CZ301376B6 - Steroidní deriváty s androgenním úcinkem - Google Patents
Steroidní deriváty s androgenním úcinkem Download PDFInfo
- Publication number
- CZ301376B6 CZ301376B6 CZ20021894A CZ20021894A CZ301376B6 CZ 301376 B6 CZ301376 B6 CZ 301376B6 CZ 20021894 A CZ20021894 A CZ 20021894A CZ 20021894 A CZ20021894 A CZ 20021894A CZ 301376 B6 CZ301376 B6 CZ 301376B6
- Authority
- CZ
- Czechia
- Prior art keywords
- methyl
- alkyl
- methoxy
- product
- hydrogen
- Prior art date
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- 230000001548 androgenic effect Effects 0.000 title claims abstract description 16
- 230000003637 steroidlike Effects 0.000 title description 3
- 230000001747 exhibiting effect Effects 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 67
- 239000003098 androgen Substances 0.000 claims abstract description 19
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 32
- 239000001257 hydrogen Substances 0.000 claims description 26
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 25
- 125000000217 alkyl group Chemical group 0.000 claims description 19
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 16
- 229910052736 halogen Inorganic materials 0.000 claims description 11
- 150000002367 halogens Chemical group 0.000 claims description 11
- 150000002431 hydrogen Chemical class 0.000 claims description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 125000002252 acyl group Chemical group 0.000 claims description 5
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 3
- 125000000304 alkynyl group Chemical group 0.000 claims description 3
- 150000001993 dienes Chemical class 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- JFEPJTGMGDGPHJ-PNKHAZJDSA-N (8r,9s,10r,13s,14s)-13-methyl-2,6,7,8,9,10,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-3-one Chemical compound C1CC2=CC(=O)CC[C@@H]2[C@@H]2[C@@H]1[C@@H]1CCC[C@@]1(C)CC2 JFEPJTGMGDGPHJ-PNKHAZJDSA-N 0.000 claims description 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 2
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 239000003381 stabilizer Substances 0.000 claims description 2
- 150000001345 alkine derivatives Chemical class 0.000 claims 1
- 230000003054 hormonal effect Effects 0.000 claims 1
- 239000002583 male contraceptive agent Substances 0.000 claims 1
- 150000003431 steroids Chemical class 0.000 abstract description 24
- 238000002360 preparation method Methods 0.000 abstract description 4
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 abstract 1
- 239000003795 chemical substances by application Substances 0.000 abstract 1
- 239000000047 product Substances 0.000 description 109
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 96
- 239000000243 solution Substances 0.000 description 72
- 238000000034 method Methods 0.000 description 58
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 47
- 239000000203 mixture Substances 0.000 description 42
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 35
- 239000012267 brine Substances 0.000 description 35
- 239000012074 organic phase Substances 0.000 description 35
- 229910052938 sodium sulfate Inorganic materials 0.000 description 35
- 235000011152 sodium sulphate Nutrition 0.000 description 35
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 35
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
- 239000011541 reaction mixture Substances 0.000 description 31
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 25
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 24
- 238000003756 stirring Methods 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 23
- 238000004440 column chromatography 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
- -1 steroid compounds Chemical class 0.000 description 19
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- 238000000746 purification Methods 0.000 description 17
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 17
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 125000004432 carbon atom Chemical group C* 0.000 description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 13
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 11
- 235000019270 ammonium chloride Nutrition 0.000 description 11
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 10
- 235000017557 sodium bicarbonate Nutrition 0.000 description 10
- 229960001124 trientine Drugs 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- 238000006722 reduction reaction Methods 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 229940030486 androgens Drugs 0.000 description 8
- 230000009467 reduction Effects 0.000 description 8
- 150000003839 salts Chemical class 0.000 description 8
- 238000006027 Birch reduction reaction Methods 0.000 description 7
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 7
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 7
- 239000000583 progesterone congener Substances 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- 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 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 125000003545 alkoxy group Chemical group 0.000 description 6
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 6
- 230000007062 hydrolysis Effects 0.000 description 6
- 238000006460 hydrolysis reaction Methods 0.000 description 6
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
- RGICCULPCWNRAB-UHFFFAOYSA-N 2-[2-(2-hexoxyethoxy)ethoxy]ethanol Chemical compound CCCCCCOCCOCCOCCO RGICCULPCWNRAB-UHFFFAOYSA-N 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 239000000460 chlorine Substances 0.000 description 5
- 230000002254 contraceptive effect Effects 0.000 description 5
- 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 5
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- 125000001424 substituent group Chemical group 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 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
- 125000004043 oxo group Chemical group O=* 0.000 description 4
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 4
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 206010002261 Androgen deficiency Diseases 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
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-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
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 125000004122 cyclic group Chemical group 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
- 238000002657 hormone replacement therapy Methods 0.000 description 3
- 238000005984 hydrogenation reaction Methods 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 229960004719 nandrolone Drugs 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 229960003604 testosterone Drugs 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
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- NVKAWKQGWWIWPM-ABEVXSGRSA-N 17-β-hydroxy-5-α-Androstan-3-one Chemical compound C1C(=O)CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CC[C@H]21 NVKAWKQGWWIWPM-ABEVXSGRSA-N 0.000 description 2
- VILCJCGEZXAXTO-UHFFFAOYSA-N 2,2,2-tetramine Chemical compound NCCNCCNCCN VILCJCGEZXAXTO-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
- RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 2
- LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical compound C1CC1 LVZWSLJZHVFIQJ-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
- 239000002841 Lewis acid Substances 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 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
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 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
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 239000007864 aqueous solution Substances 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
- 229910052799 carbon Inorganic materials 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 229940126214 compound 3 Drugs 0.000 description 2
- 239000003433 contraceptive agent Substances 0.000 description 2
- 229940116318 copper carbonate Drugs 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
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 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
- 150000007517 lewis acids Chemical class 0.000 description 2
- 125000002524 organometallic group Chemical group 0.000 description 2
- 239000000546 pharmaceutical excipient 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
- 239000002243 precursor Substances 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 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
- 239000007787 solid Substances 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 239000013589 supplement Substances 0.000 description 2
- 230000009469 supplementation Effects 0.000 description 2
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 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
- KBIJNEVVKLELIK-MPSBBLFHSA-N (7r,8r,9s,13s,14s)-7-ethyl-3-hydroxy-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(O)=CC=C3[C@H]21 KBIJNEVVKLELIK-MPSBBLFHSA-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
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Classifications
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- 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)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP99204080 | 1999-12-02 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CZ20021894A3 CZ20021894A3 (cs) | 2002-08-14 |
| CZ301376B6 true CZ301376B6 (cs) | 2010-02-03 |
Family
ID=8240955
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CZ20021894A CZ301376B6 (cs) | 1999-12-02 | 2000-11-29 | Steroidní deriváty s androgenním úcinkem |
Country Status (27)
| Country | Link |
|---|---|
| US (1) | US6706700B2 (enExample) |
| EP (1) | EP1237904B1 (enExample) |
| JP (1) | JP2003515543A (enExample) |
| CN (1) | CN1166680C (enExample) |
| AR (1) | AR026655A1 (enExample) |
| AT (1) | ATE317396T1 (enExample) |
| AU (1) | AU778017B2 (enExample) |
| CA (1) | CA2390226A1 (enExample) |
| CO (1) | CO5251441A1 (enExample) |
| CY (1) | CY1106086T1 (enExample) |
| CZ (1) | CZ301376B6 (enExample) |
| DE (1) | DE60025958T2 (enExample) |
| DK (1) | DK1237904T3 (enExample) |
| ES (1) | ES2258037T3 (enExample) |
| HK (1) | HK1047596B (enExample) |
| HU (1) | HUP0203611A3 (enExample) |
| IL (1) | IL149424A (enExample) |
| MX (1) | MXPA02004939A (enExample) |
| NO (1) | NO322422B1 (enExample) |
| NZ (1) | NZ518753A (enExample) |
| PE (1) | PE20011033A1 (enExample) |
| PL (1) | PL202999B1 (enExample) |
| RU (1) | RU2242479C2 (enExample) |
| SK (1) | SK287095B6 (enExample) |
| TW (1) | TWI275593B (enExample) |
| WO (1) | WO2001040255A2 (enExample) |
| ZA (1) | ZA200203536B (enExample) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU5209600A (en) * | 1999-04-06 | 2000-10-23 | Akzo Nobel N.V. | Orally active androgens |
| RS51490B (sr) * | 2002-01-21 | 2011-04-30 | N.V. Organon | POSTUPAK ZA IZRADU 7α-METILSTEROIDA |
| US20080293683A1 (en) * | 2007-05-24 | 2008-11-27 | University Of Kansas Medical Center | Hormone Replacement Therapy |
| EP2383279A1 (en) | 2011-07-19 | 2011-11-02 | Pantarhei Bioscience B.V. | Process for the preparation of estetrol |
| PL2764008T3 (pl) * | 2011-10-07 | 2017-04-28 | Estetra S.P.R.L. | Sposób wytwarzania estetrolu |
| JP6863547B2 (ja) | 2015-06-18 | 2021-04-21 | 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 | エステトロール成分を含有する口腔内崩壊性投与単位 |
| JP6866560B2 (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 | エステトロール成分を含有する口腔内崩壊性投与単位 |
| MA44206B1 (fr) | 2015-06-18 | 2021-04-30 | Estetra Sprl | Comprimé orodispersible comprenant estetrol |
| LT3310345T (lt) | 2015-06-18 | 2021-06-25 | Estetra Sprl | Burnoje disperguojama tabletė, turinti estetrolio |
| CA3178291A1 (en) | 2016-08-05 | 2018-04-12 | Estetra Srl | Method for the management of dysmenorrhea and menstrual pain |
| 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 |
| JOP20200260A1 (ar) | 2018-04-19 | 2019-10-19 | Estetra Sprl | مركبات واستخداماتها للتخفيف من الأعراض المصاحبة لانقطاع الطمث |
| 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 |
| 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 |
Citations (3)
| 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 |
| EP0277676A1 (en) * | 1987-01-23 | 1988-08-10 | Akzo N.V. | New ll-aryl steroid derivatives |
| EP0768316A1 (de) * | 1995-10-10 | 1997-04-16 | JENAPHARM GmbH | Steroide mit einer 14,15, Methylengruppe |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 (en) * | 1999-03-08 | 2000-09-14 | Akzo Nobel N.V. | 14.beta., 17-alpha-hydroxymethylandrostane derivatives as androgens |
-
2000
- 2000-11-29 PL PL355689A patent/PL202999B1/pl not_active IP Right Cessation
- 2000-11-29 JP JP2001541010A patent/JP2003515543A/ja active Pending
- 2000-11-29 AU AU28383/01A patent/AU778017B2/en not_active Ceased
- 2000-11-29 HU HU0203611A patent/HUP0203611A3/hu unknown
- 2000-11-29 RU RU2002117440/04A patent/RU2242479C2/ru not_active IP Right Cessation
- 2000-11-29 HK HK02109169.4A patent/HK1047596B/en not_active IP Right Cessation
- 2000-11-29 NZ NZ518753A patent/NZ518753A/en unknown
- 2000-11-29 AT AT00993259T patent/ATE317396T1/de not_active IP Right Cessation
- 2000-11-29 CZ CZ20021894A patent/CZ301376B6/cs not_active IP Right Cessation
- 2000-11-29 MX MXPA02004939A patent/MXPA02004939A/es active IP Right Grant
- 2000-11-29 DE DE60025958T patent/DE60025958T2/de not_active Expired - Lifetime
- 2000-11-29 IL IL149424A patent/IL149424A/en not_active IP Right Cessation
- 2000-11-29 EP EP00993259A patent/EP1237904B1/en not_active Expired - Lifetime
- 2000-11-29 US US10/148,820 patent/US6706700B2/en not_active Expired - Fee Related
- 2000-11-29 ES ES00993259T patent/ES2258037T3/es not_active Expired - Lifetime
- 2000-11-29 DK DK00993259T patent/DK1237904T3/da active
- 2000-11-29 SK SK758-2002A patent/SK287095B6/sk not_active IP Right Cessation
- 2000-11-29 CA CA002390226A patent/CA2390226A1/en not_active Abandoned
- 2000-11-29 WO PCT/EP2000/012009 patent/WO2001040255A2/en not_active Ceased
- 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 CO CO00092012A patent/CO5251441A1/es not_active Application Discontinuation
- 2000-12-01 PE PE2000001285A patent/PE20011033A1/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
-
2006
- 2006-04-10 CY CY20061100500T patent/CY1106086T1/el unknown
Patent Citations (3)
| 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 |
| EP0277676A1 (en) * | 1987-01-23 | 1988-08-10 | Akzo N.V. | New ll-aryl steroid derivatives |
| EP0768316A1 (de) * | 1995-10-10 | 1997-04-16 | JENAPHARM GmbH | Steroide mit einer 14,15, Methylengruppe |
Also Published As
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| KR100730010B1 (ko) | 신규 안드로겐 | |
| EP1343806B1 (en) | Methylene steroids as novel androgens | |
| WO2002048169A1 (en) | 14(15)-unsaturated 15- and/or 16- substituted androgens with mixed androgen-progestational profile | |
| AU2002224923A1 (en) | Methylene steroids as novel androgens |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Patent lapsed due to non-payment of fee |
Effective date: 20101129 |