CA2692997A1 - DÉRIVÉ DE 17ß-CYANO-19-ANDROST-4-ÈNE, SON UTILISATION, ET MÉDICAMENT CONTENANT CE DÉRIVÉ - Google Patents

DÉRIVÉ DE 17ß-CYANO-19-ANDROST-4-ÈNE, SON UTILISATION, ET MÉDICAMENT CONTENANT CE DÉRIVÉ Download PDF

Info

Publication number: CA2692997A1
Authority: CA; Canada
Prior art keywords: beta; cyano; alpha; methyleneandrost; cyanoandrost
Prior art date: 2007-06-12
Legal status (The legal status 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 status listed.): Abandoned

Application number

CA 2692997

Other languages

English (en)

Inventor

Joachim Kuhnke

Jan Huebner

Rolf Bohlmann

Thomas Frenzel

Ulrich Klar

Frederik Menges

Sven Ring

Steffen Borden

Hans-Peter Muhn

Katja Prelle

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Bayer Intellectual Property GmbH

Original Assignee

Individual

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.)

2007-06-12

Filing date

2008-06-12

Publication date

2008-12-18

2008-06-12 Application filed by Individual filed Critical Individual

2008-12-18 Publication of CA2692997A1 publication Critical patent/CA2692997A1/fr

Status Abandoned legal-status Critical Current

Links

239000003814 drug Substances 0.000 title claims description 20
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 71
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims abstract description 43
239000001257 hydrogen Substances 0.000 claims abstract description 42
150000001875 compounds Chemical class 0.000 claims abstract description 35
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 33
-1 hydroxymethylene Chemical group 0.000 claims abstract description 25
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 23
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 20
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims abstract description 20
239000000126 substance Substances 0.000 claims abstract description 20
230000015572 biosynthetic process Effects 0.000 claims abstract description 18
230000003152 gestagenic effect Effects 0.000 claims abstract description 15
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims abstract description 8
150000004677 hydrates Chemical class 0.000 claims abstract description 6
239000012453 solvate Substances 0.000 claims abstract description 6
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims abstract description 5
125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims abstract description 5
150000003839 salts Chemical class 0.000 claims abstract description 5
229910052736 halogen Chemical group 0.000 claims abstract description 4
150000002367 halogens Chemical group 0.000 claims abstract description 4
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract 6
239000000460 chlorine Chemical group 0.000 claims description 22
239000000262 estrogen Substances 0.000 claims description 18
206010027304 Menopausal symptoms Diseases 0.000 claims description 13
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
239000000654 additive Substances 0.000 claims description 4
230000000996 additive effect Effects 0.000 claims description 4
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
BFPYWIDHMRZLRN-SLHNCBLASA-N Ethinyl estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 BFPYWIDHMRZLRN-SLHNCBLASA-N 0.000 claims description 3
229910052801 chlorine Chemical group 0.000 claims description 3
229960002568 ethinylestradiol Drugs 0.000 claims description 3
238000004519 manufacturing process Methods 0.000 claims description 3
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 2
RSEPBGGWRJCQGY-RBRWEJTLSA-N Estradiol valerate Chemical compound C1CC2=CC(O)=CC=C2[C@@H]2[C@@H]1[C@@H]1CC[C@H](OC(=O)CCCC)[C@@]1(C)CC2 RSEPBGGWRJCQGY-RBRWEJTLSA-N 0.000 claims description 2
229930182833 estradiol Natural products 0.000 claims description 2
125000001424 substituent group Chemical group 0.000 claims description 2
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims 1
150000002431 hydrogen Chemical class 0.000 abstract 3
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 102
238000000034 method Methods 0.000 description 56
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 56
239000000243 solution Substances 0.000 description 53
239000000203 mixture Substances 0.000 description 49
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 30
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 23
239000000741 silica gel Substances 0.000 description 21
229910002027 silica gel Inorganic materials 0.000 description 21
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 19
238000003818 flash chromatography Methods 0.000 description 17
239000012074 organic phase Substances 0.000 description 17
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 16
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 16
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
229910052938 sodium sulfate Inorganic materials 0.000 description 15
235000011152 sodium sulphate Nutrition 0.000 description 15
238000006243 chemical reaction Methods 0.000 description 13
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
238000004587 chromatography analysis Methods 0.000 description 11
238000002360 preparation method Methods 0.000 description 11
239000002904 solvent Substances 0.000 description 10
150000003431 steroids Chemical group 0.000 description 9
238000003756 stirring Methods 0.000 description 9
HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical compound C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 description 8
METQSPRSQINEEU-HXCATZOESA-N drospirenone Chemical compound C([C@]12[C@H]3C[C@H]3[C@H]3[C@H]4[C@@H]([C@]5(CCC(=O)C=C5[C@@H]5C[C@@H]54)C)CC[C@@]31C)CC(=O)O2 METQSPRSQINEEU-HXCATZOESA-N 0.000 description 8
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 8
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 8
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 8
238000002425 crystallisation Methods 0.000 description 7
230000008025 crystallization Effects 0.000 description 7
METQSPRSQINEEU-UHFFFAOYSA-N dihydrospirorenone Natural products CC12CCC(C3(CCC(=O)C=C3C3CC33)C)C3C1C1CC1C21CCC(=O)O1 METQSPRSQINEEU-UHFFFAOYSA-N 0.000 description 7
229960004845 drospirenone Drugs 0.000 description 7
238000001035 drying Methods 0.000 description 7
239000011541 reaction mixture Substances 0.000 description 7
238000003786 synthesis reaction Methods 0.000 description 7
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 7
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
239000012043 crude product Substances 0.000 description 6
239000000047 product Substances 0.000 description 6
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
241000700159 Rattus Species 0.000 description 5
239000002253 acid Substances 0.000 description 5
BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 5
238000012423 maintenance Methods 0.000 description 5
150000002825 nitriles Chemical class 0.000 description 5
230000035935 pregnancy Effects 0.000 description 5
239000000583 progesterone congener Substances 0.000 description 5
238000000926 separation method Methods 0.000 description 5
239000007858 starting material Substances 0.000 description 5
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 4
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
229910052783 alkali metal Inorganic materials 0.000 description 4
230000002280 anti-androgenic effect Effects 0.000 description 4
239000002585 base Substances 0.000 description 4
239000003054 catalyst Substances 0.000 description 4
229940125782 compound 2 Drugs 0.000 description 4
238000001816 cooling Methods 0.000 description 4
238000001914 filtration Methods 0.000 description 4
238000004128 high performance liquid chromatography Methods 0.000 description 4
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 4
AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 4
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 4
238000002953 preparative HPLC Methods 0.000 description 4
150000003254 radicals Chemical class 0.000 description 4
208000024891 symptom Diseases 0.000 description 4
239000003826 tablet Substances 0.000 description 4
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 4
238000005406 washing Methods 0.000 description 4
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 3
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
241001465754 Metazoa Species 0.000 description 3
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 3
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
229910052794 bromium Inorganic materials 0.000 description 3
230000003197 catalytic effect Effects 0.000 description 3
239000003153 chemical reaction reagent Substances 0.000 description 3
239000013078 crystal Substances 0.000 description 3
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
229960001760 dimethyl sulfoxide Drugs 0.000 description 3
230000000694 effects Effects 0.000 description 3
230000008030 elimination Effects 0.000 description 3
238000003379 elimination reaction Methods 0.000 description 3
238000006735 epoxidation reaction Methods 0.000 description 3
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 3
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
238000001727 in vivo Methods 0.000 description 3
239000000543 intermediate Substances 0.000 description 3
ARZGTTMMEJDPHG-UHFFFAOYSA-N n-benzyl-2-(2,2-dimethyl-4-phenyloxan-4-yl)ethanamine Chemical compound C1COC(C)(C)CC1(C=1C=CC=CC=1)CCNCC1=CC=CC=C1 ARZGTTMMEJDPHG-UHFFFAOYSA-N 0.000 description 3
150000002923 oximes Chemical class 0.000 description 3
239000012071 phase Substances 0.000 description 3
238000009597 pregnancy test Methods 0.000 description 3
230000002829 reductive effect Effects 0.000 description 3
229920006395 saturated elastomer Polymers 0.000 description 3
239000001632 sodium acetate Substances 0.000 description 3
235000017281 sodium acetate Nutrition 0.000 description 3
229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
235000017557 sodium bicarbonate Nutrition 0.000 description 3
239000011780 sodium chloride Substances 0.000 description 3
239000000725 suspension Substances 0.000 description 3
238000012360 testing method Methods 0.000 description 3
BPLKQGGAXWRFOE-UHFFFAOYSA-M trimethylsulfoxonium iodide Chemical compound [I-].C[S+](C)(C)=O BPLKQGGAXWRFOE-UHFFFAOYSA-M 0.000 description 3
238000010626 work up procedure Methods 0.000 description 3
KLNWLDZOCLFNHL-IWMPCEKISA-N (5S,8S,9S,10S,13S,14S)-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-3-carbonitrile Chemical compound C(#N)C1C[C@@H]2CC[C@@H]3[C@H](CC[C@@]4(CCC[C@H]43)C)[C@]2(CC1)C KLNWLDZOCLFNHL-IWMPCEKISA-N 0.000 description 2
KJNCXCNYMUMSRD-DEPCRRQNSA-N (8r,9s,10r,13r,14r)-10,13-dimethyl-15-methylidene-2,6,7,8,9,11,12,14,16,17-decahydro-1h-cyclopenta[a]phenanthren-3-one Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C(=C)CC[C@@]1(C)CC2 KJNCXCNYMUMSRD-DEPCRRQNSA-N 0.000 description 2
SGUVLZREKBPKCE-UHFFFAOYSA-N 1,5-diazabicyclo[4.3.0]-non-5-ene Chemical compound C1CCN=C2CCCN21 SGUVLZREKBPKCE-UHFFFAOYSA-N 0.000 description 2
OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 2
CECJZCIBAVDJJE-UHFFFAOYSA-N 2-nitro-4-pentyl-1-(4-pentylphenyl)benzene Chemical compound C1=CC(CCCCC)=CC=C1C1=CC=C(CCCCC)C=C1[N+]([O-])=O CECJZCIBAVDJJE-UHFFFAOYSA-N 0.000 description 2
QGXBDMJGAMFCBF-HLUDHZFRSA-N 5α-Androsterone 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-HLUDHZFRSA-N 0.000 description 2
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
101150041968 CDC13 gene Proteins 0.000 description 2
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical group O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
239000006144 Dulbecco’s modiﬁed Eagle's medium Substances 0.000 description 2
DNXHEGUUPJUMQT-CBZIJGRNSA-N Estrone Chemical compound OC1=CC=C2[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 DNXHEGUUPJUMQT-CBZIJGRNSA-N 0.000 description 2
206010055690 Foetal death Diseases 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 2
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 2
230000002378 acidificating effect Effects 0.000 description 2
239000002168 alkylating agent Substances 0.000 description 2
229940100198 alkylating agent Drugs 0.000 description 2
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
230000008485 antagonism Effects 0.000 description 2
230000001833 anti-estrogenic effect Effects 0.000 description 2
125000004429 atom Chemical group 0.000 description 2
SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 2
238000009835 boiling Methods 0.000 description 2
230000031709 bromination Effects 0.000 description 2
238000005893 bromination reaction Methods 0.000 description 2
239000002775 capsule Substances 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
KQIADDMXRMTWHZ-UHFFFAOYSA-N chloro-tri(propan-2-yl)silane Chemical compound CC(C)[Si](Cl)(C(C)C)C(C)C KQIADDMXRMTWHZ-UHFFFAOYSA-N 0.000 description 2
IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 2
125000004122 cyclic group Chemical group 0.000 description 2
150000002170 ethers Chemical class 0.000 description 2
238000002474 experimental method Methods 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
238000001640 fractional crystallisation Methods 0.000 description 2
125000000524 functional group Chemical group 0.000 description 2
150000004820 halides Chemical class 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
238000002657 hormone replacement therapy Methods 0.000 description 2
229910000042 hydrogen bromide Inorganic materials 0.000 description 2
238000005984 hydrogenation reaction Methods 0.000 description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
238000002513 implantation Methods 0.000 description 2
239000011630 iodine Substances 0.000 description 2
229910052740 iodine Inorganic materials 0.000 description 2
238000006317 isomerization reaction Methods 0.000 description 2
XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 description 2
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125000004430 oxygen atom Chemical group O* 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
229940049954 penicillin Drugs 0.000 description 1
125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
230000002093 peripheral effect Effects 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
239000006187 pill Substances 0.000 description 1
210000002826 placenta Anatomy 0.000 description 1
229920001515 polyalkylene glycol Polymers 0.000 description 1
IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 1
NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
229960002847 prasterone Drugs 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000026234 pro-estrus Effects 0.000 description 1
239000000186 progesterone Substances 0.000 description 1
229960003387 progesterone Drugs 0.000 description 1
230000000962 progestomimetic effect Effects 0.000 description 1
125000002577 pseudohalo group Chemical group 0.000 description 1
238000000746 purification Methods 0.000 description 1
229950010131 puromycin Drugs 0.000 description 1
238000006894 reductive elimination reaction Methods 0.000 description 1
230000009183 running Effects 0.000 description 1
230000007017 scission Effects 0.000 description 1
230000028043 self proteolysis Effects 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
241000894007 species Species 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
238000010186 staining Methods 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
230000003637 steroidlike Effects 0.000 description 1
229960005322 streptomycin Drugs 0.000 description 1
239000000758 substrate Substances 0.000 description 1
YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
239000001117 sulphuric acid Substances 0.000 description 1
235000011149 sulphuric acid Nutrition 0.000 description 1
239000000829 suppository Substances 0.000 description 1
GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
229960003604 testosterone Drugs 0.000 description 1
229940100640 transdermal system Drugs 0.000 description 1
238000009901 transfer hydrogenation reaction Methods 0.000 description 1
GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
210000004291 uterus Anatomy 0.000 description 1
238000001291 vacuum drying Methods 0.000 description 1
238000011121 vaginal smear Methods 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
239000011995 wilkinson's catalyst Substances 0.000 description 1
UTODFRQBVUVYOB-UHFFFAOYSA-P wilkinson's catalyst Chemical compound [Cl-].C1=CC=CC=C1P(C=1C=CC=CC=1)(C=1C=CC=CC=1)[Rh+](P(C=1C=CC=CC=1)(C=1C=CC=CC=1)C=1C=CC=CC=1)P(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 UTODFRQBVUVYOB-UHFFFAOYSA-P 0.000 description 1

Classifications

- 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
- C07J41/0094—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 containing nitrile radicals, including thiocyanide radicals
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/12—Drugs for genital or sexual disorders; Contraceptives for climacteric disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/18—Feminine contraceptives
- 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
- A61P5/34—Gestagens
- 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
- A61P5/38—Drugs for disorders of the endocrine system of the suprarenal hormones
- A61P5/42—Drugs for disorders of the endocrine system of the suprarenal hormones for decreasing, blocking or antagonising the activity of mineralocorticosteroids
- 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
- C07J53/007—3 membered carbocyclic rings in position 6-7
- 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

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
General Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
Bioinformatics & Cheminformatics (AREA)
Endocrinology (AREA)
Engineering & Computer Science (AREA)
Public Health (AREA)
Reproductive Health (AREA)
Diabetes (AREA)
Gynecology & Obstetrics (AREA)
Toxicology (AREA)
Pregnancy & Childbirth (AREA)
Steroid Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

CA 2692997 2007-06-12 2008-06-12 DÉRIVÉ DE 17ß-CYANO-19-ANDROST-4-ÈNE, SON UTILISATION, ET MÉDICAMENT CONTENANT CE DÉRIVÉ Abandoned CA2692997A1 (fr)

Applications Claiming Priority (5)

Application Number	Priority Date	Filing Date	Title
DE102007027635A DE102007027635A1 (de)	2007-06-12	2007-06-12	17ß-Cyano-19-androst-4-en-Derivat, dessen Verwendung und das Derivat enthaltende Arzneimittel
DE102007027635.6		2007-06-12
US94365107P	2007-06-13	2007-06-13
US60/943,651		2007-06-13
PCT/EP2008/057427 WO2008152112A2 (fr)	2007-06-12	2008-06-12	DÉRIVÉ DE 17β-CYANO-19-ANDROST-4-ÈNE, SON UTILISATION, ET MÉDICAMENT CONTENANT CE DÉRIVÉ

Publications (1)

Publication Number	Publication Date
CA2692997A1 true CA2692997A1 (fr)	2008-12-18

Family

ID=39986162

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA 2692997 Abandoned CA2692997A1 (fr)	2007-06-12	2008-06-12	DÉRIVÉ DE 17ß-CYANO-19-ANDROST-4-ÈNE, SON UTILISATION, ET MÉDICAMENT CONTENANT CE DÉRIVÉ

Country Status (15)

Country	Link
US (1)	US20100292184A1 (fr)
EP (1)	EP2167525A2 (fr)
JP (1)	JP2010529174A (fr)
KR (1)	KR20100037596A (fr)
CN (1)	CN101679479A (fr)
AU (1)	AU2008263857A1 (fr)
BR (1)	BRPI0812535A2 (fr)
CA (1)	CA2692997A1 (fr)
CL (1)	CL2008001720A1 (fr)
DE (1)	DE102007027635A1 (fr)
IL (1)	IL202325A0 (fr)
MX (1)	MX2009013631A (fr)
RU (1)	RU2010100337A (fr)
WO (1)	WO2008152112A2 (fr)
ZA (1)	ZA201000186B (fr)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
WO2010066349A1 (fr) *	2008-12-12	2010-06-17	Bayer Schering Pharma Aktiengesellschaft	UTILISATION DE DÉRIVÉS DE 17β-CYANO-19-ANDROST-4-ÈNE POUR PRODUIRE UN MÉDICAMENT À LIBÉRATION PROLONGÉE DESTINÉ À ÊTRE ADMINISTRÉ PAR VOIE PARENTÉRALE, ET MÉDICAMENT À LIBÉRATION PROLONGÉE CONTENANT DES DÉRIVÉS DE 17β-CYANO-19-ANDROST-4-ÈNE DESTINÉ À ÊTRE ADMINISTRÉ PAR VOIE PARENTÉRALE
WO2012059594A1 (fr)	2010-11-04	2012-05-10	Bayer Pharma Aktiengesellschaft	Antagonistes de récepteur de minéralocorticoïde pour le traitement de l'obésité induite par corticoïde
CN105085596A (zh) *	2015-08-18	2015-11-25	湖北竹溪人福药业有限责任公司	一种羧酸黄体酮的制备方法

Family Cites Families (16)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE1183500B (de)	1962-10-12	1964-12-17	Schering Ag	Verfahren zur Herstellung von alpha, beta-Methylenketonen der Steroidreihe
GB1089945A (en) *	1965-09-23	1967-11-08	British Drug Houses Ltd	Steroidal-6-spirocyclopropyl-4-en-3-ones
DE1593516C3 (de) *	1966-08-25	1975-05-15	Schering Ag, 1000 Berlin Und 4619 Bergkamen	4-Halogen-1,2 alpha; 6,7 betabismethylen-delta hoch 4-3-ketosteroide, Verfahren zu ihrer Herstellung sowie diese Steroide enthaltende Mittel
DE2109555C3 (de)	1971-02-24	1980-10-30	Schering Ag	Neue 15 a , 16 a -Methylensteroide, diese enthaltende Arzneimittel sowie Verfahren zu ihrei Herstellung
US3705179A (en)	1971-03-15	1972-12-05	American Home Prod	Antiandrogenic steroids
FR2139708B1 (fr) *	1971-06-01	1974-08-23	Roussel Uclaf
NL7701384A (nl)	1977-02-10	1978-08-14	Akzo Nv	Werkwijze voor het bereiden van nieuwe steroiden van de oestraanreeks.
DE2922500A1 (de)	1979-05-31	1980-12-04	Schering Ag	6 beta .7 beta
US4512986A (en) *	1983-07-26	1985-04-23	Research Triangle Institute	Progrestationally active steroids
DE3402329A1 (de)	1984-01-20	1985-08-01	Schering AG, 1000 Berlin und 4709 Bergkamen	6,6-ethylen-15,16-methylen-3-oxo-17(alpha)-pregn-4-en-21,17-carbolactone, verfahren zu deren herstellung und diese enthaltende pharmazeutische praeparate
ES2052550T3 (es) *	1986-10-10	1994-07-16	Roussel Uclaf	9-alfa-hidroxiesteroides, procedimiento para su preparacion y procedimiento para la preparacion de los correspondientes derivados 9(11)-deshidro.
DE19651000A1 (de)	1996-12-01	1998-06-04	Schering Ag	Oxyiminopregnancarbolactone
EP1359154A1 (fr) *	2002-04-29	2003-11-05	BOEHRINGER INGELHEIM INTERNATIONAL GmbH	Procédés supplémentaires pour la production de cyprotérone acétate
ITMI20042338A1 (it) *	2004-12-06	2005-03-06	Ind Chimica Srl	Processo per la preparazione di drospirenone
DE102004063864A1 (de) *	2004-12-30	2006-07-13	Schering Ag	18-Methyl-19-nor-17-pregn-4-en21,17-carbolactone, sowie diese enthaltende pharmazeutische Präparate
DE102007027637A1 (de) *	2007-06-12	2008-12-18	Bayer Schering Pharma Aktiengesellschaft	17ß-Cyano-19-nor-androst-4-en-Derivat, dessen Verwendung und das Derivat enthaltende Arzneimittel

2007
- 2007-06-12 DE DE102007027635A patent/DE102007027635A1/de not_active Withdrawn
2008
- 2008-06-11 CL CL2008001720A patent/CL2008001720A1/es unknown
- 2008-06-12 BR BRPI0812535A patent/BRPI0812535A2/pt not_active IP Right Cessation
- 2008-06-12 EP EP08760962A patent/EP2167525A2/fr not_active Withdrawn
- 2008-06-12 RU RU2010100337/04A patent/RU2010100337A/ru not_active Application Discontinuation
- 2008-06-12 WO PCT/EP2008/057427 patent/WO2008152112A2/fr not_active Ceased
- 2008-06-12 CN CN200880020030A patent/CN101679479A/zh active Pending
- 2008-06-12 KR KR1020107000606A patent/KR20100037596A/ko not_active Withdrawn
- 2008-06-12 JP JP2010511650A patent/JP2010529174A/ja active Pending
- 2008-06-12 US US12/664,099 patent/US20100292184A1/en not_active Abandoned
- 2008-06-12 CA CA 2692997 patent/CA2692997A1/fr not_active Abandoned
- 2008-06-12 AU AU2008263857A patent/AU2008263857A1/en not_active Abandoned
- 2008-06-12 MX MX2009013631A patent/MX2009013631A/es not_active Application Discontinuation
2009
- 2009-11-25 IL IL202325A patent/IL202325A0/en unknown
2010
- 2010-01-11 ZA ZA2010/00186A patent/ZA201000186B/en unknown

Also Published As

Publication number	Publication date
KR20100037596A (ko)	2010-04-09
WO2008152112A2 (fr)	2008-12-18
WO2008152112A3 (fr)	2009-04-30
RU2010100337A (ru)	2011-07-20
CN101679479A (zh)	2010-03-24
DE102007027635A1 (de)	2008-12-18
AU2008263857A1 (en)	2008-12-18
CL2008001720A1 (es)	2008-12-19
MX2009013631A (es)	2010-01-20
BRPI0812535A2 (pt)	2017-05-16
IL202325A0 (en)	2010-06-30
EP2167525A2 (fr)	2010-03-31
JP2010529174A (ja)	2010-08-26
US20100292184A1 (en)	2010-11-18
ZA201000186B (en)	2011-03-30

Publication	Publication Date	Title
CA2689563A1 (fr)	2008-12-18	Derive de 17beta-cyano-18a-homo-19-nor-androst-4-ene, son utilisation, et medicament contenant ce derive
RU2440365C2 (ru)	2012-01-20	18-метил-19-норандрост-4-ен-17,17-спироэфир (18-метил-19-нор-20-спирокс-4-ен-3-он) и фармацевтические препараты, которые его содержат
CN101128476A (zh)	2008-02-20	18-甲基-19-去甲-17-孕-4-烯-21,17-内酯化合物、以及包含该化合物的药物组合物
US8207150B2 (en)	2012-06-26	17β-cyano-19-nor-androst-4-ene derivative, its use and medicaments comprising the derivative
AU2008266526A1 (en)	2008-12-24	Substituted (oxazolidinon-5-yl-methyl) -2-thiophene-carboxamides and use thereof in the field of blood coagulation
CA2692997A1 (fr)	2008-12-18	DÉRIVÉ DE 17ß-CYANO-19-ANDROST-4-ÈNE, SON UTILISATION, ET MÉDICAMENT CONTENANT CE DÉRIVÉ
JP3302366B2 (ja)	2002-07-15	ゲスターゲン作用を有する１９，１１−架橋した４−エストレン
US8937058B2 (en)	2015-01-20	17-hydroxy-19-nor-21-carboxylic acid-steroid γ-lactone derivative, use thereof, and medicament containing the derivative
JP5600069B2 (ja)	2014-10-01	１７−（１’−プロペニル）−１７−３’−オキシドエストラ−４−エン−３−オン誘導体、その使用及び当該誘導体を含む医薬品
HK1141537A (en)	2010-11-12	17β-CYANO-19-ANDROST-4-ENE DERIVATIVE, USE THEREOF AND MEDICAMENTS CONTAINING SAID DERIVATIVE
HK1141535A (en)	2010-11-12	17β-CYANO-19-NOR-ANDROST-4-ENE DERIVATIVE, USE THEREOF AND MEDICAMENTS CONTAINING SAID DERIVATIVE
HK1141536A (en)	2010-11-12	17beta-cyano-18a-homo-19-nor-androst-4-ene derivative, use thereof and medicaments containing said derivative
WO2010066349A1 (fr)	2010-06-17	UTILISATION DE DÉRIVÉS DE 17β-CYANO-19-ANDROST-4-ÈNE POUR PRODUIRE UN MÉDICAMENT À LIBÉRATION PROLONGÉE DESTINÉ À ÊTRE ADMINISTRÉ PAR VOIE PARENTÉRALE, ET MÉDICAMENT À LIBÉRATION PROLONGÉE CONTENANT DES DÉRIVÉS DE 17β-CYANO-19-ANDROST-4-ÈNE DESTINÉ À ÊTRE ADMINISTRÉ PAR VOIE PARENTÉRALE
HK1151801A1 (en)	2012-02-10	15,16-METHYLENE-17-HYDROXY-19-NOR-21-CARBOXYLIC ACID γ-LACTONE DERIVATIVE, USE THEREOF, AND MEDICAMENT CONTAINING SAID DERIVATIVE
HK1151801B (en)	2014-04-17	15,16-METHYLENE-17-HYDROXY-19-NOR-21-CARBOXYLIC ACID γ-LACTONE DERIVATIVE, USE THEREOF, AND MEDICAMENT CONTAINING SAID DERIVATIVE
WO2010066354A1 (fr)	2010-06-17	UTILISATION DE DÉRIVÉS DE 17β-CYANO-18A-HOMO-19-NOR-ANDROST-4-ÈNE POUR PRODUIRE UN MÉDICAMENT À LIBÉRATION PROLONGÉE DESTINÉ À ÊTRE ADMINISTRÉ PAR VOIE PARENTÉRALE, ET MÉDICAMENT À LIBÉRATION PROLONGÉE CONTENANT DES DÉRIVÉS DE 17β-CYANO-18A-HOMO-19-NOR-ANDROST-4-ÈNE DESTINÉ À ÊTRE ADMINISTRÉ PAR VOIE PARENTÉRALE
HK1133659B (en)	2013-06-21	18-methyl-19-nor-androst-4-en-17,17-spiroether (18-methyl-19-nor-20- spirox-4-en-3-one) and pharmaceutical preparations containing the same
WO2010066355A1 (fr)	2010-06-17	UTILISATION DE DÉRIVÉS DE 17β- CYANO-19-NOR-ANDROST-4-ÈNE POUR PRODUIRE UN MÉDICAMENT À LIBÉRATION PROLONGÉE DESTINÉ À ÊTRE ADMINISTRÉ PAR VOIE PARENTÉRALE, ET MÉDICAMENT À LIBÉRATION PROLONGÉE CONTENANT DES DÉRIVÉS DE 17β- CYANO-19-NOR-ANDROST-4-ÈNE DESTINÉ À ÊTRE ADMINISTRÉ PAR VOIE PARENTÉRALE

Legal Events

Date	Code	Title	Description
2013-04-24	EEER	Examination request	Effective date: 20130416
2015-08-09	FZDE	Discontinued	Effective date: 20150612