SK712002A3 - Androgen compounds, pharmaceutical composition containing the same and a kit containing the same - Google Patents

Androgen compounds, pharmaceutical composition containing the same and a kit containing the same Download PDF

Info

Publication number: SK712002A3
Authority: SK; Slovakia
Prior art keywords: alkyl; product; solution; ethyl; ethenyl
Prior art date: 1999-07-16

Application number

SK71-2002A

Other languages

English (en)

Slovak (sk)

Inventor

Hubert Jan Jozef Loozen

Dirk Leysen

Der Louw Jaap Van

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.)

1999-07-16

Filing date

2000-07-10

Publication date

2002-06-04

2000-07-10 Application filed by Akzo Nobel Nv filed Critical Akzo Nobel Nv

2002-06-04 Publication of SK712002A3 publication Critical patent/SK712002A3/sk

Links

150000001875 compounds Chemical class 0.000 title claims abstract description 35
239000003098 androgen Substances 0.000 title claims abstract description 22
239000008194 pharmaceutical composition Substances 0.000 title claims 6
125000000217 alkyl group Chemical group 0.000 claims abstract description 29
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 25
125000002252 acyl group Chemical group 0.000 claims abstract description 16
239000001257 hydrogen Substances 0.000 claims abstract description 16
229910052736 halogen Inorganic materials 0.000 claims abstract description 11
150000002367 halogens Chemical group 0.000 claims abstract description 11
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 9
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims abstract description 9
125000000304 alkynyl group Chemical group 0.000 claims abstract description 7
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims abstract description 7
125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims abstract description 5
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 5
125000000298 cyclopropenyl group Chemical group [H]C1=C([H])C1([H])* 0.000 claims abstract description 4
-1 1,2-propadienyl Chemical group 0.000 claims description 31
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 11
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 6
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 4
125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 4
HOZITFWTDHEPCU-WKCJJHKESA-N (7r,8r,9r,10r,13s,17s)-7-ethyl-17-hydroxy-13-methyl-2,6,7,8,9,10,11,12,16,17-decahydro-1h-cyclopenta[a]phenanthren-3-one Chemical compound C1C[C@]2(C)[C@@H](O)CC=C2[C@@H]2[C@H](CC)CC3=CC(=O)CC[C@@H]3[C@H]21 HOZITFWTDHEPCU-WKCJJHKESA-N 0.000 claims description 3
125000006017 1-propenyl group Chemical group 0.000 claims description 3
125000000530 1-propynyl group Chemical group [H]C([H])([H])C#C* 0.000 claims description 3
239000003814 drug Substances 0.000 claims description 2
239000002583 male contraceptive agent Substances 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims description 2
206010002261 Androgen deficiency Diseases 0.000 claims 1
239000004480 active ingredient Substances 0.000 claims 1
239000003937 drug carrier Substances 0.000 claims 1
239000000583 progesterone congener Substances 0.000 claims 1
230000003637 steroidlike Effects 0.000 claims 1
229940030486 androgens Drugs 0.000 abstract description 9
150000002431 hydrogen Chemical group 0.000 abstract description 3
125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 1
239000000047 product Substances 0.000 description 114
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 99
239000000243 solution Substances 0.000 description 78
238000000034 method Methods 0.000 description 49
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 40
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 39
229920006395 saturated elastomer Polymers 0.000 description 37
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 36
239000000203 mixture Substances 0.000 description 35
239000011541 reaction mixture Substances 0.000 description 35
239000012267 brine Substances 0.000 description 33
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 33
239000012074 organic phase Substances 0.000 description 32
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 31
229910052938 sodium sulfate Inorganic materials 0.000 description 31
235000011152 sodium sulphate Nutrition 0.000 description 31
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 30
238000003756 stirring Methods 0.000 description 28
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 24
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
150000003431 steroids Chemical class 0.000 description 21
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
238000004440 column chromatography Methods 0.000 description 20
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 20
238000000746 purification Methods 0.000 description 19
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
229910000030 sodium bicarbonate Inorganic materials 0.000 description 18
235000017557 sodium bicarbonate Nutrition 0.000 description 18
238000006243 chemical reaction Methods 0.000 description 17
235000019270 ammonium chloride Nutrition 0.000 description 15
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 14
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
238000010992 reflux Methods 0.000 description 12
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 11
125000004122 cyclic group Chemical group 0.000 description 11
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
125000004432 carbon atom Chemical group C* 0.000 description 10
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 10
241000700159 Rattus Species 0.000 description 9
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 8
238000001816 cooling Methods 0.000 description 8
AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 8
239000000725 suspension Substances 0.000 description 8
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 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 7
229910052744 lithium Inorganic materials 0.000 description 7
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 6
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 6
230000000694 effects Effects 0.000 description 6
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
210000002966 serum Anatomy 0.000 description 6
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 5
150000000319 19-nortestosterones Chemical class 0.000 description 5
QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 5
125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 5
229910021529 ammonia Inorganic materials 0.000 description 5
230000015572 biosynthetic process Effects 0.000 description 5
239000000706 filtrate Substances 0.000 description 5
210000003494 hepatocyte Anatomy 0.000 description 5
238000011534 incubation Methods 0.000 description 5
230000002503 metabolic effect Effects 0.000 description 5
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 5
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
GDDDQTOBTQTTJD-NCOADZHNSA-N (8s,9s,13s,14s)-3-methoxy-6,7,8,9,11,12,13,14,15,16-decahydrocyclopenta[a]phenanthren-17-one Chemical class C1C[C@@H]2C(=O)CC[C@H]2[C@@H]2CCC3=CC(OC)=CC=C3[C@H]21 GDDDQTOBTQTTJD-NCOADZHNSA-N 0.000 description 4
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
238000005160 1H NMR spectroscopy Methods 0.000 description 4
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
239000007864 aqueous solution Substances 0.000 description 4
IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 4
229910052943 magnesium sulfate Inorganic materials 0.000 description 4
235000019341 magnesium sulphate Nutrition 0.000 description 4
125000004043 oxo group Chemical group O=* 0.000 description 4
239000012279 sodium borohydride Substances 0.000 description 4
229910000033 sodium borohydride Inorganic materials 0.000 description 4
GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 4
125000001424 substituent group Chemical group 0.000 description 4
238000003786 synthesis reaction Methods 0.000 description 4
229960003604 testosterone Drugs 0.000 description 4
PRXNKYBFWAWBNZ-UHFFFAOYSA-N trimethylphenylammonium tribromide Chemical compound Br[Br-]Br.C[N+](C)(C)C1=CC=CC=C1 PRXNKYBFWAWBNZ-UHFFFAOYSA-N 0.000 description 4
125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
238000006027 Birch reduction reaction Methods 0.000 description 3
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 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
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
238000003556 assay Methods 0.000 description 3
239000003153 chemical reaction reagent Substances 0.000 description 3
229910052802 copper Inorganic materials 0.000 description 3
239000010949 copper Substances 0.000 description 3
239000012043 crude product Substances 0.000 description 3
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
150000002148 esters Chemical class 0.000 description 3
125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 3
229910052731 fluorine Inorganic materials 0.000 description 3
239000011737 fluorine Substances 0.000 description 3
238000006317 isomerization reaction Methods 0.000 description 3
229910052708 sodium Inorganic materials 0.000 description 3
239000011734 sodium Substances 0.000 description 3
AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 3
235000019345 sodium thiosulphate Nutrition 0.000 description 3
239000007787 solid Substances 0.000 description 3
238000010561 standard procedure Methods 0.000 description 3
239000000126 substance Substances 0.000 description 3
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
SZUQEFSFJHBUTH-AKSHTRIKSA-N (7r,8r,9s,13s,14s)-7,13-diethyl-3-methoxy-7,8,9,11,12,14,15,16-octahydro-6h-cyclopenta[a]phenanthren-17-one Chemical compound C1C[C@]2(CC)C(=O)CC[C@H]2[C@@H]2[C@H](CC)CC3=CC(OC)=CC=C3[C@H]21 SZUQEFSFJHBUTH-AKSHTRIKSA-N 0.000 description 2
OZNBHKWBLFJMQJ-LHHMISFZSA-N (8R,9R,10R,13R)-13-methyl-2,6,7,8,9,10,11,12,16,17-decahydro-1H-cyclopenta[a]phenanthren-3-one Chemical compound C1CC2=CC(=O)CC[C@@H]2[C@@H]2[C@@H]1C1=CCC[C@@]1(C)CC2 OZNBHKWBLFJMQJ-LHHMISFZSA-N 0.000 description 2
AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 2
AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 2
YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 2
GGCQFPGJIWPKBF-FTAFEQPUSA-N 3-[(7r,8r,9s,13s,14s)-3-methoxy-13-methyl-17-oxo-7,8,9,11,12,14,15,16-octahydro-6h-cyclopenta[a]phenanthren-7-yl]propyl acetate Chemical compound C1C[C@]2(C)C(=O)CC[C@H]2[C@@H]2[C@H](CCCOC(C)=O)CC3=CC(OC)=CC=C3[C@H]21 GGCQFPGJIWPKBF-FTAFEQPUSA-N 0.000 description 2
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
229910021595 Copper(I) iodide Inorganic materials 0.000 description 2
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-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
HETCEOQFVDFGSY-UHFFFAOYSA-N Isopropenyl acetate Chemical compound CC(=C)OC(C)=O HETCEOQFVDFGSY-UHFFFAOYSA-N 0.000 description 2
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
239000002253 acid Substances 0.000 description 2
125000003342 alkenyl group Chemical group 0.000 description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
229910052794 bromium Inorganic materials 0.000 description 2
ODWXUNBKCRECNW-UHFFFAOYSA-M bromocopper(1+) Chemical compound Br[Cu+] ODWXUNBKCRECNW-UHFFFAOYSA-M 0.000 description 2
244000309464 bull Species 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
210000004027 cell Anatomy 0.000 description 2
239000003638 chemical reducing agent Substances 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
239000000460 chlorine Substances 0.000 description 2
229910052801 chlorine Inorganic materials 0.000 description 2
238000004140 cleaning Methods 0.000 description 2
229940116318 copper carbonate Drugs 0.000 description 2
LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 2
GEZOTWYUIKXWOA-UHFFFAOYSA-L copper;carbonate Chemical compound [Cu+2].[O-]C([O-])=O GEZOTWYUIKXWOA-UHFFFAOYSA-L 0.000 description 2
238000002425 crystallisation Methods 0.000 description 2
230000008025 crystallization Effects 0.000 description 2
230000007812 deficiency Effects 0.000 description 2
230000001605 fetal effect Effects 0.000 description 2
238000001914 filtration Methods 0.000 description 2
239000008187 granular material Substances 0.000 description 2
229940088597 hormone Drugs 0.000 description 2
239000005556 hormone Substances 0.000 description 2
230000007062 hydrolysis Effects 0.000 description 2
238000006460 hydrolysis reaction Methods 0.000 description 2
239000011630 iodine Substances 0.000 description 2
229910052740 iodine Inorganic materials 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
239000012280 lithium aluminium hydride Substances 0.000 description 2
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
229960004719 nandrolone Drugs 0.000 description 2
230000007935 neutral effect Effects 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
239000012044 organic layer Substances 0.000 description 2
238000007254 oxidation reaction Methods 0.000 description 2
239000012071 phase Substances 0.000 description 2
239000006187 pill 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
230000003389 potentiating effect Effects 0.000 description 2
239000002243 precursor Substances 0.000 description 2
238000002953 preparative HPLC Methods 0.000 description 2
239000000651 prodrug Substances 0.000 description 2
229940002612 prodrug Drugs 0.000 description 2
125000006239 protecting group Chemical group 0.000 description 2
JQRYUMGHOUYJFW-UHFFFAOYSA-N pyridine;trihydrobromide Chemical compound [Br-].[Br-].[Br-].C1=CC=[NH+]C=C1.C1=CC=[NH+]C=C1.C1=CC=[NH+]C=C1 JQRYUMGHOUYJFW-UHFFFAOYSA-N 0.000 description 2
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 2
239000000377 silicon dioxide Substances 0.000 description 2
235000010265 sodium sulphite Nutrition 0.000 description 2
239000007858 starting material Substances 0.000 description 2
125000001412 tetrahydropyranyl group Chemical group 0.000 description 2
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125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
230000002381 testicular Effects 0.000 description 1
UGNWTBMOAKPKBL-UHFFFAOYSA-N tetrachloro-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(Cl)=C(Cl)C1=O UGNWTBMOAKPKBL-UHFFFAOYSA-N 0.000 description 1
229910052723 transition metal Inorganic materials 0.000 description 1
150000003624 transition metals Chemical class 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
210000003462 vein Anatomy 0.000 description 1
230000035899 viability Effects 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1
239000008096 xylene Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
- C07J1/0051—Estrane derivatives
- C07J1/0066—Estrane derivatives substituted in position 17 beta not substituted in position 17 alfa
- C07J1/007—Estrane derivatives substituted in position 17 beta not substituted in position 17 alfa the substituent being an OH group free esterified or etherified
- C07J1/0074—Esters
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
- C07J1/0051—Estrane derivatives
- C07J1/0066—Estrane derivatives substituted in position 17 beta not substituted in position 17 alfa
- C07J1/007—Estrane derivatives substituted in position 17 beta not substituted in position 17 alfa the substituent being an OH group free esterified or etherified

Landscapes

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

SK71-2002A 1999-07-16 2000-07-10 Androgen compounds, pharmaceutical composition containing the same and a kit containing the same SK712002A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
EP99202348		1999-07-16
PCT/EP2000/006544 WO2001005806A1 (en)	1999-07-16	2000-07-10	Orally active androgens

Publications (1)

Publication Number	Publication Date
SK712002A3 true SK712002A3 (en)	2002-06-04

Family

ID=8240463

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK71-2002A SK712002A3 (en)	1999-07-16	2000-07-10	Androgen compounds, pharmaceutical composition containing the same and a kit containing the same

Country Status (28)

Country	Link
US (3)	US6313108B1 (cs)
EP (1)	EP1203011B1 (cs)
JP (1)	JP2003505394A (cs)
KR (1)	KR20020092890A (cs)
CN (1)	CN1360589A (cs)
AR (1)	AR024746A1 (cs)
AT (1)	ATE257159T1 (cs)
AU (1)	AU770412B2 (cs)
BR (1)	BR0012489A (cs)
CA (1)	CA2379223A1 (cs)
CO (1)	CO5200765A1 (cs)
CZ (1)	CZ2002192A3 (cs)
DE (1)	DE60007530T2 (cs)
ES (1)	ES2213596T3 (cs)
HK (1)	HK1043797A1 (cs)
HU (1)	HUP0201952A3 (cs)
IL (1)	IL147332A0 (cs)
MX (1)	MXPA02000601A (cs)
NO (1)	NO20020222L (cs)
NZ (1)	NZ516525A (cs)
PE (1)	PE20010330A1 (cs)
PL (1)	PL353007A1 (cs)
RU (1)	RU2002103883A (cs)
SK (1)	SK712002A3 (cs)
TR (1)	TR200200076T2 (cs)
TW (1)	TW548277B (cs)
WO (1)	WO2001005806A1 (cs)
ZA (1)	ZA200200106B (cs)

Families Citing this family (24)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US6756366B1 (en) *	1999-04-06	2004-06-29	Akzo Nobel N.V.	Orally active androgens
CA2402524C (en) *	2000-03-31	2009-11-17	Richard P. Blye	Methods of making and using 7.alpha.,11.beta.-dimethyl-17.beta.-hydroxy-4-estren-3-one 17.beta.-trans-4-n-butylcyclohexane carboxylate and 7.alpha.,11.beta.-dimethyl-17.beta.-hydroxyestr-4-en-3-one 17-undecanoate
US20030069215A1 (en) *	2001-03-30	2003-04-10	The Government Of The United States Of America,	Methods of making and using 7a,11b-dimethyl-17b-hydroxy-4-estren-3-one 17b-trans-4-n-butylcyclohexane carboxylate and 7a,11b-dimethyl-17b-hydroxyestr-4-en-3-one 17-undecanoate
HRP20030060A2 (en) *	2000-07-28	2004-06-30	Akzo Nobel Nv	16alpha-methyl or ethyl substituted estrogens
DK1379253T3 (da) *	2001-03-30	2006-06-26	Us Gov Health & Human Serv	Fremgangsmåde til fremstilling og anvendelse af farmaceutiske formuleringer omfattende 7alfa, 11beta-dimethyl-17beta-hydroxyestra-4, 14-dien-3-on og 17-estere heraf
ATE453659T1 (de) *	2002-01-21	2010-01-15	Organon Nv	Verfahren zur herstellung von 7-alpha- methylsteroide
GB0304927D0 (en) *	2003-03-04	2003-04-09	Resolution Chemicals Ltd	Process for the production of tibolone
PE20050677A1 (es)	2003-12-22	2005-10-04	Akzo Nobel Nv	Esteroides con perfil androgenico y progestagenico mixto
UA89964C2 (ru)	2004-09-08	2010-03-25	Н.В. Органон	15β-ЗАМЕЩЕННЫЕ СТЕРОИДЫ, КОТОРЫЕ ИМЕЮТ СЕЛЕКТИВНУЮ ЭСТРОГЕННУЮ АКТИВНОСТЬ
WO2010043404A1 (en) *	2008-10-15	2010-04-22	Synthon B.V.	Processes and intermediates for the production of fulvestrant
WO2012164096A1 (en)	2011-06-01	2012-12-06	Estetra S.A.	Process for the production of estetrol intermediates
BR112013030833B1 (pt) *	2011-06-01	2019-09-03	Estetra S A	processo para a preparação de um composto de fórmula (i) e processo para a preparação de estetrol
EP2383279A1 (en)	2011-07-19	2011-11-02	Pantarhei Bioscience B.V.	Process for the preparation of estetrol
EP2764008B1 (en) *	2011-10-07	2016-08-17	Estetra S.P.R.L.	Process for the production of estetrol
WO2015181116A1 (en)	2014-05-26	2015-12-03	Crystal Pharma, S.A.U.	Process and intermediades for the preparation of 7-alkylated steroids
RS57328B1 (sr)	2015-06-18	2018-08-31	Mithra Pharmaceuticals S A	Orodisperzibilna dozna jedinica koja sadrži estetrolsku komponentu
WO2016203044A1 (en)	2015-06-18	2016-12-22	Mithra Pharmaceuticals S.A.	Orodispersible tablet containing estetrol
LT3310345T (lt)	2015-06-18	2021-06-25	Estetra Sprl	Burnoje disperguojama tabletė, turinti estetrolio
NZ737945A (en)	2015-06-18	2023-06-30	Estetra Sprl	Orodispersible dosage unit containing an estetrol component
CA3178291A1 (en)	2016-08-05	2018-04-12	Estetra Srl	Method for the management of dysmenorrhea and menstrual pain
ES2906117T3 (es) *	2017-02-23	2022-04-13	Siemens Healthcare Diagnostics Inc	Conjugados de androstenodiona quimioluminiscente
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
CR20200486A (es)	2018-04-19	2021-01-27	Estetra Sprl	Compuestos y sus usos para aliviar los síntomas asociados a la menopausa
TWI893101B (zh)	2020-04-16	2025-08-11	比利時商埃斯特拉有限責任公司	具有降低之副作用之避孕組成物

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
ZA712312B (en) *	1970-04-28	1972-01-26	Ochsner Med Found Alton	4,14-estradiene compounds

2000
- 2000-06-27 TW TW089112646A patent/TW548277B/zh not_active IP Right Cessation
- 2000-07-10 PL PL00353007A patent/PL353007A1/xx not_active IP Right Cessation
- 2000-07-10 CA CA002379223A patent/CA2379223A1/en not_active Abandoned
- 2000-07-10 EP EP00953032A patent/EP1203011B1/en not_active Expired - Lifetime
- 2000-07-10 NZ NZ516525A patent/NZ516525A/xx unknown
- 2000-07-10 JP JP2001511464A patent/JP2003505394A/ja not_active Withdrawn
- 2000-07-10 CZ CZ2002192A patent/CZ2002192A3/cs unknown
- 2000-07-10 ES ES00953032T patent/ES2213596T3/es not_active Expired - Lifetime
- 2000-07-10 BR BR0012489-3A patent/BR0012489A/pt not_active IP Right Cessation
- 2000-07-10 IL IL14733200A patent/IL147332A0/xx unknown
- 2000-07-10 DE DE60007530T patent/DE60007530T2/de not_active Expired - Fee Related
- 2000-07-10 WO PCT/EP2000/006544 patent/WO2001005806A1/en not_active Ceased
- 2000-07-10 SK SK71-2002A patent/SK712002A3/sk unknown
- 2000-07-10 MX MXPA02000601A patent/MXPA02000601A/es not_active Application Discontinuation
- 2000-07-10 CN CN00810310A patent/CN1360589A/zh active Pending
- 2000-07-10 AT AT00953032T patent/ATE257159T1/de not_active IP Right Cessation
- 2000-07-10 RU RU2002103883/04A patent/RU2002103883A/ru unknown
- 2000-07-10 AU AU65629/00A patent/AU770412B2/en not_active Ceased
- 2000-07-10 TR TR2002/00076T patent/TR200200076T2/xx unknown
- 2000-07-10 HK HK02105466.2A patent/HK1043797A1/zh unknown
- 2000-07-10 HU HU0201952A patent/HUP0201952A3/hu unknown
- 2000-07-10 KR KR1020027000566A patent/KR20020092890A/ko not_active Withdrawn
- 2000-07-11 US US09/613,350 patent/US6313108B1/en not_active Expired - Fee Related
- 2000-07-13 CO CO00052876A patent/CO5200765A1/es not_active Application Discontinuation
- 2000-07-14 AR ARP000103625A patent/AR024746A1/es not_active Application Discontinuation
- 2000-07-14 PE PE2000000702A patent/PE20010330A1/es not_active Application Discontinuation
2001
- 2001-07-31 US US09/918,626 patent/US6541465B2/en not_active Expired - Fee Related
2002
- 2002-01-04 ZA ZA200200106A patent/ZA200200106B/xx unknown
- 2002-01-15 NO NO20020222A patent/NO20020222L/no not_active Application Discontinuation
- 2002-10-24 US US10/280,038 patent/US6780854B2/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
CN1360589A (zh)	2002-07-24
NO20020222L (no)	2002-01-25
US20020022609A1 (en)	2002-02-21
US6780854B2 (en)	2004-08-24
TR200200076T2 (tr)	2002-04-22
EP1203011A1 (en)	2002-05-08
AR024746A1 (es)	2002-10-23
WO2001005806A1 (en)	2001-01-25
DE60007530D1 (de)	2004-02-05
US6541465B2 (en)	2003-04-01
HK1043797A1 (zh)	2002-09-27
ATE257159T1 (de)	2004-01-15
TW548277B (en)	2003-08-21
HUP0201952A3 (en)	2003-10-28
JP2003505394A (ja)	2003-02-12
BR0012489A (pt)	2002-04-02
PE20010330A1 (es)	2001-03-22
DE60007530T2 (de)	2004-12-23
ZA200200106B (en)	2003-06-25
RU2002103883A (ru)	2004-02-27
AU770412B2 (en)	2004-02-19
EP1203011B1 (en)	2004-01-02
NO20020222D0 (no)	2002-01-15
US6313108B1 (en)	2001-11-06
CO5200765A1 (es)	2002-09-27
NZ516525A (en)	2003-06-30
MXPA02000601A (es)	2002-07-30
ES2213596T3 (es)	2004-09-01
CA2379223A1 (en)	2001-01-25
HUP0201952A2 (en)	2002-10-28
PL353007A1 (en)	2003-09-22
US20030087886A1 (en)	2003-05-08
CZ2002192A3 (cs)	2002-06-12
AU6562900A (en)	2001-02-05
IL147332A0 (en)	2002-08-14
KR20020092890A (ko)	2002-12-12

Publication	Publication Date	Title
US6313108B1 (en)	2001-11-06	Orally active androgens
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
JP2012528075A6 (ja)	2013-03-04	Ｃ−環−置換されたプレグン−４−エン−２１，１７−カルボラクトン、及びそれを含んで成る医薬製品
JP2012528075A (ja)	2012-11-12	Ｃ−環−置換されたプレグン−４−エン−２１，１７−カルボラクトン、及びそれを含んで成る医薬製品
EP1212345B1 (en)	2003-08-06	Orally active 7-alpha-alkyl androgens
US6677329B1 (en)	2004-01-13	Non-aromatic estrogenic steroids with a hydrocarbon substituent in position 11
JP2010529153A (ja)	2010-08-26	１７β−シアノ−１９−ノル−アンドロスタ−４−エン誘導体、その使用、及び当該誘導体を含む医薬
US20060270845A1 (en)	2006-11-30	16-Hydroxyestratrienes as selectively active estrogens
HUT73238A (en)	1996-07-29	15,15-dialkyl-substituted derivatives of estradiol and pharmaceutical compositions containing the same
US20040059140A1 (en)	2004-03-25	14(15)-unsaturated 15- and/or 16-substituted androgens with mixed androgen-progrestational profile
JP2002539135A (ja)	2002-11-19	アンドロゲンとしての１４β，１７α−ヒドロキシメチルアンドロスタン誘導体
JP4279552B2 (ja)	2009-06-17	新規アンドロゲンとしてのメチレンステロイド