21-C),18.4(19-C),12.5(18-C);HREIMS?m/z:678.3525[M+H]
+,(calcd.for?C
36H
54Cl
2N
3O
3,678.3263)。
-3 β fall in B-, 5 beta-dihydroxyies-courage steroid-6-[4-(2,4 dichloro benzene)]-contracting ammonia sulphur hydrazone (4)
Synthetic method is similar to compound 2, adopts starting compound 3, obtains the productive rate 91.5% of compound 4, m.p.:101-105 ℃.IR(KBr)v(cm
-1):3374,2942,2876,1536,1466,1377,1315,1274,1193,1099,1078,1009,935,861,808;
1H?NMR(CDCl
3,300MHz)δ:9.872(1H,s,-NH),9.500(1H,s,-NH),8.475(1H,d,J=9Hz,Ar-H),7.403(1H,d,J=7.5Hz,Ar-H),7.372(1H,d,J=7.5Hz,C
6-H),7.180(1H,d,J=8.7Hz,Ar-H),4.20-4.31(1H,m,C
3-H),0.962(3H,s,19-CH
3),0.926(3H,d,J=6.3Hz,21-CH
3),0.877(3H,d,J=6.6,26or27CH
3),0.873(3H,d,J=6.6Hz,26or27CH
3),0.699(3H,s,18-CH
3);?
13C?NMR(CDCl
3,75MHz)δ:174.8(C=S),150.5(6-C),133.9(Ar-C),130.4(Ar-C),128.8(Ar-C),127.0(Ar-C),126.9(Ar-C),125.7(Ar-C),84.2(5-C),67.2(3-C),60.4(7-C),56.4(14-C),55.6(17-C)53.4(9-C),51.6,45.5(13-C),44.8(10-C),43.6(8-C),42.9(12-C),39.7(24-C),39.5(22-C),36.2(4-C),35.6(20-C),31.9,28.5(1-C),28.0(16-C),27.8(25-C),27.6(2-C),24.6(15-C),23.8(23-C),22.8(27-C),22.7(23-C),22.6(11-C),21.6(26-C?and27-C),18.8(21-C),18.6(19-C),12.6(18-C).HREIMS?m/z:636.3365[M+H]
+,(calcd.for?C
34H
52Cl
2N
3O
2S636.3187)。
B-falls-3 beta-acetoxyl group-5s-hydroxyl courage steroid-6-[4 '-(2-aminomethyl phenyl)]-preparation of contracting ammonia sulphur hydrazone (5)
The preparation method of compound 5 and compound 1 are similar, adopt raw material 4-(2 '-methyl) phenyl amino thiocarbamide to replace benzene for thiosemicarbazide, productive rate: 97%, m.p.:84-91 ℃.The spectroscopic data of compound 5: IR (KBr) ν/cm
-1: 3460,3330,2949,2868,1732,1527,1454,1384,1258,1217,1180,1078,1017,735;
1H NMR (300MHz, CDCl
3) δ: 0.690 (1H, s, 18-CH
3), 0.868 (3H, d, J=6.3,26-CH
3Or27-CH
3), 0.889 (3H, d, J=6.3,26-CH
3Or27-CH
3), 0.930 (3H, d, J=6.0,21-CH
3), 0.974 (3H, s, 19-CH
3), 2.048 (3H, s, 2 '-CH
3), 2.305 (3H, s, 3-CH
3), 7.780 (1H, d, J=7.2, C
6-H), 7.396-7.090 (4H, m, Ar-H), 8.896 (1H, s, NH), 10.003 (1H, s, NH);
13C NMR (75MHz, CDCl
3) δ: 176.5 (C=S), 170.2 (Ar-C), 149.3 (Ar-C), 136.5 (Ar-C), 133.8 (6-C=N), 130.5 (Ar-C), 127.3 (Ar-C), 127.0 (Ar-C), 126.2 (Ar-C), 83.0 (5-C), 70.0 (CH
3-Ar), 56.5 (14-C), 56.0 (17-C), 55.5 (9-C), 45.2 (13-C), 44.6 (10-C), 42.8 (8-C), 41.1 (24-C), 39.5 (12-C), 36.2 (22-C), 35.6 (20-C), 30.0 (2-C), 28.6 (1-C), 28.0 (25-C), 24.9 (16-C), 23.8 (15-C), 22.8 (23-C), 22.6 (11-C), 21.7 (26-C and27-C), 21.5 (2 '-C), 18.8 (21-C), 18.5 (19-C), 18.0,12.5 (18-C).
-3 β fall in B-, 5 beta-dihydroxyl courage steroid-6-[4 '-(2-aminomethyl phenyl)]-preparation of contracting ammonia sulphur hydrazone (6)
Synthetic method is similar to compound 2, adopts starting compound 5, productive rate: 97%, m.p.:104-106 ℃. the spectroscopic data of compound 6: IR (KBr) ν/cm
-1: 3411,3338,2937,2868,1593,1531,1454,1392,1184,1111,1074,735;
1H NMR (300MHz, CDCl
3) δ: 0.710 (3H, s, 18-CH
3), 0.882 (3H, d, J=6.6,26-CH
3Or27-CH
3), 0.885 (3H, d, J=6.6,26-CH
3Or27-CH
3), 0.936 (3H, d, J=6.3,21-CH
3), 0.972 (3H, s, 19-CH
3), 2.289 (3H, s.9 '-CH
3), 4.289-4.176 (1H, m, C
3-H), 7.253-7.157 (4H, m, C
5 '-9 '-H), 8.887 (1H, s ,-NH), 10.052 (1H, s ,-NH).
13C NMR (75MHz, CDCl
3) δ: 176.3 (C=S), 150.1 (Ar-C), 136.5 (Ar-C), 133.6 (6-C=N), 130.5 (Ar-C), 127.2 (Ar-C), 126.8 (Ar-C), 126.2 (Ar-C), 84.1 (5-C), 67.3 (3-C), 56.4 (14-C), 56.3 (17-C), 55.5 (9-C), 45.5 (13-C), 44.8 (10-C), 43.5 (8-C), 42.9 (24-C), 39.5 (12-C), 36.2,35.6 (20-C), 28.5 (1-C), 28.2,28.0 (25-C), 27.5,24.7 (16-C), 23.8 (15-C), 22.8 (23-C), 22.6 (11-C), 21.7 (26-C and27-C), 18.8 (21-C), 18.5 (19-C), 12.5 (18-C).
Embodiment 3
Present embodiment is to adopt compound of the present invention that some tumour cell is carried out the activity test of extracorporeal suppression tumor cell growing multiplication.
Adopt compound of the present invention to stomach cancer cell line SGC7901, human hepatoma cell strain Bel7404, human body human nasopharyngeal epithelioma 1 CNE carries out the activity test of extracorporeal suppression tumor cell growing multiplication.Adopt the MTT method, carry out the activity test of extracorporeal suppression tumor cell growing multiplication.Add the compound of different concns in the logarithmic phase cell of in 96 orifice plates, cultivating, carry out 3 parallel tests simultaneously, compare with control group, after cultivating 72h, add MTT, measure its absorbancy, calculate respectively and suppress growth of tumour cell to 50% o'clock compound concentrations, with IC
50Value representation.Wherein compound 1,3, and the vitro cytotoxicity of 6 pairs of above-mentioned three kinds of tumor cell lines is as shown in table 1:
Table 1B-falls-courage steroid-6-(4'-phenyl class)-contracting ammonia sulphur hydrazone compound anti tumor activity in vitro test result (MTT method, IC
50, μ mol/L)
Listed compound is to human hepatoma cell, cervical cancer cell, the inhibiting IC of stomach cancer cell from table 1
50Value as can be seen, B-of the present invention falls-courage steroid-6-(4'-phenyl class)-contracting ammonia sulphur hydrazone compound has the good restraining effect to these three kinds of tumour cells, as the inhibition IC of 6 couples of human hepatoma cell strain Bel7404 of compound
50Value is 3.7 μ mol/L, to the inhibition IC of human nasopharyngeal epithelioma 1 CNE
50Value is 6.4 μ mol/L.
Claims (4)
1. a class B-falls-courage steroid-6-(4 '-phenyl class) contracting ammonia sulphur hydrazone steroidal compounds, it is characterized in that, this compounds comprises: B-falls-3 beta-acetoxyl group-5s-hydroxyl-courage steroid-6-(4 '-phenyl) contracting ammonia sulphur hydrazone (1), B-falls-courage steroid-3 β, 5 beta-dihydroxyies-courage steroid-6-(4 '-phenyl) contracting ammonia sulphur hydrazone (2), B-fall-3 beta-acetoxyl group-5 beta-hydroxy-courage steroid-6-[4 '-(2 ' ', 4 ' '-dichlorophenyl)]-contracting ammonia sulphur hydrazone (3),-3 β fall in B-, 5 beta-dihydroxyies-courage steroid-6-[4 '-(2 ' ', 4 ' '-dichlorophenyl)] contracting ammonia sulphur hydrazone (4), B-falls-3 beta-acetoxyl group-5s-hydroxyl courage steroid-6-[4 '-(2 ' '-aminomethyl phenyl)] contracting ammonia sulphur hydrazone (5),-3 β fall in B-, 5 beta-dihydroxyl courage steroid-6-[4 '-(2 ' '-aminomethyl phenyl)] contracting ammonia sulphur hydrazone (6) steroidal compounds, the concrete structure formula is:
2. the described B-of claim 1 falls-preparation method of courage steroid-6-(4 '-phenyl class) contracting ammonia sulphur hydrazone steroidal compounds, it is characterized in that, and B-falls-and the preparation route of courage steroid-6-(4 '-phenyl class) contracting ammonia sulphur hydrazone steroidal compounds is as follows:
Annotate: 13%K
2CO
3Refer to that mass percent is 13% K
2CO
3The aqueous solution.
3. B-as claimed in claim 1 falls-3 beta-acetoxyl group-5s-hydroxyl-courage steroid-6-(4 '-phenyl) contracting ammonia sulphur hydrazone (1), B-falls-courage steroid-3 β, 5 beta-dihydroxyies-courage steroid-6-(4 '-phenyl) contracting ammonia sulphur hydrazone (2), B-fall-3 beta-acetoxyl group-5 beta-hydroxy-courage steroid-6-[4 '-(2 ' ', 4 ' '-dichlorophenyl)]-contracting ammonia sulphur hydrazone (3),-3 β fall in B-, 5 beta-dihydroxyies-courage steroid-6-[4 '-(2 ' ', 4 ' '-dichlorophenyl)] contracting ammonia sulphur hydrazone (4), B-falls-3 beta-acetoxyl group-5s-hydroxyl courage steroid-6-[4 '-(2 ' '-aminomethyl phenyl)] contracting ammonia sulphur hydrazone (5),-3 β fall in B-, 5 beta-dihydroxyl courage steroid-6-[4 '-(2 ' '-aminomethyl phenyl)] application of contracting ammonia sulphur hydrazone (6) steroidal compounds in the preparation antitumor drug.
With the described B-of claim 1 fall-courage steroid-6-(4 '-phenyl class) contracting ammonia sulphur hydrazone steroidal compounds is the application of medicinal compositions in the preparation antitumor drug of activeconstituents.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN105218614A (en) * | 2015-10-29 | 2016-01-06 | 广西师范学院 | 4-(4 '-bromine) phenyl-2-oestrone-17 '-hydrazone thiazole and its production and use |
| CN106866774A (en) * | 2016-12-23 | 2017-06-20 | 广西师范学院 | For antineoplastic compound and its production and use |
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| CN102146115A (en) * | 2011-01-17 | 2011-08-10 | 广西师范学院 | 3-substituent-B-Homo-steride-B-cyclolactam compound as well as preparation method and application to preparing antitumor medicaments |
| CN102286055A (en) * | 2011-06-29 | 2011-12-21 | 广西师范学院 | B-drop-3, 6-disubstituted cholestane compound and preparation method and application thereof to preparation of antitumor drug |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102146115A (en) * | 2011-01-17 | 2011-08-10 | 广西师范学院 | 3-substituent-B-Homo-steride-B-cyclolactam compound as well as preparation method and application to preparing antitumor medicaments |
| CN102286055A (en) * | 2011-06-29 | 2011-12-21 | 广西师范学院 | B-drop-3, 6-disubstituted cholestane compound and preparation method and application thereof to preparation of antitumor drug |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105218614A (en) * | 2015-10-29 | 2016-01-06 | 广西师范学院 | 4-(4 '-bromine) phenyl-2-oestrone-17 '-hydrazone thiazole and its production and use |
| CN106866774A (en) * | 2016-12-23 | 2017-06-20 | 广西师范学院 | For antineoplastic compound and its production and use |
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