ZA200203536B - 14,15-beta-methylene substituted androgens. - Google Patents

14,15-beta-methylene substituted androgens. Download PDF

Info

Publication number: ZA200203536B
Authority: ZA; South Africa
Prior art keywords: alkyl; hydrogen; compound according; product; methoxy
Prior art date: 1999-12-02

Application number

ZA200203536A

Other languages

English (en)

Inventor

Dirk Leysen

Roberta Buma Bursi

Jaap Van Der Louw

Marcel Evert De Gooyer

Original Assignee

Akzo Nobel Nv

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.)

1999-12-02

Filing date

2002-05-03

Publication date

2003-08-04

2002-05-03 Application filed by Akzo Nobel Nv filed Critical Akzo Nobel Nv

2003-08-04 Publication of ZA200203536B publication Critical patent/ZA200203536B/en

Links

239000003098 androgen Substances 0.000 title claims description 19
229940030486 androgens Drugs 0.000 title description 9
150000001875 compounds Chemical class 0.000 claims description 55
238000000034 method Methods 0.000 claims description 35
125000000217 alkyl group Chemical group 0.000 claims description 33
239000000203 mixture Substances 0.000 claims description 33
229910052739 hydrogen Inorganic materials 0.000 claims description 32
239000001257 hydrogen Substances 0.000 claims description 30
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
150000002431 hydrogen Chemical class 0.000 claims description 13
125000002252 acyl group Chemical group 0.000 claims description 11
230000001548 androgenic effect Effects 0.000 claims description 11
229910052736 halogen Inorganic materials 0.000 claims description 11
150000002367 halogens Chemical group 0.000 claims description 11
125000003545 alkoxy group Chemical group 0.000 claims description 10
125000003342 alkenyl group Chemical group 0.000 claims description 9
125000000304 alkynyl group Chemical group 0.000 claims description 7
125000001424 substituent group Chemical group 0.000 claims description 6
125000000753 cycloalkyl group Chemical group 0.000 claims description 4
150000001993 dienes Chemical class 0.000 claims description 4
239000003814 drug Substances 0.000 claims description 4
238000004519 manufacturing process Methods 0.000 claims description 4
125000000392 cycloalkenyl group Chemical group 0.000 claims description 3
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
239000000126 substance Substances 0.000 claims 6
SOSBFKZJMQYDIJ-JKEDJMADSA-N (8r,9s,10r,13r,14r)-13-methyl-15-methylidene-1,2,6,7,8,9,10,11,12,14,16,17-dodecahydrocyclopenta[a]phenanthren-3-one Chemical compound C1CC2=CC(=O)CC[C@@H]2[C@@H]2[C@@H]1[C@@H]1C(=C)CC[C@@]1(C)CC2 SOSBFKZJMQYDIJ-JKEDJMADSA-N 0.000 claims 1
230000003054 hormonal effect Effects 0.000 claims 1
238000002560 therapeutic procedure Methods 0.000 claims 1
239000000047 product Substances 0.000 description 73
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 69
239000000243 solution Substances 0.000 description 35
OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 26
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 25
239000007864 aqueous solution Substances 0.000 description 25
229910052938 sodium sulfate Inorganic materials 0.000 description 25
235000011152 sodium sulphate Nutrition 0.000 description 25
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
239000012267 brine Substances 0.000 description 24
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 24
239000012074 organic phase Substances 0.000 description 23
239000011541 reaction mixture Substances 0.000 description 23
238000006243 chemical reaction Methods 0.000 description 22
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
229920006395 saturated elastomer Polymers 0.000 description 21
150000003431 steroids Chemical group 0.000 description 21
238000003756 stirring Methods 0.000 description 21
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 20
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
-1 steroid compounds Chemical class 0.000 description 17
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 16
125000004432 carbon atom Chemical group C* 0.000 description 16
238000000746 purification Methods 0.000 description 14
238000004440 column chromatography Methods 0.000 description 13
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 12
235000019270 ammonium chloride Nutrition 0.000 description 10
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
238000006722 reduction reaction Methods 0.000 description 9
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
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 8
229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
235000017557 sodium bicarbonate Nutrition 0.000 description 8
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 7
238000006027 Birch reduction reaction Methods 0.000 description 7
239000000583 progesterone congener Substances 0.000 description 7
238000010992 reflux Methods 0.000 description 7
150000003839 salts Chemical class 0.000 description 7
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 6
230000007062 hydrolysis Effects 0.000 description 6
238000006460 hydrolysis reaction Methods 0.000 description 6
239000000725 suspension Substances 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
WAHQVRCNDCHDIB-QZYSPNBYSA-N [(3s,8r,9s,10r,13s,14s,17r)-17-acetyl-17-acetyloxy-6,10,13-trimethyl-1,2,3,8,9,11,12,14,15,16-decahydrocyclopenta[a]phenanthren-3-yl] 3-cyclopentylpropanoate Chemical compound O([C@@H]1C=C2C(C)=C[C@H]3[C@@H]4CC[C@]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)(OC(=O)C)C(C)=O)C(=O)CCC1CCCC1 WAHQVRCNDCHDIB-QZYSPNBYSA-N 0.000 description 5
238000002657 hormone replacement therapy Methods 0.000 description 5
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 5
JOXIMZWYDAKGHI-UHFFFAOYSA-N p-toluenesulfonic acid Substances CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 5
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
238000001816 cooling Methods 0.000 description 4
230000000694 effects Effects 0.000 description 4
239000000706 filtrate Substances 0.000 description 4
229910052744 lithium Inorganic materials 0.000 description 4
AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 4
230000003647 oxidation Effects 0.000 description 4
238000007254 oxidation reaction Methods 0.000 description 4
VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 4
238000002360 preparation method Methods 0.000 description 4
239000007858 starting material Substances 0.000 description 4
238000003786 synthesis reaction Methods 0.000 description 4
229960003604 testosterone Drugs 0.000 description 4
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 3
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
101000775732 Homo sapiens Androgen receptor Proteins 0.000 description 3
101000928259 Homo sapiens NADPH:adrenodoxin oxidoreductase, mitochondrial Proteins 0.000 description 3
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
229910021529 ammonia Inorganic materials 0.000 description 3
229910052802 copper Inorganic materials 0.000 description 3
239000010949 copper Substances 0.000 description 3
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 3
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
229940088597 hormone Drugs 0.000 description 3
239000005556 hormone Substances 0.000 description 3
102000046818 human AR Human genes 0.000 description 3
238000005984 hydrogenation reaction Methods 0.000 description 3
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
229910052700 potassium Inorganic materials 0.000 description 3
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
239000011734 sodium Substances 0.000 description 3
229910052708 sodium Inorganic materials 0.000 description 3
RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 3
PRXNKYBFWAWBNZ-UHFFFAOYSA-N trimethylphenylammonium tribromide Chemical compound Br[Br-]Br.C[N+](C)(C)C1=CC=CC=C1 PRXNKYBFWAWBNZ-UHFFFAOYSA-N 0.000 description 3
IJOOHPMOJXWVHK-UHFFFAOYSA-N trimethylsilyl-trifluoromethansulfonate Natural products C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 3
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
206010002261 Androgen deficiency Diseases 0.000 description 2
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 2
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
241000700159 Rattus Species 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 2
239000002253 acid Substances 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
239000000654 additive Substances 0.000 description 2
230000029936 alkylation Effects 0.000 description 2
238000005804 alkylation reaction Methods 0.000 description 2
229960003473 androstanolone Drugs 0.000 description 2
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
210000004027 cell Anatomy 0.000 description 2
229910052801 chlorine Inorganic materials 0.000 description 2
239000000460 chlorine Substances 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
230000002254 contraceptive effect Effects 0.000 description 2
238000002425 crystallisation Methods 0.000 description 2
230000008025 crystallization Effects 0.000 description 2
230000002950 deficient Effects 0.000 description 2
239000002552 dosage form Substances 0.000 description 2
150000002148 esters Chemical class 0.000 description 2
229910052731 fluorine Inorganic materials 0.000 description 2
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 2
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 2
238000000338 in vitro Methods 0.000 description 2
238000001727 in vivo Methods 0.000 description 2
238000011534 incubation Methods 0.000 description 2
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
238000006317 isomerization reaction Methods 0.000 description 2
BWHLPLXXIDYSNW-UHFFFAOYSA-N ketorolac tromethamine Chemical compound OCC(N)(CO)CO.OC(=O)C1CCN2C1=CC=C2C(=O)C1=CC=CC=C1 BWHLPLXXIDYSNW-UHFFFAOYSA-N 0.000 description 2
239000007788 liquid Substances 0.000 description 2
DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 2
MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
NPAGDVCDWIYMMC-IZPLOLCNSA-N nandrolone Chemical compound O=C1CC[C@@H]2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 NPAGDVCDWIYMMC-IZPLOLCNSA-N 0.000 description 2
229960004719 nandrolone Drugs 0.000 description 2
230000007935 neutral effect Effects 0.000 description 2
125000002524 organometallic group Chemical group 0.000 description 2
239000008194 pharmaceutical composition Substances 0.000 description 2
229960005235 piperonyl butoxide Drugs 0.000 description 2
239000011591 potassium Substances 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
XXQBEVHPUKOQEO-UHFFFAOYSA-N potassium superoxide Chemical compound [K+].[K+].[O-][O-] XXQBEVHPUKOQEO-UHFFFAOYSA-N 0.000 description 2
AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 2
235000019345 sodium thiosulphate Nutrition 0.000 description 2
238000010561 standard procedure Methods 0.000 description 2
239000003826 tablet Substances 0.000 description 2
CFOAUYCPAUGDFF-UHFFFAOYSA-N tosmic Chemical compound CC1=CC=C(S(=O)(=O)C[N+]#[C-])C=C1 CFOAUYCPAUGDFF-UHFFFAOYSA-N 0.000 description 2
230000009466 transformation Effects 0.000 description 2
VFJYIHQDILEQNR-UHFFFAOYSA-M trimethylsulfanium;iodide Chemical compound [I-].C[S+](C)C VFJYIHQDILEQNR-UHFFFAOYSA-M 0.000 description 2
ZFYIQPIHXRFFCZ-QMMMGPOBSA-N (2s)-2-(cyclohexylamino)butanedioic acid Chemical compound OC(=O)C[C@@H](C(O)=O)NC1CCCCC1 ZFYIQPIHXRFFCZ-QMMMGPOBSA-N 0.000 description 1
YSGQGNQWBLYHPE-CFUSNLFHSA-N (7r,8r,9s,10r,13s,14s,17s)-17-hydroxy-7,13-dimethyl-2,6,7,8,9,10,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-3-one Chemical compound C1C[C@]2(C)[C@@H](O)CC[C@H]2[C@@H]2[C@H](C)CC3=CC(=O)CC[C@@H]3[C@H]21 YSGQGNQWBLYHPE-CFUSNLFHSA-N 0.000 description 1
FIPMUSSNRJGXLB-AIUWVKHHSA-N (7r,8r,9s,13s,14s)-13-ethyl-3-methoxy-7-methyl-7,8,9,11,12,14,15,16-octahydro-6h-cyclopenta[a]phenanthren-17-one Chemical compound COC1=CC=C2[C@H]3CC[C@](CC)(C(CC4)=O)[C@@H]4[C@@H]3[C@H](C)CC2=C1 FIPMUSSNRJGXLB-AIUWVKHHSA-N 0.000 description 1
LDMHWUXKXZSPRY-AIUWVKHHSA-N (7r,8r,9s,13s,14s)-7-ethyl-3-methoxy-13-methyl-7,8,9,11,12,14,15,16-octahydro-6h-cyclopenta[a]phenanthren-17-one Chemical compound C1C[C@]2(C)C(=O)CC[C@H]2[C@@H]2[C@H](CC)CC3=CC(OC)=CC=C3[C@H]21 LDMHWUXKXZSPRY-AIUWVKHHSA-N 0.000 description 1
DSQKVBHOMCPPKA-AIUWVKHHSA-N (7s,8r,9s,13s,14s)-7-ethenyl-3-methoxy-13-methyl-7,8,9,11,12,14,15,16-octahydro-6h-cyclopenta[a]phenanthren-17-one Chemical compound C1C[C@]2(C)C(=O)CC[C@H]2[C@@H]2[C@H](C=C)CC3=CC(OC)=CC=C3[C@H]21 DSQKVBHOMCPPKA-AIUWVKHHSA-N 0.000 description 1
SBLHOJQRZNGHLQ-ATIFRJIPSA-N (8r,9s,10r,13s,14s)-13-ethyl-1,2,6,7,8,9,10,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthrene-3,17-dione Chemical compound O=C1CC[C@@H]2[C@H]3CC[C@](CC)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 SBLHOJQRZNGHLQ-ATIFRJIPSA-N 0.000 description 1
UYKOCSIVSNFRPZ-QXUSFIETSA-N (8r,9s,10r,13s,14s)-13-methyl-1,2,6,7,8,9,10,14,15,16-decahydrocyclopenta[a]phenanthrene-3,17-dione Chemical compound O=C1CC[C@@H]2[C@H]3C=C[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 UYKOCSIVSNFRPZ-QXUSFIETSA-N 0.000 description 1
JVNDFEUKXWPZNH-BDXSIMOUSA-N (8s,9s,13s,14s)-13-methyl-1,4,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthrene Chemical compound C([C@H]1[C@@H]2CCC[C@]2(CC[C@@H]11)C)CC2=C1CC=CC2 JVNDFEUKXWPZNH-BDXSIMOUSA-N 0.000 description 1
PTBPARHSFXLKAX-AKHDSKFASA-N (8s,9s,13s,14s)-13-methyl-17-methylidene-7,8,9,11,12,14,15,16-octahydro-6h-cyclopenta[a]phenanthrene Chemical class C1=CC=C2[C@H]3CC[C@](C)(C(CC4)=C)[C@@H]4[C@@H]3CCC2=C1 PTBPARHSFXLKAX-AKHDSKFASA-N 0.000 description 1
FWYXCSGNRCNWEJ-YRXWBPOGSA-N (8s,9s,13s,14s)-3,3-dimethoxy-13-methyl-2,4,6,7,8,9,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthrene Chemical class C1C[C@@H]2C(CCC(C3)(OC)OC)=C3CC[C@H]2[C@@H]2CCC[C@]21C FWYXCSGNRCNWEJ-YRXWBPOGSA-N 0.000 description 1
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 description 1
YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 1
AAYWIXGLVAEPTP-UHFFFAOYSA-N 2,3-dimethylbutan-2-ylboron Chemical compound [B]C(C)(C)C(C)C AAYWIXGLVAEPTP-UHFFFAOYSA-N 0.000 description 1
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
AMKGKYQBASDDJB-UHFFFAOYSA-N 9$l^{2}-borabicyclo[3.3.1]nonane Chemical compound C1CCC2CCCC1[B]2 AMKGKYQBASDDJB-UHFFFAOYSA-N 0.000 description 1
FEJUGLKDZJDVFY-UHFFFAOYSA-N 9-borabicyclo[3.3.1]nonane Substances C1CCC2CCCC1B2 FEJUGLKDZJDVFY-UHFFFAOYSA-N 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
206010006187 Breast cancer Diseases 0.000 description 1
208000026310 Breast neoplasm Diseases 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
229910021589 Copper(I) bromide Inorganic materials 0.000 description 1
229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
241000699802 Cricetulus griseus Species 0.000 description 1
PMPVIKIVABFJJI-UHFFFAOYSA-N Cyclobutane Chemical compound C1CCC1 PMPVIKIVABFJJI-UHFFFAOYSA-N 0.000 description 1
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical compound C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 0.000 description 1
201000009273 Endometriosis Diseases 0.000 description 1
PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
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239000003810 Jones reagent Substances 0.000 description 1
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
229910010082 LiAlH Inorganic materials 0.000 description 1
108060001084 Luciferase Proteins 0.000 description 1
239000012359 Methanesulfonyl chloride Substances 0.000 description 1
238000006751 Mitsunobu reaction Methods 0.000 description 1
241000713333 Mouse mammary tumor virus Species 0.000 description 1
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102000016979 Other receptors Human genes 0.000 description 1
238000003527 Peterson olefination reaction Methods 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
239000007868 Raney catalyst Substances 0.000 description 1
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
229910000564 Raney nickel Inorganic materials 0.000 description 1
229920002472 Starch Chemical class 0.000 description 1
238000007239 Wittig reaction Methods 0.000 description 1
CTKRVAUZGUYITM-SXXASDTRSA-N [(8s,9s,13s,14s,17r)-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-17-yl]methanol Chemical class C1=CC=C2[C@H]3CC[C@](C)([C@@H](CC4)CO)[C@@H]4[C@@H]3CCC2=C1 CTKRVAUZGUYITM-SXXASDTRSA-N 0.000 description 1
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
230000000996 additive effect Effects 0.000 description 1
230000032683 aging Effects 0.000 description 1
238000007083 alkoxycarbonylation reaction Methods 0.000 description 1
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
230000001195 anabolic effect Effects 0.000 description 1
239000012491 analyte Substances 0.000 description 1
102000001307 androgen receptors Human genes 0.000 description 1
108010080146 androgen receptors Proteins 0.000 description 1
238000009165 androgen replacement therapy Methods 0.000 description 1
239000008346 aqueous phase Substances 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
230000004071 biological effect Effects 0.000 description 1
SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
244000309464 bull Species 0.000 description 1
125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000002775 capsule Substances 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
239000000969 carrier Substances 0.000 description 1
239000001913 cellulose Chemical class 0.000 description 1
229920002678 cellulose Chemical class 0.000 description 1
239000003638 chemical reducing agent Substances 0.000 description 1
210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
239000003086 colorant Substances 0.000 description 1
238000002648 combination therapy Methods 0.000 description 1
238000009833 condensation Methods 0.000 description 1
230000005494 condensation Effects 0.000 description 1
238000010276 construction Methods 0.000 description 1
239000003433 contraceptive agent Substances 0.000 description 1
229940124558 contraceptive agent Drugs 0.000 description 1
239000013256 coordination polymer Substances 0.000 description 1
XTVVROIMIGLXTD-UHFFFAOYSA-N copper(II) nitrate trihydrate Substances [Cu+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O XTVVROIMIGLXTD-UHFFFAOYSA-N 0.000 description 1
NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 description 1
LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
239000012043 crude product Substances 0.000 description 1
125000004093 cyano group Chemical group *C#N 0.000 description 1
150000001925 cycloalkenes Chemical group 0.000 description 1
230000001086 cytosolic effect Effects 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
150000001991 dicarboxylic acids Chemical class 0.000 description 1
HQWPLXHWEZZGKY-UHFFFAOYSA-N diethylzinc Chemical compound CC[Zn]CC HQWPLXHWEZZGKY-UHFFFAOYSA-N 0.000 description 1
NZZFYRREKKOMAT-UHFFFAOYSA-N diiodomethane Chemical compound ICI NZZFYRREKKOMAT-UHFFFAOYSA-N 0.000 description 1
229940043279 diisopropylamine Drugs 0.000 description 1
HXJFQNUWPUICNY-UHFFFAOYSA-N disiamylborane Chemical compound CC(C)C(C)BC(C)C(C)C HXJFQNUWPUICNY-UHFFFAOYSA-N 0.000 description 1
125000004119 disulfanediyl group Chemical group *SS* 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
230000008030 elimination Effects 0.000 description 1
238000003379 elimination reaction Methods 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
150000002084 enol ethers Chemical class 0.000 description 1
238000006345 epimerization reaction Methods 0.000 description 1
238000006735 epoxidation reaction Methods 0.000 description 1
229930182833 estradiol Natural products 0.000 description 1
229960005309 estradiol Drugs 0.000 description 1
BLHLJVCOVBYQQS-UHFFFAOYSA-N ethyllithium Chemical compound [Li]CC BLHLJVCOVBYQQS-UHFFFAOYSA-N 0.000 description 1
125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
239000000945 filler Substances 0.000 description 1
238000001914 filtration Methods 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 1
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 description 1
125000003707 hexyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
238000001794 hormone therapy Methods 0.000 description 1
238000006197 hydroboration reaction Methods 0.000 description 1
239000005457 ice water Substances 0.000 description 1
239000007943 implant Substances 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
239000011630 iodine Substances 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
229960004592 isopropanol Drugs 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000008101 lactose Substances 0.000 description 1
239000012280 lithium aluminium hydride Substances 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
210000005001 male reproductive tract Anatomy 0.000 description 1
HZVOZRGWRWCICA-UHFFFAOYSA-N methanediyl Chemical compound [CH2] HZVOZRGWRWCICA-UHFFFAOYSA-N 0.000 description 1
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 1
239000011707 mineral Substances 0.000 description 1
235000010755 mineral Nutrition 0.000 description 1
210000003205 muscle Anatomy 0.000 description 1
230000001016 myotrophic effect Effects 0.000 description 1
239000007922 nasal spray Substances 0.000 description 1
229940097496 nasal spray Drugs 0.000 description 1
239000012038 nucleophile Substances 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
238000006053 organic reaction Methods 0.000 description 1
210000001672 ovary Anatomy 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
150000004965 peroxy acids Chemical class 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
PWXJULSLLONQHY-UHFFFAOYSA-N phenylcarbamic acid Chemical compound OC(=O)NC1=CC=CC=C1 PWXJULSLLONQHY-UHFFFAOYSA-N 0.000 description 1
125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
239000006187 pill Substances 0.000 description 1
XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
239000002243 precursor Substances 0.000 description 1
239000000651 prodrug Substances 0.000 description 1
229940002612 prodrug Drugs 0.000 description 1
230000000757 progestagenic effect Effects 0.000 description 1
125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
210000002307 prostate Anatomy 0.000 description 1
ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 1
102000005962 receptors Human genes 0.000 description 1
108020003175 receptors Proteins 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
239000007787 solid Substances 0.000 description 1
239000007921 spray Substances 0.000 description 1
239000008107 starch Chemical class 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
230000000707 stereoselective effect Effects 0.000 description 1
239000003270 steroid hormone Substances 0.000 description 1
239000013589 supplement Substances 0.000 description 1
230000009469 supplementation Effects 0.000 description 1
239000000829 suppository Substances 0.000 description 1
230000001629 suppression Effects 0.000 description 1
238000013268 sustained release Methods 0.000 description 1
239000012730 sustained-release form Substances 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
238000000844 transformation Methods 0.000 description 1
GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
210000004881 tumor cell Anatomy 0.000 description 1
229940044953 vaginal ring Drugs 0.000 description 1
239000006213 vaginal ring Substances 0.000 description 1
125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1
PGOLTJPQCISRTO-UHFFFAOYSA-N vinyllithium Chemical compound [Li]C=C PGOLTJPQCISRTO-UHFFFAOYSA-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
- C07J53/002—Carbocyclic rings fused
- C07J53/004—3 membered carbocyclic rings
- 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
- A61P15/16—Masculine 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
- A61P5/26—Androgens
- 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
- A61P5/28—Antiandrogens

Landscapes

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

ZA200203536A 1999-12-02 2002-05-03 14,15-beta-methylene substituted androgens. ZA200203536B (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
EP99204080		1999-12-02

Publications (1)

Publication Number	Publication Date
ZA200203536B true ZA200203536B (en)	2003-08-04

Family

ID=8240955

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
ZA200203536A ZA200203536B (en)	1999-12-02	2002-05-03	14,15-beta-methylene substituted androgens.

Country Status (27)

Country	Link
US (1)	US6706700B2 (fr)
EP (1)	EP1237904B1 (fr)
JP (1)	JP2003515543A (fr)
CN (1)	CN1166680C (fr)
AR (1)	AR026655A1 (fr)
AT (1)	ATE317396T1 (fr)
AU (1)	AU778017B2 (fr)
CA (1)	CA2390226A1 (fr)
CO (1)	CO5251441A1 (fr)
CY (1)	CY1106086T1 (fr)
CZ (1)	CZ301376B6 (fr)
DE (1)	DE60025958T2 (fr)
DK (1)	DK1237904T3 (fr)
ES (1)	ES2258037T3 (fr)
HK (1)	HK1047596B (fr)
HU (1)	HUP0203611A3 (fr)
IL (1)	IL149424A (fr)
MX (1)	MXPA02004939A (fr)
NO (1)	NO322422B1 (fr)
NZ (1)	NZ518753A (fr)
PE (1)	PE20011033A1 (fr)
PL (1)	PL202999B1 (fr)
RU (1)	RU2242479C2 (fr)
SK (1)	SK287095B6 (fr)
TW (1)	TWI275593B (fr)
WO (1)	WO2001040255A2 (fr)
ZA (1)	ZA200203536B (fr)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
ES2204613T3 (es) *	1999-04-06	2004-05-01	Akzo Nobel N.V.	Androgenos 7-alfa alquilo oralmente activos.
EP1470151B1 (fr) *	2002-01-21	2009-12-30	N.V. Organon	Procede de preparation de 7-alpha-methylsteroides
US20080293683A1 (en) *	2007-05-24	2008-11-27	University Of Kansas Medical Center	Hormone Replacement Therapy
EP2383279A1 (fr)	2011-07-19	2011-11-02	Pantarhei Bioscience B.V.	Procédé de préparation d'estetrol
WO2013050553A1 (fr) *	2011-10-07	2013-04-11	Estetra S.A.	Procédé de production d'estétrol
JP6866561B2 (ja)	2015-06-18	2021-04-28	エステトラソシエテプリーヴアレスポンサビリテリミテ	エステトロールを含有する口腔内崩壊錠
SI3701944T1 (sl)	2015-06-18	2022-04-29	Estetra Srl	Orodisperzibilna odmerna enota, ki vsebuje estetrolno komponento
CR20180042A (es)	2015-06-18	2018-05-03	Mithra Pharmaceuticals S A	Unidad de dosificación orodispersable que contiene un componente estetrol.
SI3310346T1 (sl)	2015-06-18	2021-07-30	Estetra Sprl	Orodisperzibilna tableta, ki vsebuje estetrol
KR102712911B1 (ko)	2016-08-05	2024-10-04	에스테트라, 소시에떼 아 레스폰서빌리떼 리미떼	월경통 및 생리통의 관리방법
JOP20200260A1 (ar)	2018-04-19	2019-10-19	Estetra Sprl	مركبات واستخداماتها للتخفيف من الأعراض المصاحبة لانقطاع الطمث
TWI801561B (zh)	2018-04-19	2023-05-11	比利時商依思特拉私人有限責任公司	化合物及其用於緩解絕經相關症狀的用途
CN111621141B (zh) *	2020-06-12	2022-04-08	广西大学	一种缓释型二氧化氯-水性聚氨酯抗菌膜及其制备方法

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3086027A (en) *	1960-01-22	1963-04-16	Lilly Co Eli	19-nor-4, 9(10)-steroids and process
IE60780B1 (en)	1987-01-23	1994-08-10	Akzo Nv	New 11-aryl steroid derivatives
DE19537626A1 (de)	1995-10-10	1997-04-17	Jenapharm Gmbh	Steroide mit einer 14, 15-Methylengruppe
DE19827522A1 (de) *	1998-06-22	1999-12-23	Jenapharm Gmbh	14,15-Cyclopropanosteroide der 19-Nor-Androstanreihe, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende pharmazeutische Präparate
WO2000053619A1 (fr) *	1999-03-08	2000-09-14	Akzo Nobel N.V.	Derives de 14.beta., alpha-hydroxymethylandrostane intervenant comme androgenes

2000
- 2000-11-29 HU HU0203611A patent/HUP0203611A3/hu unknown
- 2000-11-29 CZ CZ20021894A patent/CZ301376B6/cs not_active IP Right Cessation
- 2000-11-29 DE DE60025958T patent/DE60025958T2/de not_active Expired - Lifetime
- 2000-11-29 EP EP00993259A patent/EP1237904B1/fr not_active Expired - Lifetime
- 2000-11-29 AT AT00993259T patent/ATE317396T1/de not_active IP Right Cessation
- 2000-11-29 AU AU28383/01A patent/AU778017B2/en not_active Ceased
- 2000-11-29 RU RU2002117440/04A patent/RU2242479C2/ru not_active IP Right Cessation
- 2000-11-29 JP JP2001541010A patent/JP2003515543A/ja active Pending
- 2000-11-29 SK SK758-2002A patent/SK287095B6/sk not_active IP Right Cessation
- 2000-11-29 MX MXPA02004939A patent/MXPA02004939A/es active IP Right Grant
- 2000-11-29 US US10/148,820 patent/US6706700B2/en not_active Expired - Fee Related
- 2000-11-29 IL IL149424A patent/IL149424A/en not_active IP Right Cessation
- 2000-11-29 PL PL355689A patent/PL202999B1/pl not_active IP Right Cessation
- 2000-11-29 CA CA002390226A patent/CA2390226A1/fr not_active Abandoned
- 2000-11-29 DK DK00993259T patent/DK1237904T3/da active
- 2000-11-29 NZ NZ518753A patent/NZ518753A/en unknown
- 2000-11-29 ES ES00993259T patent/ES2258037T3/es not_active Expired - Lifetime
- 2000-11-29 WO PCT/EP2000/012009 patent/WO2001040255A2/fr active IP Right Grant
- 2000-11-29 CN CNB008164959A patent/CN1166680C/zh not_active Expired - Fee Related
- 2000-11-30 AR ARP000106304A patent/AR026655A1/es active IP Right Grant
- 2000-12-01 PE PE2000001285A patent/PE20011033A1/es not_active Application Discontinuation
- 2000-12-01 CO CO00092012A patent/CO5251441A1/es not_active Application Discontinuation
- 2000-12-02 TW TW089125707A patent/TWI275593B/zh not_active IP Right Cessation
2002
- 2002-05-03 ZA ZA200203536A patent/ZA200203536B/en unknown
- 2002-05-30 NO NO20022564A patent/NO322422B1/no not_active IP Right Cessation
- 2002-12-18 HK HK02109169.4A patent/HK1047596B/zh not_active IP Right Cessation
2006
- 2006-04-10 CY CY20061100500T patent/CY1106086T1/el unknown

Also Published As

Publication number	Publication date
ATE317396T1 (de)	2006-02-15
PE20011033A1 (es)	2001-10-11
CO5251441A1 (es)	2003-02-28
AU778017B2 (en)	2004-11-11
CN1166680C (zh)	2004-09-15
EP1237904B1 (fr)	2006-02-08
HK1047596A1 (en)	2003-02-28
HK1047596B (zh)	2006-04-21
MXPA02004939A (es)	2003-05-23
SK7582002A3 (en)	2002-09-10
CZ301376B6 (cs)	2010-02-03
TWI275593B (en)	2007-03-11
DK1237904T3 (da)	2006-06-06
AR026655A1 (es)	2003-02-19
IL149424A0 (en)	2002-11-10
US20030100543A1 (en)	2003-05-29
CY1106086T1 (el)	2011-06-08
CZ20021894A3 (cs)	2002-08-14
WO2001040255A3 (fr)	2001-11-15
DE60025958T2 (de)	2006-07-27
SK287095B6 (sk)	2009-12-07
NO20022564L (no)	2002-05-30
JP2003515543A (ja)	2003-05-07
IL149424A (en)	2007-05-15
PL202999B1 (pl)	2009-08-31
HUP0203611A2 (hu)	2003-03-28
CN1402735A (zh)	2003-03-12
RU2242479C2 (ru)	2004-12-20
US6706700B2 (en)	2004-03-16
DE60025958D1 (de)	2006-04-20
HUP0203611A3 (en)	2004-07-28
PL355689A1 (en)	2004-05-17
CA2390226A1 (fr)	2001-06-07
NO20022564D0 (no)	2002-05-30
NO322422B1 (no)	2006-10-02
ES2258037T3 (es)	2006-08-16
AU2838301A (en)	2001-06-12
EP1237904A2 (fr)	2002-09-11
NZ518753A (en)	2004-05-28
WO2001040255A2 (fr)	2001-06-07

Publication	Publication Date	Title
EP1237904B1 (fr)	2006-02-08	Androgenes 14,15-beta-methylene substitues
US6881728B1 (en)	2005-04-19	14-β, 17-α-hydroxymethylandrostane derivatives as androgens
KR100730010B1 (ko)	2007-06-20	신규 안드로겐
KR20100037596A (ko)	2010-04-09	17β-시아노-19-안드로스트-4-엔 유도체, 그의 용도, 및 상기 유도체를 함유하는 의약
CA2431355C (fr)	2009-11-24	Steroides du type 14.beta.,16,17-methylene tenant lieu d'androgenes
US20040059140A1 (en)	2004-03-25	14(15)-unsaturated 15- and/or 16-substituted androgens with mixed androgen-progrestational profile
AU2002224923A1 (en)	2002-08-29	Methylene steroids as novel androgens