CN105732755B - The aryl androstane 5 (6), 8 (14) of 3 β hydroxyls 16, the ketone of 15 (16) triolefin 17 - Google Patents
The aryl androstane 5 (6), 8 (14) of 3 β hydroxyls 16, the ketone of 15 (16) triolefin 17 Download PDFInfo
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- CN105732755B CN105732755B CN201610093315.4A CN201610093315A CN105732755B CN 105732755 B CN105732755 B CN 105732755B CN 201610093315 A CN201610093315 A CN 201610093315A CN 105732755 B CN105732755 B CN 105732755B
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- ketone
- triolefin
- androstane
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- 125000002887 hydroxy group Chemical group [H]O* 0.000 title abstract description 10
- 150000002576 ketones Chemical class 0.000 title abstract description 5
- -1 aryl androstane Chemical compound 0.000 title abstract description 3
- 150000001875 compounds Chemical class 0.000 abstract description 26
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 40
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 23
- 210000004027 cell Anatomy 0.000 description 20
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 16
- 238000005160 1H NMR spectroscopy Methods 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- 150000003431 steroids Chemical class 0.000 description 11
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 10
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 238000004440 column chromatography Methods 0.000 description 10
- 238000001035 drying Methods 0.000 description 10
- 239000012074 organic phase Substances 0.000 description 10
- 230000003637 steroidlike Effects 0.000 description 10
- 238000003786 synthesis reaction Methods 0.000 description 10
- QZLYKIGBANMMBK-UGCZWRCOSA-N 5α-Androstane Chemical compound C([C@@H]1CC2)CCC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CCC[C@@]2(C)CC1 QZLYKIGBANMMBK-UGCZWRCOSA-N 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 9
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 9
- 239000002994 raw material Substances 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 229910000029 sodium carbonate Inorganic materials 0.000 description 8
- 239000012265 solid product Substances 0.000 description 8
- 238000010792 warming Methods 0.000 description 8
- 238000005406 washing Methods 0.000 description 6
- 206010028980 Neoplasm Diseases 0.000 description 5
- 201000011510 cancer Diseases 0.000 description 5
- 239000013078 crystal Substances 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
- 206010006187 Breast cancer Diseases 0.000 description 4
- 208000026310 Breast neoplasm Diseases 0.000 description 4
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 4
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 4
- 235000010338 boric acid Nutrition 0.000 description 4
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- ICIWUVCWSCSTAQ-UHFFFAOYSA-M iodate Chemical compound [O-]I(=O)=O ICIWUVCWSCSTAQ-UHFFFAOYSA-M 0.000 description 4
- 201000005296 lung carcinoma Diseases 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N CHCl3 Substances ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 3
- 230000001093 anti-cancer Effects 0.000 description 3
- 201000008275 breast carcinoma Diseases 0.000 description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
- 206010017758 gastric cancer Diseases 0.000 description 3
- 208000010749 gastric carcinoma Diseases 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 230000002611 ovarian Effects 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 201000000498 stomach carcinoma Diseases 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- SHAHPWSYJFYMRX-GDLCADMTSA-N (2S)-2-(4-{[(1R,2S)-2-hydroxycyclopentyl]methyl}phenyl)propanoic acid Chemical compound C1=CC([C@@H](C(O)=O)C)=CC=C1C[C@@H]1[C@@H](O)CCC1 SHAHPWSYJFYMRX-GDLCADMTSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 0 Cc1cc(*)ccc1 Chemical compound Cc1cc(*)ccc1 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- TZYWCYJVHRLUCT-VABKMULXSA-N N-benzyloxycarbonyl-L-leucyl-L-leucyl-L-leucinal Chemical compound CC(C)C[C@@H](C=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)OCC1=CC=CC=C1 TZYWCYJVHRLUCT-VABKMULXSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- GZOSMCIZMLWJML-VJLLXTKPSA-N abiraterone Chemical compound C([C@H]1[C@H]2[C@@H]([C@]3(CC[C@H](O)CC3=CC2)C)CC[C@@]11C)C=C1C1=CC=CN=C1 GZOSMCIZMLWJML-VJLLXTKPSA-N 0.000 description 2
- 229960000853 abiraterone Drugs 0.000 description 2
- 150000001336 alkenes Chemical class 0.000 description 2
- 125000003342 alkenyl group Chemical group 0.000 description 2
- 239000004327 boric acid Substances 0.000 description 2
- 125000005619 boric acid group Chemical class 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- UQPXMPFYIZSCND-IHMRHOJGSA-N (5R,8R,9S,10S,13R,14S)-15-iodo-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene Chemical class IC1[C@@H]2[C@](CC1)(C)CC[C@H]1[C@H]2CC[C@H]2CCCC[C@]12C UQPXMPFYIZSCND-IHMRHOJGSA-N 0.000 description 1
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 1
- QFMZQPDHXULLKC-UHFFFAOYSA-N 1,2-bis(diphenylphosphino)ethane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCP(C=1C=CC=CC=1)C1=CC=CC=C1 QFMZQPDHXULLKC-UHFFFAOYSA-N 0.000 description 1
- MEKOFIRRDATTAG-UHFFFAOYSA-N 2,2,5,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound C1CC(C)(C)OC2=C1C(C)=C(O)C=C2C MEKOFIRRDATTAG-UHFFFAOYSA-N 0.000 description 1
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 1
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 1
- OVDGUTHABMXVMI-UHFFFAOYSA-N 3-nitro-4-(propylamino)benzoic acid Chemical compound CCCNC1=CC=C(C(O)=O)C=C1[N+]([O-])=O OVDGUTHABMXVMI-UHFFFAOYSA-N 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- WNIKHQHQFRFBSD-SMRYLSCZSA-N CC(C)C(C)/C=C/C(/C)=C(/[C@@H](C1)OC(C(C2O)O)OC(CO)C2O)\[C@]2(C)C1=C1C=C[C@@H](CC(CC3)=O)C3(C)C1CC2 Chemical compound CC(C)C(C)/C=C/C(/C)=C(/[C@@H](C1)OC(C(C2O)O)OC(CO)C2O)\[C@]2(C)C1=C1C=C[C@@H](CC(CC3)=O)C3(C)C1CC2 WNIKHQHQFRFBSD-SMRYLSCZSA-N 0.000 description 1
- SBPQVIDAOKLTIS-HQHDJMJFSA-N CC(C)C(C)/C=C/C(/C)=C(/[C@@H](C1)OC(C(C2O)O)OC(CO)C2O)\[C@]2(C)C1=C1C=C[C@@H](C[C@H](CC3)O)[C@@]3(C)C1CC2 Chemical compound CC(C)C(C)/C=C/C(/C)=C(/[C@@H](C1)OC(C(C2O)O)OC(CO)C2O)\[C@]2(C)C1=C1C=C[C@@H](C[C@H](CC3)O)[C@@]3(C)C1CC2 SBPQVIDAOKLTIS-HQHDJMJFSA-N 0.000 description 1
- 241000778168 Callyspongia Species 0.000 description 1
- BURBKNLNSIZIFI-UHFFFAOYSA-N Cc1c-2nc-2nc1 Chemical compound Cc1c-2nc-2nc1 BURBKNLNSIZIFI-UHFFFAOYSA-N 0.000 description 1
- VLPWXHZDGMUMBR-UHFFFAOYSA-N Cc1cc(OC)cnc1 Chemical compound Cc1cc(OC)cnc1 VLPWXHZDGMUMBR-UHFFFAOYSA-N 0.000 description 1
- BTQZKHUEUDPRST-UHFFFAOYSA-N Cc1cccc(F)c1 Chemical compound Cc1cccc(F)c1 BTQZKHUEUDPRST-UHFFFAOYSA-N 0.000 description 1
- MMZYCBHLNZVROM-UHFFFAOYSA-N Cc1ccccc1F Chemical compound Cc1ccccc1F MMZYCBHLNZVROM-UHFFFAOYSA-N 0.000 description 1
- ITQTTZVARXURQS-UHFFFAOYSA-N Cc1cccnc1 Chemical compound Cc1cccnc1 ITQTTZVARXURQS-UHFFFAOYSA-N 0.000 description 1
- 241000157663 Chadsia flammea Species 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- QGXBDMJGAMFCBF-UHFFFAOYSA-N Etiocholanolone Natural products C1C(O)CCC2(C)C3CCC(C)(C(CC4)=O)C4C3CCC21 QGXBDMJGAMFCBF-UHFFFAOYSA-N 0.000 description 1
- 206010022998 Irritability Diseases 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- UFXXGUUBTPZQIL-UHFFFAOYSA-N OBO.FC(F)(F)C1=CC=CC=C1 Chemical class OBO.FC(F)(F)C1=CC=CC=C1 UFXXGUUBTPZQIL-UHFFFAOYSA-N 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 229910002666 PdCl2 Inorganic materials 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 206010037742 Rabies Diseases 0.000 description 1
- 206010039966 Senile dementia Diseases 0.000 description 1
- OHLYNNCKSRHVQV-UHFFFAOYSA-N [AlH]=Cc1ccccc1 Chemical compound [AlH]=Cc1ccccc1 OHLYNNCKSRHVQV-UHFFFAOYSA-N 0.000 description 1
- 229960004103 abiraterone acetate Drugs 0.000 description 1
- 239000000370 acceptor Substances 0.000 description 1
- 210000004100 adrenal gland Anatomy 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000003098 androgen Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- VZGDMQKNWNREIO-UHFFFAOYSA-N carbon tetrachloride Substances ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 239000002254 cytotoxic agent Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- QGXBDMJGAMFCBF-LUJOEAJASA-N epiandrosterone Chemical compound C1[C@@H](O)CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC[C@H]21 QGXBDMJGAMFCBF-LUJOEAJASA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 description 1
- 229910052808 lithium carbonate Inorganic materials 0.000 description 1
- IPLONMMJNGTUAI-UHFFFAOYSA-M lithium;bromide;hydrate Chemical compound [Li+].O.[Br-] IPLONMMJNGTUAI-UHFFFAOYSA-M 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000010813 municipal solid waste Substances 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- JKDRQYIYVJVOPF-FDGPNNRMSA-L palladium(ii) acetylacetonate Chemical compound [Pd+2].C\C([O-])=C\C(C)=O.C\C([O-])=C\C(C)=O JKDRQYIYVJVOPF-FDGPNNRMSA-L 0.000 description 1
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 150000004291 polyenes Chemical class 0.000 description 1
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- RDRCCJPEJDWSRJ-UHFFFAOYSA-N pyridine;1h-pyrrole Chemical compound C=1C=CNC=1.C1=CC=NC=C1 RDRCCJPEJDWSRJ-UHFFFAOYSA-N 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000005504 styryl group Chemical group 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
- C07J1/0003—Androstane derivatives
- C07J1/0011—Androstane derivatives substituted in position 17 by a keto group
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J43/00—Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton
- C07J43/003—Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton not condensed
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Steroid Compounds (AREA)
Abstract
The present invention relates to a kind of compound, including：The aryl androstane 5 (6), 8 (14) of 3 β hydroxyls 16, the ketone of 15 (16) triolefin 17, its structural formula is as follows：Wherein, Ar is selected from the one kind in having structure：Its compound has following 8：
Description
Technical field
The invention belongs to the field of chemical synthesis, it is related to 3 beta-hydroxy -16- aryl androstanes -5 (6), 8 (14), 15 (16)-three
Alkene -17- ketone, 8 compounds of (16)-triolefin -17- ketone of specifically 3 beta-hydroxy -16- aryl androstane -5 (6), 8 (14), 15.
Background technology
The transformation and modification of natural steroid are increasingly paid close attention to by people, by some specific modifications, such as steroid
The modification of body ring, side chain, can obtain some important better than parent bioactive steroid derivatives【Levina,
I.S.；Pokrovskaya,E.V.；Kulikova,L.E.；Kamernitzky,A.V.；Kachala,V.V.；Smirnov,
A.N.Steroids.2008,73,815】.Such as have been used to the Abiraterone acetate ester (abiraterone of clinic
Acetate), chemical entitled 17- (3- pyridine radicals) androstane -5, -3 β of 16- diene-acetic acid esters are public by Centocor Ortho
The enzyme irreversible inhibitors of orally active CYP 17 of exploitation are taken charge of, by changing into abiraterone to testis and other body parts
Such as the androgen of adrenal gland generation plays inhibitory action.The approval listing of the Nikkei U.S. FDA of April 28 in 2011, is combined with metacortandracin
Treatment prostate cancer【G.A.Potter,S.E.Barrie,M.Jarman and M.G.Rowlands,J.Med.Chem.,
1995,38,2463.】.
Many researchs find, when steroidal D rings are modified, if it is possible to retain the carbonyl of steroidal C-17, and in the neighbour of carbonyl
Some characteristic side chains are introduced on position C-16, the physiological function better than parent compound is equally obtained in that
【Chattopadhaya,R.；Jindal,D.P.；Minu,M.；Gupta,R.Arzneim.Forsch.2004,54,551；
Bansal,R.；Guleria,S.Steroids.2008,73,1391；Dubey,S.；Kaur,P.；Jindal,D.P.；
Satyanarayan,Y.D.；Piplani,P.Med.Chem.2008,4,229；Guo,H.；Wu,H.；Yang,J.；Xiao,Y.；
Altenbach,H.；Qiu,G.；Hu,H.；Wu,Z.；He,X.；Zhou,D.；Hu,X.Steroids.2011,76,709；
Moreira,V.M.；Salvador,J.A.R.；Bejad,A.M.；Paixaod,J.A.Steroids.2011,76,582.】.Such as
2004, Dubey et al. synthesized a series of 16- (styryl that 4- replaces)-androstane -5- ene derivatives by multistep, carefully
Cytoactive test shows that this is the new cytotoxic drug of a class, by three kinds of cancer cells to human body：Breast cancer cell
The anticancer experiment in vitro of MCF-7, lung carcinoma cell NCI-H460 and central nerve tumor cell SF-268 these three human cancer cells,
It was found that these compounds can induce the cancer cell-apoptosis of human body, so as to suppress the propagation of tumour cell【Dubey,S.；
Piplani,P.；Jindal,D.P.Chem Biodiver.2004,1,1529.】.2007, Gamal seminars reported
Epiandrosterone D- environmental protection has been bonded a heterocycle structure in the case of staying 17- carbonyl, obtain good antibacterial activity
【Mervat,M.；Abdelhalim.；Manal,M.T.；Samira,T.；Rabie.；Gamal,A.Steroids.2007,72,
459.】.2012, Bansa et al. on the carbon atom of 16 of steroidal D rings, was retaining with androstane dehydroepiandros-sterone as raw material
An imidazole radicals is bonded on the basis of 17- carbonyl, biological activity test shows the work with very strong suppression cancer cell
With【Ranju,B.；Sheetal,G.；Sridhar,T.；Subhash,L.；Patwar,R.Steroids.2012,77,621.】.
Recently research finds such as there are multiple alkenyls in steroidal ring, can more strengthen the physiologically active of steroidal compounds.Such as
Gabriele M. in 2015Et al. three polyene-based steroids are separated to from sponge Callyspongia cf.C.flammea
Body compound, especially it is worth noting that there is C (8)=C that general steroid derivative is not commonly formed in these steroidal compounds
(14) alkenyl.There is these compounds suppression Aftin-5 cells to produce Ab-42 and be used to treat senile dementia.
The content of the invention
For the above defect, the invention provides 3 beta-hydroxy -16- aryl androstanes -5 (6), 8 (14), 15 (16)-three
Alkene -17- ketone, structural formula is as follows：
Wherein, Ar- is selected from the one kind in having structure：
Its compound has following 8：
C3 is 3 beta-hydroxies in structural formula of the present invention；It is double bond between C8 and C14；It is double bond between C5 and C6；C15 and C16
Between be double bond.
Except remaining the due active structure of steroidal in the present invention, while 17- carbonyl of reservation on steroidal D rings,
α is built in steroidal rigid backbone, beta-unsaturated carbonyl construction unit can be combined with various acceptors, show extensive biology
Activity.
Further, (16)-triolefin -17- ketone of 3 beta-hydroxy -16- aryl androstane -5 (6), 8 (14), 15 is in active anticancer
Using.
Before (16)-triolefin -17- ketone of 3 beta-hydroxy -16- aryl androstane -5 (6), 8 (14), 15 of the invention can be as medicine
Body, used as clinical medicine screening compounds, further research can be pharmaceutically acceptable with one or more pharmaceutic adjuvant academic title
Any formulation.
Specific embodiment
(16)-triolefin -17- ketone of 3 beta-hydroxy -16- aryl androstane -5 (6), 8 (14), 15 of the invention, its structural formula is as follows：
Wherein, Ar- is selected from the one kind in having structure：
Its compound has following 8：
C3 is 3 beta-hydroxies in structural formula of the present invention；It is double bond between C8 and C14；It is double bond between C5 and C6；C15 and C16
Between be double bond.
Tester
Infrared spectrum analysis：The infrared spectrometers of Bruker tensor 27, KBr pressed disc methods, detection range be 4000~
400cm-1；Fusing point is measured：WRR melting point apparatus (Shanghai Precision Scientific Apparatus Co., Ltd), data are not calibrated.1H-NMR and13C-
NMR is analyzed：Bruker Advance 600 (German Bruker companies)；Reaction process TLC tracing detections.
Embodiment 1：Key intermediate (3 β)-hydroxy-androst -5 (6), the conjunction of 8 (14), 15 (16)-triolefin -17- ketone (3)
Into
Take compound (6) 3.67g (0.01mol), water lithium bromide 3.67g (0.035mol), lithium carbonate 2.96g
(0.04mol), 30mL DMF, backflow, nitrogen protection.Stop reaction after 8h, be added dropwise in trash ice after cooling, stir, there is solid
Body is separated out, and suction filtration obtains yellow solid.Dissolved with DCM, washed with water successively, saturated common salt is washed 1-2 times, is then collected organic
Phase, anhydrous sodium sulfate drying is spin-dried for obtaining yellow, viscous solid, column chromatography, DCM:EA=20:1, collect second point and obtain
0.88g, yield 31.0%；IR(KBr,cm-1):3312,2930,2858,1709,1643,1519,1453,1219,1108,
1009,940,865,700；13C-NMR(150MHz,CDCl3)δ(ppm):212.2,152.69,141.65,139.34,
133.78,128.06,118.87,70.98,48.28,45.75,41.59,38.87,36.34,31.50,28.97,27.63,
22.95,19.50,18.82；Mp:194-195℃；1H NMR(600MHz,CDCl3)δ(ppm):7.81 (d, J=5.7Hz, 1H),
5.94 (d, J=5.7Hz, 1H), 5.28 (s, 1H), 3.52 (m, 1H), 1.12 (s, 3H), 0.95 (s, 3H)；MS(EI)(m/z):
285.43[(M+1)+] (100%)
Embodiment 2：The iodo- androstanes -5 of (3 β)-hydroxyl -16- (6), the synthesis of 8 (14), 15 (16)-triolefin -17- ketone (4)
Take compound (7) 0.50g (1.74mmol), iodine 0.89g (3.48mmol), DMAP 0.01g (0.087mmol), pyrrole
Pyridine 6mL (0.07mmol), CCl415mL is stirred overnight in being stirred at 0 DEG C.After reaction is spin-dried for solvent after terminating, extracted with DCM
Afterwards, washed 1-2 times with the solution of the sodium thiosulfate of saturation, 20% watery hydrochloric acid washes 1-2 after, and saturated common salt is washed one time,
Collect organic phase, anhydrous sodium sulfate drying.Column chromatography, DCM:EA=20:1, obtain light brown product, yield 80%.1H-NMR
(600MHz,CDCl3)δ(ppm):8.16(s,1H),5.28(s,1H),3.68-3.39(m,1H),1.15(s,3H),0.94(s,
3H)；13C-NMR(150MHz,CDCl3)δ(ppm):204.62,158.00,140.59,138.94,133.13,117.62,
97.47,69.95,47.06,43.82,40.52,37.88,35.24,30.46,28.06,26.81,22.11,18.52,
17.70.IR(KBr):3468,2929,2858,1700,1657,1513,1450,1370,1276,1211,1062,1004,
937,918,846,734；HRMS(ESI)calcd for C19H23IO2[M+H]412.0822；Found 411.0818；Mp:
135-136℃(PE/AcOEt).
Embodiment 3：The synthesis of (16)-triolefin -17- ketone (5a) of (3 β)-hydroxyl -16- phenyl androstane -5 (6), 8 (14), 15
Take compound (3 the β)-iodo- androstanes -5 of hydroxyl -16- (6), 8 (14), 15 (16)-triolefin -17- ketone 0.50g
(1.2mmol), phenyl boric acid 0.26g (2.13mmol), bis-triphenylphosphipalladium palladium dichloride 0.017g (0.024mmol), cuprous iodide
0.0024g (0.013mmol), THF20mL, methyl alcohol 4mL, are subsequently added 2M sodium carbonate liquor 2.4mL, are warming up to backflow.After 10h
Consumption of raw materials is finished.Reaction terminates, and after being spin-dried for solvent, is extracted with DCM, afterwards, washes with water 1-2 times, saturated common salt washing 1-2
Time, collect organic phase, anhydrous sodium sulfate drying.Column chromatography, DCM:EA=10:1, obtain faint yellow solid product, yield：
91%.Mp:175-176℃(PE/AcOEt)；1H-NMR(600MHz,CDCl3)δ(ppm):7.96 (s, 1H), 7.77 (d, J=
7.7Hz, 2H), 7.31 (t, J=7.6Hz, 2H), 7.24 (t, J=7.3Hz, 1H), 5.31 (s, 1H), 3.53 (m, 1H), 1.19
(s,3H),0.96(s,3H)；13C-NMR(150MHz,CDCl3)δ(ppm):209.53,146.57,141.62,137.77,
136.78,133.70,132.22,128.49,128.29,127.12,119.04,71.05,48.53,47.50,41.61,
38.98,36.33,31.52,29.11,27.87,23.36,19.58,18.87；IR(KBr,cm-1):3462,2929,2856,
1684,1450,1339,1292,1176,1059,927,795,750,654；HRMS(ESI)calcd for C25H28O2[M+H]
361.2168；Found 361.2164.
Pd catalyst optional Pd (dppf) Cl2, Pd (PPh3)4,Pd(acac)2,PdCl2(DPPE), Pd/C or Pd (CH3CN)
Cl2。
Embodiment 4：(3 β)-hydroxyl -16- (3- pyridine radicals) androstane -5 (6), 8 (14), 15 (16)-triolefin -17- ketone (5b)
Synthesis
Take compound (3 the β)-iodo- androstanes -5 of hydroxyl -16- (6), 8 (14), 15 (16)-triolefin -17- ketone 0.50g
(1.2mmol), pyridine -3- boric acid 0.26g (2.13mmol), bis-triphenylphosphipalladium palladium dichloride 0.017g (0.024mmol), iodate
Cuprous 0.0024g (0.013mmol), THF20mL, methyl alcohol 4mL are subsequently added 2M sodium carbonate liquor 2.4mL, are warming up to backflow.
Consumption of raw materials is finished after 10h.Reaction terminates, and after being spin-dried for solvent, is extracted with DCM, afterwards, washes with water 1-2 times, saturated common salt washing
1-2 times, collect organic phase, anhydrous sodium sulfate drying.Column chromatography, DCM:EA=10:1, obtain faint yellow solid product, yield:
85%, Mp:167-168℃(PE/AcOEt)；1H-NMR(600MHz,CDCl3)δ(ppm):8.91 (s, 1H), 8.46 (d, J=
4.4Hz, 1H), 8.17 (d, J=7.9Hz, 1H), 8.06 (s, 1H), 7.28-7.23 (m, 1H), 5.32 (s, 1H), 3.58-3.51
(m,1H),1.98(s,1H),1.20(s,3H),0.98(s,3H)；13C-NMR(150MHz,CDCl3)δ(ppm):208.10,
147.92,147.00,146.13,140.75,136.75,134.59,133.43,132.83,122.32,119.83,117.80,
69.99,47.61,46.25,40.57,38.05,35.31,30.49,29.90,26.80,22.26,18.57,17.80；IR
(KBr,cm-1):3472,2928,2857,1697,1647,1458,1415,1376,1299,1066,933,808；HRMS(ESI)
calcd forC24H27NO2[M+H]362.2121；Found 362.2112.
Embodiment 5：(3 β)-hydroxyl -16- (2- fluorophenyls) androstane -5 (6), 8 (14), 15 (16)-triolefin -17- ketone (5c)
Synthesis
Take compound (3 the β)-iodo- androstanes -5 of hydroxyl -16- (6), 8 (14), 15 (16)-triolefin -17- ketone 0.50g
(1.2mmol), 2- fluorobenzoic boric acids 0.30g (2.13mmol), bis-triphenylphosphipalladium palladium dichloride 0.017g (0.024mmol), iodate
Cuprous 0.0024g (0.013mmol), THF20mL, methyl alcohol 4mL are subsequently added 2M sodium carbonate liquor 2.4mL, are warming up to backflow.
Consumption of raw materials is finished after 10h.Reaction terminates, and after being spin-dried for solvent, is extracted with DCM, afterwards, washes with water 1-2 times, saturated common salt washing
1-2 times, collect organic phase, anhydrous sodium sulfate drying.Column chromatography, DCM:EA=10:1, obtain faint yellow solid product, yield:
86%, Mp:164-165℃(PE/AcOEt)；1H-NMR(600MHz,CDCl3)δ(ppm):8.17 (s, 1H), 8.01 (t, J=
7.2Hz, 1H), 7.22-7.17 (m, 2H), 7.10 (dd, J=13.5,6.1Hz, 1H), 5.31 (s, 1H), 3.53 (m, 1H),
1.20(s,3H),0.97(s,3H)；13C-NMR(150MHz,CDCl3)δ(ppm):(d, J=249.6Hz), 209.43,159.53
149.42 (d, J=10.2Hz), 140.49,137.02,133.70,130.16,129.91,128.32 (d, J=8.5Hz),
123.03 (d, J=3.3Hz), 119.13 (d, J=12.3Hz), 118.02,114.62 (d, J=22.3Hz), 70.02,
47.58,45.45,40.58,37.98,35.32,30.49,28.05,26.82,22.31,18.54,17.84；IR(KBr,cm-1):3491,3043,2930,2859,1691,1562,1480,1449,1274,1213,1110,1055,930,875,800,
758,722；HRMS(ESI)calcd for C25H27FO2[M+H]379.2074；Found 379.2074.
Embodiment 6：(3 β)-hydroxyl -16- (3- fluorophenyls) androstane -5 (6), 8 (14), 15 (16)-triolefin -17- ketone (5d)
Synthesis
Take compound (3 the β)-iodo- androstanes -5 of hydroxyl -16- (6), 8 (14), 15 (16)-triolefin -17- ketone 0.50g
(1.2mmol), 3- fluorobenzoic boric acids 0.30g (2.13mmol), bis-triphenylphosphipalladium palladium dichloride 0.017g (0.024mmol), iodate
Cuprous 0.0024g (0.013mmol), THF20mL, methyl alcohol 4mL are subsequently added 2M sodium carbonate liquor 2.4mL, are warming up to backflow.
Consumption of raw materials is finished after 10h.Reaction terminates, and after being spin-dried for solvent, is extracted with DCM, afterwards, washes with water 1-2 times, saturated common salt washing
1-2 times, collect organic phase, anhydrous sodium sulfate drying.Column chromatography, DCM:EA=10:1, obtain faint yellow solid product, yield:
84%, Mp:190-191℃(PE/AcOEt)；1H-NMR(600MHz,CDCl3)δ(ppm):7.97 (s, 1H), 7.55 (t, J=
7.7Hz, 2H), 7.27 (dd, J=14.3,7.8Hz, 1H), 6.93 (t, J=7.6Hz, 1H), 5.32 (s, 1H), 3.53 (m,
1H),1.19(s,3H),0.97(s,3H)；13C-NMR(150MHz,CDCl3)δ(ppm):207.90,161.88 (d, J=
245.6Hz), 146.03,140.69,136.62,134.57 (d, J=2.1Hz), 133.75,133.32,128.89 (d, J=
8.1Hz), 121.69 (d, J=2.8Hz), 117.90,114.04 (d, J=21.3Hz), 112.96 (d, J=22.8Hz),
70.05,47.64,46.57,40.63,38.02,35.35,30.56,28.13,26.88,22.32,18.56,17.84；IR
(KBr,cm-1):3500,3075,2928,2857,1679,1577,1426,1340,1263,1185,1058,886,790,681；
HRMS(ESI)calcd for C25H27FO2[M+H]379.2074；Found 379.2074.
Embodiment 7：(3 β)-hydroxyl -16- (4- fluoro-3-pyridines) androstane -5 (6), 8 (14), 15 (16)-triolefin -17- ketone
The synthesis of (5e)
Take compound (3 the β)-iodo- androstanes -5 of hydroxyl -16- (6), 8 (14), 15 (16)-triolefin -17- ketone 0.50g
(1.2mmol), 4- fluoro-3-pyridine boric acid 0.30g (2.13mmol), bis-triphenylphosphipalladium palladium dichloride 0.017g (0.024mmol),
Cuprous iodide 0.0024g (0.013mmol), THF20mL, methyl alcohol 4mL, are subsequently added 2M sodium carbonate liquor 2.4mL, are warming up to back
Stream.Consumption of raw materials is finished after 10h.Reaction terminates, and after being spin-dried for solvent, is extracted with DCM, afterwards, washes with water 1-2 times, saturated common salt
Washing 1-2 times, collects organic phase, anhydrous sodium sulfate drying.Column chromatography, DCM:EA=10:1, faint yellow solid product is obtained, produce
Rate:90%, Mp:180-181℃(PE/AcOEt)；1H-NMR(600MHz,CDCl3)δ(ppm):8.56(s,1H),8.26(t,J
=7.2Hz, 1H), 8.02 (s, 1H), 6.89 (d, J=6.6Hz, 1H), 5.32 (s, 1H), 3.54 (m, 1H), 1.20 (s, 3H),
0.98(s,3H)；13C-NMR(150MHz,CDCl3)δ(ppm):(d, J=238.5Hz), 207.92,162.11 145.84,
145.04 (d, J=14.7Hz), 140.67,138.64 (d, J=8.0Hz), 136.54,134.65,131.76 (d, J=
2.9Hz), 125.34,117.74,108.24 (d, J=37.3Hz), 70.00,47.61,46.19,40.57,38.05,35.31,
30.49,28.17,26.78,22.25,18.56,17.79；IR(KBr,cm-1):3497,2696,2930,2851,2818,
1680,1587,1472,1376,1297,1176,1120,1069,1022,928,834,744,670；HRMS(ESI)calcd
for C24H26FNO2[M+H]380.2027；Found 380.2012.
Embodiment 8：(3 β)-hydroxyl -16- (5- pyrimidines) androstane -5 (6), 8 (14), 15 (16)-triolefin -17-'s ketone (5f)
Synthesis
Take compound (3 the β)-iodo- androstanes -5 of hydroxyl -16- (6), 8 (14), 15 (16)-triolefin -17- ketone 0.50g
(1.2mmol), 5- pyrimidine boronic acids 0.26g (2.13mmol), bis-triphenylphosphipalladium palladium dichloride 0.017g (0.024mmol), iodate
Cuprous 0.0024g (0.013mmol), THF20mL, methyl alcohol 4mL are subsequently added 2M sodium carbonate liquor 2.4mL, are warming up to backflow.
Consumption of raw materials is finished after 10h.Reaction terminates, and after being spin-dried for solvent, is extracted with DCM, afterwards, washes with water 1-2 times, saturated common salt washing
1-2 times, collect organic phase, anhydrous sodium sulfate drying.Column chromatography, DCM:EA=10:1, obtain faint yellow solid product, yield:
87%, Mp:203-204℃(PE/AcOEt)；1H-NMR(600MHz,CDCl3)δ(ppm):9.11(s,2H),9.07(s,1H),
8.13(s,1H),5.32(s,1H),3.59–3.50(m,1H),1.21(s,3H),0.98(s,3H)；13C-NMR(150MHz,
CDCl3)δ(ppm):207.56,156.63,153.76,146.98,140.77,136.67,136.43,129.91,125.53,
117.52,69.89,47.69,46.10,40.54,38.16,35.32,30.46,28.26,26.73,22.19,18.60,
17.75；IR(KBr,cm-1):3487,3034,2940,2861,2799,1701,1644,1558,1406,1299,1144,
1009,932,721；HRMS(ESI)calcd for C23H26N2O2[M+H]363.2073；Found 363.2068.
Embodiment 9：(3 β)-hydroxyl -16- (3- trifluoromethyls) androstane -5 (6), 8 (14), 15 (16)-triolefin -17-
The synthesis of ketone (5g)
Take compound (3 the β)-iodo- androstanes -5 of hydroxyl -16- (6), 8 (14), 15 (16)-triolefin -17- ketone 0.50g
(1.2mmol), 3- trifluoromethylbenzene boronic acids 0.40g (2.13mmol), bis-triphenylphosphipalladium palladium dichloride 0.017g
(0.024mmol), cuprous iodide 0.0024g (0.013mmol), THF20mL, methyl alcohol 4mL, is subsequently added 2M sodium carbonate liquors
2.4mL, is warming up to backflow.Consumption of raw materials is finished after 10h.Reaction terminates, and after being spin-dried for solvent, is extracted with DCM, afterwards, washes with water
1-2 times, saturated common salt is washed 1-2 times, collects organic phase, anhydrous sodium sulfate drying.Column chromatography, DCM:EA=10:1, obtain light
Yellow solid product, yield:93%, Mp:195-196℃(PE/AcOEt)；1H-NMR(600MHz,CDCl3)δ(ppm):8.04
(s, 1H), 8.02 (s, 1H), 7.99 (d, J=7.8Hz, 1H), 7.49 (d, J=7.7Hz, 1H), 7.43 (t, J=7.8Hz,
1H),5.32(s,1H),3.56-3.52(m,1H),1.20(s,3H),0.98(s,3H)；13C-NMR(150MHz,CDCl3)δ
(ppm):(d, J=8.5Hz), 207.94,146.41,140.64,136.56,134.31 131.99,129.87 (q, J=
32.6Hz), 129.28,127.91,123.98,123.69 (q, J=3.7Hz), 123.07 (q, J=271.5Hz), 122.74
(q, J=3.5Hz), 117.83,70.02,47.63,46.50,40.58,38.03,35.31,30.50,28.17,2 6.82,
22.28,18.56,17.81；IR(KBr,cm-1):3489,3032,2939,2894,2827,1680,1587,1475,1419,
1322,1123,1006,805；HRMS(ESI)calcd for C26H27F3O2[M+H]429.2042；Found 429.2039.
Embodiment 10：(3 β)-hydroxyl -16- (5- methoxyl group -3- pyridines) androstane -5 (6), 8 (14), 15 (16)-triolefins -
The synthesis of 17- ketone (5h)
Take compound (3 the β)-iodo- androstanes -5 of hydroxyl -16- (6), 8 (14), 15 (16)-triolefin -17- ketone 0.50g
(1.2mmol), 5- methoxypyridines -3- boric acid 0.36g (2.13mmol), bis-triphenylphosphipalladium palladium dichloride 0.017g
(0.024mmol), cuprous iodide 0.0024g (0.013mmol), THF20mL, methyl alcohol 4mL, is subsequently added 2M sodium carbonate liquors
2.4mL, is warming up to backflow.Consumption of raw materials is finished after 10h.Reaction terminates, and after being spin-dried for solvent, is extracted with DCM, afterwards, washes with water
1-2 times, saturated common salt is washed 1-2 times, collects organic phase, anhydrous sodium sulfate drying.Column chromatography, DCM:EA=10:1, obtain depth
Yellow solid product, yield:74%, Mp:193-194℃(PE/AcOEt)；1H-NMR(600MHz,CDCl3)δ(ppm):8.49
(s,1H),8.16(s,1H),8.07(s,1H),7.79(s,1H),5.32(s,1H),3.82(s,3H),3.57-3.50(m,
1H),1.20(s,3H),0.97(s,3H)；13C-NMR(150MHz,CDCl3)δ(ppm):208.27,154.50,146.50,
140.67,139.05,136.60,136.17,134.84,132.37,127.83,117.76,117.45,69.95,54.57,
47.64,46.32,40.57,38.07,35.32,30.48,28.19,26.80,22.26,18.57,17.80；IR(KBr,cm-1):3488,2930,2872,1686,1610,1521,1450,1370,1296,1119,1008,940；HRMS(ESI)calcd
for C25H29NO3[M+H]392.2226；Found 392.2229.
From CH2Cl2The crystal of 5a is obtained in solvent and from CHCl3The crystal of 5b is obtained in solvent, is spread out by X-ray monocrystalline
Capable sign is injected, crystal data information is listed in Table 2 below.Crystal structure further demonstrates the structure of target compound, and can
To find out the presence of the double bond on the position of steroidal 8 (14).
The molecular structure of compound 5a (contains CH2Cl2)
The molecular structure of compound 5b (contains CHCl3)
The crystal parameter of table 1 compound 5a and 5b
Embodiment 11：The test of active anticancer
Synthesized compound 5a-h to A549 human lung carcinoma cells, SKOV3 Proliferation of Human Ovarian Cell, MKN45 gastric carcinoma cells and
The inhibitory action of MDA-MB-435 human breast carcinoma high-transfer cell in-vitro multiplications is tested.
Test result shows synthesized compound 5a-h to A549 human lung carcinoma cells, SKOV3 Proliferation of Human Ovarian Cell, MKN45
Gastric carcinoma cells and MDA-MB-435 human breast carcinoma high-transfer cells etc. are all inhibited, and all compounds are to SKOV3 people
Ovarian cancer cell inhibitory action is better than to other three class human cancer cells.And there is the compound 5c, 5d, 5e of fluoro substituents on aryl
It is best with 5g inhibitions.
Inhibitory action (half-inhibition concentration) of the compound 5a-h of table 2 to man―machine systems in-vitro multiplicationa
aExperimental result takes eight experimental data average value ± standard deviations
bA549:Human lung carcinoma cell, SKOV3:Proliferation of Human Ovarian Cell, MKN-45:Gastric carcinoma cells,
MDA-MB-435:Human breast carcinoma high-transfer cell.
Claims (1)
- (16)-triolefin -17- ketone of 1.3 beta-hydroxy -16- aryl androstane -5 (6), 8 (14), 15, it is characterised in that its structural formula is such as Under：Wherein, Ar- is selected from the one kind in having structure。
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| CN103073607A (en) * | 2013-02-26 | 2013-05-01 | 昆明理工大学 | 12[beta]-hydroxyandrostane-4,6,8(9),13(14)-tetraene-3,11,16-triketone and application thereof |
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