BG62972B1 - 7 алфа-(ипсилон-аминоалкил)-естратрини, метод за получаването им, фармацевтични препарати съдържащитези 7 алфа - (епсилон -аминоалкил)- естратрини иприложението им за получаване на лекарствени средства - Google Patents

7 алфа-(ипсилон-аминоалкил)-естратрини, метод за получаването им, фармацевтични препарати съдържащитези 7 алфа - (епсилон -аминоалкил)- естратрини иприложението им за получаване на лекарствени средства Download PDF

Info

Publication number: BG62972B1
Authority: BG; Bulgaria
Prior art keywords: estra; pentyl; triene; propylamino; methyl
Prior art date: 1996-08-20

Application number

BG103185A

Other languages

Bulgarian (bg)

English (en)

Other versions

BG103185A (en

Inventor

Rolf Bohlmann

Dieter Bittler

Josef Heindi

Nikolaus Heinrich

Helmut Hofmeister

Hermann Kunzer

Gerhard Sauer

Christa Hegelehartung

Rosemarie Lichtner

Yukishige Nishino

Karsten Parczyk

Martin Schneider

Original Assignee

Schering Aktiengesellschaft

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1996-08-20

Filing date

1999-02-16

Publication date

2000-12-29

1999-02-16 Application filed by Schering Aktiengesellschaft filed Critical Schering Aktiengesellschaft

1999-11-30 Publication of BG103185A publication Critical patent/BG103185A/xx

2000-12-29 Publication of BG62972B1 publication Critical patent/BG62972B1/bg

Links

238000002360 preparation method Methods 0.000 title claims abstract description 14
239000000825 pharmaceutical preparation Substances 0.000 title claims description 5
238000000034 method Methods 0.000 title description 5
150000001875 compounds Chemical class 0.000 claims abstract description 82
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 53
LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 29
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims abstract description 19
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 18
230000036961 partial effect Effects 0.000 claims abstract description 16
125000001424 substituent group Chemical group 0.000 claims abstract description 14
150000003839 salts Chemical class 0.000 claims abstract description 11
229910052799 carbon Chemical group 0.000 claims abstract description 8
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 8
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 7
125000005843 halogen group Chemical group 0.000 claims abstract description 7
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 7
125000002947 alkylene group Chemical group 0.000 claims abstract description 6
125000001072 heteroaryl group Chemical group 0.000 claims abstract description 6
150000007522 mineralic acids Chemical class 0.000 claims abstract description 6
150000007524 organic acids Chemical class 0.000 claims abstract description 6
125000003107 substituted aryl group Chemical group 0.000 claims abstract description 4
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims abstract description 3
125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 claims abstract 2
-1 nitroxy Chemical group 0.000 claims description 292
125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 51
VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 claims description 16
150000002009 diols Chemical class 0.000 claims description 10
239000003814 drug Substances 0.000 claims description 8
229910052731 fluorine Inorganic materials 0.000 claims description 6
229910052717 sulfur Inorganic materials 0.000 claims description 6
125000004434 sulfur atom Chemical group 0.000 claims description 6
125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 5
125000000217 alkyl group Chemical group 0.000 claims description 3
125000001153 fluoro group Chemical group F* 0.000 claims description 3
125000000623 heterocyclic group Chemical group 0.000 claims description 3
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
229910052740 iodine Inorganic materials 0.000 claims description 3
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
125000000304 alkynyl group Chemical group 0.000 claims description 2
229910052794 bromium Inorganic materials 0.000 claims description 2
229910052801 chlorine Inorganic materials 0.000 claims description 2
239000000460 chlorine Substances 0.000 claims description 2
239000003937 drug carrier Substances 0.000 claims description 2
239000011630 iodine Substances 0.000 claims description 2
150000002164 estratrienes Chemical class 0.000 claims 14
125000001183 hydrocarbyl group Chemical group 0.000 claims 3
125000005004 perfluoroethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 claims 3
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 1
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims 1
125000003342 alkenyl group Chemical group 0.000 claims 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims 1
239000011737 fluorine Substances 0.000 claims 1
230000001833 anti-estrogenic effect Effects 0.000 abstract description 21
206010028980 Neoplasm Diseases 0.000 abstract description 17
239000000328 estrogen antagonist Substances 0.000 abstract description 13
229940046836 anti-estrogen Drugs 0.000 abstract description 12
230000000694 effects Effects 0.000 abstract description 8
125000006527 (C1-C5) alkyl group Chemical group 0.000 abstract description 4
239000001257 hydrogen Substances 0.000 abstract description 4
229910052739 hydrogen Inorganic materials 0.000 abstract description 4
125000004429 atom Chemical group 0.000 abstract description 3
125000001893 nitrooxy group Chemical group [O-][N+](=O)O* 0.000 abstract description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 abstract 2
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 abstract 1
150000001721 carbon Chemical group 0.000 abstract 1
238000001794 hormone therapy Methods 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 446
239000000243 solution Substances 0.000 description 282
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 231
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 228
235000019439 ethyl acetate Nutrition 0.000 description 144
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 118
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 117
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 112
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 110
239000000741 silica gel Substances 0.000 description 109
229910002027 silica gel Inorganic materials 0.000 description 109
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 106
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 105
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 99
229910052938 sodium sulfate Inorganic materials 0.000 description 98
235000011152 sodium sulphate Nutrition 0.000 description 98
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 69
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 57
239000003921 oil Substances 0.000 description 56
235000019198 oils Nutrition 0.000 description 55
239000011541 reaction mixture Substances 0.000 description 55
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 54
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 53
235000002639 sodium chloride Nutrition 0.000 description 49
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 46
239000012043 crude product Substances 0.000 description 45
239000006260 foam Substances 0.000 description 41
239000011780 sodium chloride Substances 0.000 description 40
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 36
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 32
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 30
OSVMTWJCGUFAOD-KZQROQTASA-N formestane Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1O OSVMTWJCGUFAOD-KZQROQTASA-N 0.000 description 28
229910000030 sodium bicarbonate Inorganic materials 0.000 description 27
235000017557 sodium bicarbonate Nutrition 0.000 description 27
238000004587 chromatography analysis Methods 0.000 description 25
239000012074 organic phase Substances 0.000 description 25
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 24
JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 24
AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 22
230000007935 neutral effect Effects 0.000 description 22
238000006243 chemical reaction Methods 0.000 description 21
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 20
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 20
239000000203 mixture Substances 0.000 description 20
238000003756 stirring Methods 0.000 description 20
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 18
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 18
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
229940011871 estrogen Drugs 0.000 description 18
239000000262 estrogen Substances 0.000 description 18
238000012360 testing method Methods 0.000 description 17
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 16
239000013078 crystal Substances 0.000 description 16
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 15
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
238000001816 cooling Methods 0.000 description 15
239000005457 ice water Substances 0.000 description 15
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 15
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 14
241001465754 Metazoa Species 0.000 description 14
239000000047 product Substances 0.000 description 14
238000012545 processing Methods 0.000 description 13
238000011282 treatment Methods 0.000 description 13
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
229960000583 acetic acid Drugs 0.000 description 12
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 11
NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 10
210000004027 cell Anatomy 0.000 description 10
QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 description 10
HSZCZNFXUDYRKD-UHFFFAOYSA-M lithium iodide Chemical compound [Li+].[I-] HSZCZNFXUDYRKD-UHFFFAOYSA-M 0.000 description 10
229910052757 nitrogen Inorganic materials 0.000 description 10
150000003431 steroids Chemical group 0.000 description 10
241000700159 Rattus Species 0.000 description 9
230000001419 dependent effect Effects 0.000 description 9
239000012279 sodium borohydride Substances 0.000 description 9
229910000033 sodium borohydride Inorganic materials 0.000 description 9
239000013543 active substance Substances 0.000 description 8
WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 8
235000009518 sodium iodide Nutrition 0.000 description 8
239000000126 substance Substances 0.000 description 8
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 8
LGHBWDKMGOIZKH-CBZIJGRNSA-N 3-Deoxyestrone Chemical compound C1=CC=C2[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 LGHBWDKMGOIZKH-CBZIJGRNSA-N 0.000 description 7
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 7
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 7
230000009471 action Effects 0.000 description 7
238000001704 evaporation Methods 0.000 description 7
230000008020 evaporation Effects 0.000 description 7
239000011777 magnesium Substances 0.000 description 7
229910052749 magnesium Inorganic materials 0.000 description 7
229910052943 magnesium sulfate Inorganic materials 0.000 description 7
235000019341 magnesium sulphate Nutrition 0.000 description 7
239000000725 suspension Substances 0.000 description 7
238000005406 washing Methods 0.000 description 7
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 6
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 6
239000008346 aqueous phase Substances 0.000 description 6
239000012267 brine Substances 0.000 description 6
238000010790 dilution Methods 0.000 description 6
239000012895 dilution Substances 0.000 description 6
GUVUOGQBMYCBQP-UHFFFAOYSA-N dmpu Chemical compound CN1CCCN(C)C1=O GUVUOGQBMYCBQP-UHFFFAOYSA-N 0.000 description 6
150000002148 esters Chemical class 0.000 description 6
NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 6
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 6
235000006408 oxalic acid Nutrition 0.000 description 6
229910000027 potassium carbonate Inorganic materials 0.000 description 6
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
239000002904 solvent Substances 0.000 description 6
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
PCCWBPBISLLZHG-QMMMGPOBSA-N (2s)-2-(4,4,5,5,5-pentafluoropentylsulfanylmethyl)pyrrolidine Chemical compound FC(F)(F)C(F)(F)CCCSC[C@@H]1CCCN1 PCCWBPBISLLZHG-QMMMGPOBSA-N 0.000 description 5
229910021590 Copper(II) bromide Inorganic materials 0.000 description 5
KNEDKVNOOUXJMU-OYNJSTQKSA-N [(13s)-1-acetyloxy-13-methyl-17-oxo-7,8,9,11,12,14,15,16-octahydro-6h-cyclopenta[a]phenanthren-4-yl] acetate Chemical compound C12CC[C@]3(C)C(=O)CCC3C2CCC2=C1C(OC(C)=O)=CC=C2OC(=O)C KNEDKVNOOUXJMU-OYNJSTQKSA-N 0.000 description 5
239000002253 acid Substances 0.000 description 5
235000019270 ammonium chloride Nutrition 0.000 description 5
239000003153 chemical reaction reagent Substances 0.000 description 5
LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 5
230000001076 estrogenic effect Effects 0.000 description 5
230000012010 growth Effects 0.000 description 5
229940088597 hormone Drugs 0.000 description 5
239000005556 hormone Substances 0.000 description 5
150000002430 hydrocarbons Chemical group 0.000 description 5
229910052751 metal Inorganic materials 0.000 description 5
239000002184 metal Substances 0.000 description 5
239000012299 nitrogen atmosphere Substances 0.000 description 5
239000002244 precipitate Substances 0.000 description 5
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
229960001603 tamoxifen Drugs 0.000 description 5
SDFSOVJPEVLDIN-YLCSIZAYSA-N (7r,8r,9s,10r,13s,14s)-7-(5-chloropentyl)-13-methyl-1,2,6,7,8,9,10,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthrene-3,17-dione Chemical compound C([C@@H]12)CC(=O)C=C1C[C@@H](CCCCCCl)[C@@H]1[C@@H]2CC[C@@]2(C)[C@H]1CCC2=O SDFSOVJPEVLDIN-YLCSIZAYSA-N 0.000 description 4
KOZQNKNVCXHJPO-UHFFFAOYSA-N 5-bromopentoxy-tert-butyl-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)OCCCCCBr KOZQNKNVCXHJPO-UHFFFAOYSA-N 0.000 description 4
ARSRBNBHOADGJU-UHFFFAOYSA-N 7,12-dimethyltetraphene Chemical compound C1=CC2=CC=CC=C2C2=C1C(C)=C(C=CC=C1)C1=C2C ARSRBNBHOADGJU-UHFFFAOYSA-N 0.000 description 4
UYIFTLBWAOGQBI-BZDYCCQFSA-N Benzhormovarine Chemical compound C([C@@H]1[C@@H](C2=CC=3)CC[C@]4([C@H]1CC[C@@H]4O)C)CC2=CC=3OC(=O)C1=CC=CC=C1 UYIFTLBWAOGQBI-BZDYCCQFSA-N 0.000 description 4
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 4
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
230000001270 agonistic effect Effects 0.000 description 4
201000008275 breast carcinoma Diseases 0.000 description 4
JYYOBHFYCIDXHH-UHFFFAOYSA-N carbonic acid;hydrate Chemical compound O.OC(O)=O JYYOBHFYCIDXHH-UHFFFAOYSA-N 0.000 description 4
238000011161 development Methods 0.000 description 4
229930182833 estradiol Natural products 0.000 description 4
229950002007 estradiol benzoate Drugs 0.000 description 4
239000012362 glacial acetic acid Substances 0.000 description 4
AOGQPLXWSUTHQB-UHFFFAOYSA-N hexyl acetic acid ester Natural products CCCCCCOC(C)=O AOGQPLXWSUTHQB-UHFFFAOYSA-N 0.000 description 4
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
WJJPQJZQCKZMDG-UHFFFAOYSA-N n-methyl-3-(4,4,5,5,5-pentafluoropentylsulfanyl)propan-1-amine Chemical compound CNCCCSCCCC(F)(F)C(F)(F)F WJJPQJZQCKZMDG-UHFFFAOYSA-N 0.000 description 4
239000008194 pharmaceutical composition Substances 0.000 description 4
229920006395 saturated elastomer Polymers 0.000 description 4
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 4
210000004291 uterus Anatomy 0.000 description 4
GKSFRYHLOMZMFQ-QXUSFIETSA-N (8r,9s,10r,13s,14s)-13-methyl-1,2,8,9,10,11,12,14,15,16-decahydrocyclopenta[a]phenanthrene-3,17-dione Chemical compound O=C1CC[C@@H]2[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3C=CC2=C1 GKSFRYHLOMZMFQ-QXUSFIETSA-N 0.000 description 3
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WHGYBXFWUBPSRW-FEYSZYNQSA-N β-dextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)C(O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FEYSZYNQSA-N 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J53/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by condensation with a carbocyclic rings or by formation of an additional ring by means of a direct link between two ring carbon atoms, including carboxyclic rings fused to the cyclopenta(a)hydrophenanthrene skeleton are included in this class
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J53/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by condensation with a carbocyclic rings or by formation of an additional ring by means of a direct link between two ring carbon atoms, including carboxyclic rings fused to the cyclopenta(a)hydrophenanthrene skeleton are included in this class
- C07J53/002—Carbocyclic rings fused
- C07J53/004—3 membered carbocyclic rings
- C07J53/008—3 membered carbocyclic rings in position 15/16
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/32—Antioestrogens
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
- C07J41/0033—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005
- C07J41/0072—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 the A ring of the steroid being aromatic
- 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
- C07J43/006—Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton spiro-condensed
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J53/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by condensation with a carbocyclic rings or by formation of an additional ring by means of a direct link between two ring carbon atoms, including carboxyclic rings fused to the cyclopenta(a)hydrophenanthrene skeleton are included in this class
- C07J53/002—Carbocyclic rings fused

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Veterinary Medicine (AREA)
Animal Behavior & Ethology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Bioinformatics & Cheminformatics (AREA)
Endocrinology (AREA)
Engineering & Computer Science (AREA)
Diabetes (AREA)
Steroid Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

BG103185A 1996-08-20 1999-02-16 7 алфа-(ипсилон-аминоалкил)-естратрини, метод за получаването им, фармацевтични препарати съдържащитези 7 алфа - (епсилон -аминоалкил)- естратрини иприложението им за получаване на лекарствени средства BG62972B1 (bg)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
DE19635525A DE19635525A1 (de)	1996-08-20	1996-08-20	7alpha-(xi-Aminoalkyl)-estratriene, Verfahren zu deren Herstellung, pharmazeutische Präparate, die diese 7alpha(xi-Aminoalkyl-estratriene enthalten sowie deren Verwendung zur Herstellung von Arzneimitteln
PCT/EP1997/004517 WO1998007740A1 (de)	1996-08-20	1997-08-20	7α-(κ-AMINOALKYL)-ESTRATRIENE, VERFAHREN ZU DEREN HERSTELLUNG, PHARMAZEUTISCHE PRÄPARATE, DIE DIESE 7α-(κ-AMINOALKYL)-ESTRATRIENE ENTHALTEN SOWIE DEREN VERWENDUNG ZUR HERSTELLUNG VON ARZNEIMITTELN

Publications (2)

Publication Number	Publication Date
BG103185A BG103185A (en)	1999-11-30
BG62972B1 true BG62972B1 (bg)	2000-12-29

Family

ID=7804367

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
BG103185A BG62972B1 (bg)	1996-08-20	1999-02-16	7 алфа-(ипсилон-аминоалкил)-естратрини, метод за получаването им, фармацевтични препарати съдържащитези 7 алфа - (епсилон -аминоалкил)- естратрини иприложението им за получаване на лекарствени средства

Country Status (29)

Country	Link
EP (1)	EP0920441B1 (es)
JP (1)	JP2001503024A (es)
KR (1)	KR20000068261A (es)
CN (1)	CN1231670A (es)
AR (1)	AR009278A1 (es)
AT (1)	ATE231882T1 (es)
AU (1)	AU728843B2 (es)
BG (1)	BG62972B1 (es)
BR (1)	BR9711328A (es)
CA (1)	CA2263708A1 (es)
CZ (1)	CZ57999A3 (es)
DE (2)	DE19635525A1 (es)
DK (1)	DK0920441T3 (es)
EA (1)	EA001577B1 (es)
EE (1)	EE04021B1 (es)
ES (1)	ES2191857T3 (es)
HU (1)	HUP9903106A3 (es)
IL (1)	IL128601A (es)
IS (1)	IS4976A (es)
NO (1)	NO315655B1 (es)
NZ (1)	NZ334277A (es)
PL (1)	PL186309B1 (es)
PT (1)	PT920441E (es)
SK (1)	SK18899A3 (es)
TR (1)	TR199900432T2 (es)
TW (1)	TW552267B (es)
UA (1)	UA50792C2 (es)
WO (1)	WO1998007740A1 (es)
ZA (1)	ZA977482B (es)

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CN101312944B (zh)	2005-11-22	2013-03-06	住友化学株式会社	有机硫化合物及其作为节肢动物杀灭剂的应用
DE102007023614A1 (de)	2007-05-21	2008-11-27	Bayer Schering Pharma Aktiengesellschaft	Nichtsteroidale Progesteronrezeptor-Modulatoren
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JP2009001551A (ja)	2007-05-18	2009-01-08	Sumitomo Chemical Co Ltd	有機硫黄化合物及びその有害節足動物防除用途
JP5298631B2 (ja)	2007-05-18	2013-09-25	住友化学株式会社	有機硫黄化合物及びその有害節足動物防除用途
TW200904329A (en)	2007-05-18	2009-02-01	Sumitomo Chemical Co	Organic sulfur compound and its use for controlling harmful arthropod
DE102007032800A1 (de)	2007-07-10	2009-01-15	Bayer Schering Pharma Aktiengesellschaft	Nichtsteroidale Progesteronrezeptor-Modulatoren
NZ585389A (en)	2007-10-16	2011-10-28	Repros Therapeutics Inc	Trans-clomiphene for metabolic syndrome
DE102007058747A1 (de)	2007-12-05	2009-06-10	Bayer Schering Pharma Aktiengesellschaft	Nichtsteroidale Progesteronrezeptor-Modulatoren
EP2070909A1 (de)	2007-12-15	2009-06-17	Bayer Schering Pharma AG	Nichtsteroidale Progesteronrezeptor-Modulatoren
EP2070941A1 (en)	2007-12-14	2009-06-17	Bayer Schering Pharma Aktiengesellschaft	Stereoselective synthesis of selective estrogen receptor down-regulators
DE102008057230A1 (de)	2008-11-11	2010-05-12	Bayer Schering Pharma Aktiengesellschaft	Synergistische pharmazeutische Kombination mit einem Estrogenrezeptorantagonisten und einem Progestin
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EP2258375A1 (de)	2009-06-04	2010-12-08	Bayer Schering Pharma Aktiengesellschaft	17B-alkyl-17alpha-oxy-estratriene
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DE102009034362A1 (de)	2009-07-20	2011-01-27	Bayer Schering Pharma Aktiengesellschaft	17-Hydroxy-17-pentafluorethyl-estra-4,9(10)-dien-11-aryl-Derivate, Verfahren zu ihrer Herstellung und ihre Verwendung zur Behandlung von Krankheiten
DE102009034366A1 (de)	2009-07-20	2011-01-27	Bayer Schering Pharma Aktiengesellschaft	17-Hydroxy-17-pentafluorethyl-estra-4,9(10)-dien-11-methylenoxyalkylenaryl-Derivate, Verfahren zu ihrer Herstellung und ihre Verwendung zur Behandlung von Krankheiten
DE102009034368A1 (de)	2009-07-20	2011-01-27	Bayer Schering Pharma Aktiengesellschaft	17-Hydroxy-17-pentafluorethyl-estra-4,9(10)-dien-11-acyloxyalkylenphenyl-Derivate, Verfahren zu ihrer Herstellung und ihre Verwendung zur Behandlung von Krankheiten
DE102009034525A1 (de)	2009-07-21	2011-01-27	Bayer Schering Pharma Aktiengesellschaft	17-Hydroxy-17-pentafluorethyl-estra-4,9(10)-dien-11-aryl-Derivate, Verfahren zu ihrer Herstellung und ihre Verwendung zur Behandlung von Krankheiten
DE102009034526A1 (de)	2009-07-21	2011-02-10	Bayer Schering Pharma Aktiengesellschaft	17-Hydroxy-17-pentafluorethyl-estra-4,9(10)-dien-11-ethinylphenyl-Derivate, Verfahren zu deren Herstellung und deren Verwendung zur Behandlung von Krankheiten
WO2011092127A1 (en)	2010-01-26	2011-08-04	Bayer Schering Pharma Aktiengesellschaft	14,17-bridged estratriene derivatives comprising heterocyclic bioisosteres for the phenolic a-ring
DE102010007719A1 (de)	2010-02-10	2011-08-11	Bayer Schering Pharma Aktiengesellschaft, 13353	Progesteronrezeptorantagonisten
DE102010007722A1 (de)	2010-02-10	2011-08-11	Bayer Schering Pharma Aktiengesellschaft, 13353	Progesteronrezeptorantagonisten
KR20170127044A (ko)	2010-06-16	2017-11-20	앙도르쉐르슈 인코포레이티드	에스트로겐-관련 질병의 치료 또는 예방 방법
DE102010030538A1 (de)	2010-06-25	2011-12-29	Bayer Schering Pharma Aktiengesellschaft	6,7-Dihydro-5H-benzo[7]annulen-Derivate, Verfahren zu ihrer Herstellung, pharmazeutische Präparate die diese enthalten, sowie deren Verwendung zur Herstellung von Arzneimitteln
DE102011004899A1 (de)	2011-03-01	2012-09-06	Bayer Pharma Aktiengesellschaft	17-Hydroxy-17-pentafluorethyl-estra-4,9(10)-dien-11-aryl-Derivate, Verfahren zu ihrer Herstellung und ihre Verwendung zur Behandlung von Krankheiten
PT2753632T (pt)	2011-09-08	2023-08-17	Sage Therapeutics Inc	Esteróides neuroactivos, composições e respectivas utilizações
DE102011087987A1 (de)	2011-12-08	2013-06-13	Bayer Intellectual Property Gmbh	6,7-Dihydro-5H-benzo[7]annulen-Derivate, Verfahren zu ihrer Herstellung, pharmazeutische Präparate die diese enthalten, sowie deren Verwendung zur Herstellung von Arzneimitteln
ES2681023T3 (es)	2012-02-29	2018-09-11	Repros Therapeutics Inc.	Terapia de combinación para tratar el déficit de andrógenos
SMT202500336T1 (it)	2013-03-13	2025-11-10	Sage Therapeutics Inc	Steroidi neuroattivi e loro metodi di utilizzo
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EP2987799B1 (en) *	2013-04-18	2020-04-08	Xi'an Libang Pharmaceutical Technology Co.,ltd.	Ester derivative of 7-alpha-[9-(4,4,5,5,5-pentafluoropentylsulphinyl)nonyl]oestra-1,3,5(10)-triene-3,17beta-diol having antitumour activity and preparation method thereof
WO2015195967A1 (en)	2014-06-18	2015-12-23	Sage Therapeutics, Inc.	Oxysterols and methods of use thereof
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US11633382B2 (en)	2015-11-10	2023-04-25	Paracrine Therapeutics Ab	Treatment of ER-negative breast cancer with an PDGF-CC inhibitor and anti-estrogen
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TWI752976B (zh)	2016-07-07	2022-01-21	美商賽吉醫療公司	氧固醇(oxysterol)及其使用方法
CA3038900A1 (en)	2016-09-30	2018-04-05	Sage Therapeutics, Inc.	C7 substituted oxysterols and methods as nmda modulators
CN115322238A (zh)	2016-10-18	2022-11-11	萨奇治疗股份有限公司	氧甾醇及其使用方法
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1996
- 1996-08-20 DE DE19635525A patent/DE19635525A1/de not_active Withdrawn
1997
- 1997-08-20 ZA ZA9707482A patent/ZA977482B/xx unknown
- 1997-08-20 HU HU9903106A patent/HUP9903106A3/hu unknown
- 1997-08-20 DE DE59709239T patent/DE59709239D1/de not_active Expired - Fee Related
- 1997-08-20 CN CN97198245A patent/CN1231670A/zh active Pending
- 1997-08-20 UA UA99031552A patent/UA50792C2/uk unknown
- 1997-08-20 BR BR9711328A patent/BR9711328A/pt unknown
- 1997-08-20 WO PCT/EP1997/004517 patent/WO1998007740A1/de not_active Ceased
- 1997-08-20 PL PL97331863A patent/PL186309B1/pl not_active IP Right Cessation
- 1997-08-20 EP EP97943814A patent/EP0920441B1/de not_active Expired - Lifetime
- 1997-08-20 TW TW086111927A patent/TW552267B/zh active
- 1997-08-20 IL IL12860197A patent/IL128601A/xx not_active IP Right Cessation
- 1997-08-20 NZ NZ334277A patent/NZ334277A/xx unknown
- 1997-08-20 ES ES97943814T patent/ES2191857T3/es not_active Expired - Lifetime
- 1997-08-20 EA EA199900210A patent/EA001577B1/ru not_active IP Right Cessation
- 1997-08-20 DK DK97943814T patent/DK0920441T3/da active
- 1997-08-20 JP JP10510412A patent/JP2001503024A/ja not_active Ceased
- 1997-08-20 AR ARP970103779A patent/AR009278A1/es not_active Application Discontinuation
- 1997-08-20 CZ CZ99579A patent/CZ57999A3/cs unknown
- 1997-08-20 TR TR1999/00432T patent/TR199900432T2/xx unknown
- 1997-08-20 CA CA002263708A patent/CA2263708A1/en not_active Abandoned
- 1997-08-20 KR KR1019997001396A patent/KR20000068261A/ko not_active Ceased
- 1997-08-20 SK SK188-99A patent/SK18899A3/sk unknown
- 1997-08-20 EE EEP199900075A patent/EE04021B1/xx not_active IP Right Cessation
- 1997-08-20 PT PT97943814T patent/PT920441E/pt unknown
- 1997-08-20 AU AU45520/97A patent/AU728843B2/en not_active Ceased
- 1997-08-20 AT AT97943814T patent/ATE231882T1/de not_active IP Right Cessation
1999
- 1999-02-11 IS IS4976A patent/IS4976A/is unknown
- 1999-02-16 BG BG103185A patent/BG62972B1/bg unknown
- 1999-02-19 NO NO19990793A patent/NO315655B1/no not_active IP Right Cessation

Also Published As

Publication number	Publication date
HUP9903106A2 (hu)	2000-03-28
PL331863A1 (en)	1999-08-16
EP0920441A1 (de)	1999-06-09
DK0920441T3 (da)	2003-05-26
IS4976A (is)	1999-02-11
PT920441E (pt)	2003-06-30
CA2263708A1 (en)	1998-02-26
BR9711328A (pt)	1999-08-17
NO990793D0 (no)	1999-02-19
CZ57999A3 (cs)	1999-08-11
CN1231670A (zh)	1999-10-13
DE19635525A1 (de)	1998-02-26
NO315655B1 (no)	2003-10-06
HUP9903106A3 (en)	2000-05-29
BG103185A (en)	1999-11-30
DE59709239D1 (de)	2003-03-06
NO990793L (no)	1999-04-20
EA001577B1 (ru)	2001-06-25
ATE231882T1 (de)	2003-02-15
IL128601A (en)	2003-07-31
JP2001503024A (ja)	2001-03-06
WO1998007740A1 (de)	1998-02-26
IL128601A0 (en)	2000-01-31
PL186309B1 (pl)	2003-12-31
ZA977482B (en)	1998-02-23
AR009278A1 (es)	2000-04-12
SK18899A3 (en)	1999-08-06
AU728843B2 (en)	2001-01-18
ES2191857T3 (es)	2003-09-16
UA50792C2 (uk)	2002-11-15
EE9900075A (et)	1999-10-15
KR20000068261A (ko)	2000-11-25
EE04021B1 (et)	2003-04-15
EP0920441B1 (de)	2003-01-29
TW552267B (en)	2003-09-11
TR199900432T2 (xx)	1999-04-21
AU4552097A (en)	1998-03-06
NZ334277A (en)	2000-10-27
EA199900210A1 (ru)	1999-08-26

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