DK145140B - Analogifremgangsmaade til fremstilling af 6beta,7beta,15,16-dimethylen-1,4-androstadien-3-oner - Google Patents
Analogifremgangsmaade til fremstilling af 6beta,7beta,15,16-dimethylen-1,4-androstadien-3-oner Download PDFInfo
- Publication number
- DK145140B DK145140B DK234780AA DK234780A DK145140B DK 145140 B DK145140 B DK 145140B DK 234780A A DK234780A A DK 234780AA DK 234780 A DK234780 A DK 234780A DK 145140 B DK145140 B DK 145140B
- Authority
- DK
- Denmark
- Prior art keywords
- androstadien
- dimethylene
- hydroxy
- preparing
- ether
- Prior art date
Links
- 238000000034 method Methods 0.000 title description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 8
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- 238000010992 reflux Methods 0.000 claims description 5
- 239000000126 substance Substances 0.000 claims description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 3
- 239000000741 silica gel Substances 0.000 claims description 3
- 229910002027 silica gel Inorganic materials 0.000 claims description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 2
- 229910052700 potassium Inorganic materials 0.000 claims description 2
- 239000011591 potassium Substances 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims 3
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 claims 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims 2
- OHIVCUOZPIUUHH-DEPCRRQNSA-N (8s,9s,10r,13s,14s)-13-ethenyl-10-methyl-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-3-one Chemical compound C([C@@]1(CCC[C@H]1[C@@H]1CC2)C=C)C[C@@H]1[C@]1(C)C2=CC(=O)CC1 OHIVCUOZPIUUHH-DEPCRRQNSA-N 0.000 claims 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims 1
- 238000001816 cooling Methods 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims 1
- 239000002244 precipitate Substances 0.000 claims 1
- 150000003839 salts Chemical group 0.000 claims 1
- 238000003756 stirring Methods 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 8
- -1 15,16-methylene group Chemical group 0.000 abstract description 3
- 239000002934 diuretic Substances 0.000 abstract description 2
- 229940030606 diuretics Drugs 0.000 abstract description 2
- JPJALAQPGMAKDF-UHFFFAOYSA-N selenium dioxide Chemical compound O=[Se]=O JPJALAQPGMAKDF-UHFFFAOYSA-N 0.000 description 6
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 150000002596 lactones Chemical group 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000006356 dehydrogenation reaction Methods 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- ODZCIUXVJVQGKW-IFLJBQAJSA-N (8r,9s,10r,13r,14s)-10,13-dimethyl-15,16-dimethylidene-6,7,8,9,11,12,14,17-octahydrocyclopenta[a]phenanthren-3-one Chemical class C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C(=C)C(=C)C[C@@]1(C)CC2 ODZCIUXVJVQGKW-IFLJBQAJSA-N 0.000 description 1
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 1
- ZESRJSPZRDMNHY-YFWFAHHUSA-N 11-deoxycorticosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 ZESRJSPZRDMNHY-YFWFAHHUSA-N 0.000 description 1
- SJZRECIVHVDYJC-UHFFFAOYSA-N 4-hydroxybutyric acid Chemical compound OCCCC(O)=O SJZRECIVHVDYJC-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- PQSUYGKTWSAVDQ-ZVIOFETBSA-N Aldosterone Chemical compound C([C@@]1([C@@H](C(=O)CO)CC[C@H]1[C@@H]1CC2)C=O)[C@H](O)[C@@H]1[C@]1(C)C2=CC(=O)CC1 PQSUYGKTWSAVDQ-ZVIOFETBSA-N 0.000 description 1
- PQSUYGKTWSAVDQ-UHFFFAOYSA-N Aldosterone Natural products C1CC2C3CCC(C(=O)CO)C3(C=O)CC(O)C2C2(C)C1=CC(=O)CC2 PQSUYGKTWSAVDQ-UHFFFAOYSA-N 0.000 description 1
- 241000186063 Arthrobacter Species 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 241001402444 Diplomitoporus flavescens Species 0.000 description 1
- 241000589565 Flavobacterium Species 0.000 description 1
- 240000008609 Gloriosa superba Species 0.000 description 1
- 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 1
- 241000186660 Lactobacillus Species 0.000 description 1
- 240000001929 Lactobacillus brevis Species 0.000 description 1
- 241000193386 Lysinibacillus sphaericus Species 0.000 description 1
- 241000187654 Nocardia Species 0.000 description 1
- 241000589516 Pseudomonas Species 0.000 description 1
- LVAMVZXECCXUGI-UHFFFAOYSA-N acetic acid;thallium Chemical compound [Tl].CC(O)=O LVAMVZXECCXUGI-UHFFFAOYSA-N 0.000 description 1
- 229960002478 aldosterone Drugs 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- ZESRJSPZRDMNHY-UHFFFAOYSA-N de-oxy corticosterone Natural products O=C1CCC2(C)C3CCC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 ZESRJSPZRDMNHY-UHFFFAOYSA-N 0.000 description 1
- 229940119740 deoxycorticosterone Drugs 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229940039696 lactobacillus Drugs 0.000 description 1
- 229960001566 methyltestosterone Drugs 0.000 description 1
- 230000002906 microbiologic effect Effects 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 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
- 238000001556 precipitation Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- LXMSZDCAJNLERA-ZHYRCANASA-N spironolactone Chemical compound C([C@@H]1[C@]2(C)CC[C@@H]3[C@@]4(C)CCC(=O)C=C4C[C@H]([C@@H]13)SC(=O)C)C[C@@]21CCC(=O)O1 LXMSZDCAJNLERA-ZHYRCANASA-N 0.000 description 1
- 229960002256 spironolactone Drugs 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 230000007306 turnover Effects 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
- C07J53/008—3 membered carbocyclic rings in position 15/16
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/10—Antioedematous agents; Diuretics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Steroid Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Transition And Organic Metals Composition Catalysts For Addition Polymerization (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Control Of High-Frequency Heating Circuits (AREA)
- Ultra Sonic Daignosis Equipment (AREA)
- Oscillators With Electromechanical Resonators (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
U5U0
Opfindelsen angår en analogifremgangsmåde til fremstilling af hidtil ukendte 6S,7B,15,16-dimethylen-l,4-androstadien-3-oner med den almene formel i T l>ch2 hvori den 15,16-stillede methylengruppe kan være a- eller 5 β-stillet, og E betegner gruppen
I-Γ° Γ OH
X ' iCH2^ 30H eller CH2-CH2~COOK
De ifølge opfindelsen fremstillede forbindelser besidder værdifulde farmakologiske egenskaber. De er blandt andet diuretika af typen aldosteron-ar^tagonister, dvs., de kan vende virkningen af 10 desoxycorticosteron på natrium- og kaliumudskilleisen. Forbindelserne fremstillet ifølge opfindelsen viser sig i testmodellen i-følge Hollmann (G. Hollmann et al., Tubulåre Wirkungen und renale Elimination von Spirolactonen, Naunyn-Schmiedebergs Arch. Exp. Path. Pharmak. 247 (1964) 419; P. Marx, Renale 15 Wirkungen des d-Aldosterons und seines Antagonisten Spirono= lactons, Diss. Med. Fak. FU Berlin 1966) med hensyn til deres virkning at være overlegne i forhold til de kendte spirolactoner.
2 U5140
Den efterfølgende tabel godtgør nærmere den uventet nyttige biologiske virkning af de ifølge opfindelsen fremstillede forbindelser
TABEL
5 Forbindelse Relativ virkning °i i
0 J
0 CH3
Spironolacton, Sincomeri^
Dansk fremlæggelsesskrift nr. 142.951 OH
/-4'^Y<CH2l3OH
“ JZi
Dansk patentansøgning nr. 2138/78 0^=1 i 10-15 jdr
Eksempel 1 U5U0 3
Fremgangsmåden ifølge opfindelsen til fremstilling af de tidligere nævnte hidtil ukendte forbindelser er ejendommelig ved, at man på i og for sig kendt måde indfører Δ^-dobbelt-bindingen i tilsvarende 6β, 7(3,15,16-dimethylen-4-androsten-5 3-oner og derpå i givet fald spalter lactonringen.
Indføringen af Δ^-dobbeltbindingen sker ifølge i og for sig kendte metoder og kan ske ad kemisk eller mikrobiologisk vej. Egnede kemiske dehydrogeneringsmidler til l,2-dehydro= generingen er f.eks. selendioxid, 2,3-dichlor-5,6-dicyan= 10 benzoquinon, chloranil, thalliumtriacetat eller blytetra= acetat. Egnede mikroorganismer til 1,2-dehydrogeneringen er f.eks. Schizomyceter, specielt sådanne af slægterne Arthro= bacter, som f.eks. simplex ATCC 6946, Bacillus, som f.eks.
B. Léntus ATCC 13805 og B. sphaericus ATCC 7055, Pseudomonas, 15 som f.eks. P. aeruginosa IFO 3505, Flavobacterium, som f.eks.
F. flavescens IFO 3058, Lactobacillus, som f.eks. L. brevis IFO 3345 og Nocardia, som f.eks. N, opaca ATCC 4276.
1,2-dehydroqeneringen udføres fortrinsvis ad kemisk vej. Hertil opvarmes 1,2-dihydrosteroidet i et egnet opløsningsmid-20 del med dehydrogeneringsmidler i et længere tidsrum. Egnede opløsningsmidler er f.eks. dioxan, tert.-butanol, tetrahydro= furan, toluen, benzen henholdsvis blandinger af disse opløsningsmidler.
Reaktionen er afsluttet efter flere timers forløb. Det kan 25 tilrådes at følge omsætningen ved hjælp af tyndtlagskroma- tografi. Reaktionsblandingen oparbejdes, når udgangsmaterialet er omsat.
Den eventuelt efterfølgende åbning af lactonringen sker ligeledes ved hjælp af i og for sig kendte metoder. Hertil op-30 varmes lactonen med fortyndet kaliumhydroxid, hvorved dannes kaliumsaltet af den 3-substituerede propionsyre.
Efter endt reaktion oparbejdes reaktionsblandingen på sædvanlig måde, såsom fældning, ekstraktion, omkrystallisation og/ eller kromatografi.
U5U0 4 JDe ifølge opfindelsen fremstillede forbindelser anvendes ifølge 1 og for sig kendte galeniske metoder til fremstillingen af lægemidler til oral eller parenteral applikation.
Doseringen af forbindelserne ligger hos mennesker på 5 10-200 mg/dag.
De efterfølgende eksempler tjener til nærmere belysning af opfindelsen.
Eksempel 1.
500 mg 63,70,150,160-dimethylen-4-androsten-[17(0-1')-spiro-10 5'iperhydrofuran-2',3-dion opvarmes i 7,5 ml dioxan med 1 500 mg 2,3-dichlor-5,6-dicyan-p-benzoquinon i 17 timer un der tilbagesvaling. Derpå fortyndes med ether, vaskes med mættet natriumhydrogencarbonatopløsning og vand, tørres og inddampes. Resten kromatograferes på silicagel. Der fås 330 15 mg 60,70,150,160-dimethylen-l,4-androstadien-[17(0-l,)- spiro-51]-perhydrofuran-2',3-dion med smeltepunkt 250,5 -252°C. ’ ·.
UV: ε245 =12.000, ε286 = 9.950.
Eksempel 2.
20 300 mg 60,70,15a,16a-dimethylen-4-androsten-[17(0-1')-Spiro s' ]perhydrofuran-2',3-dion omrøres i 15 ml tert.-butanol - med 90 mg selendioxid og 0,5 ml eddikesyre i 20 timer under tilbagesvaling. Derpå tilsættes yderligere 90 mg selendioxid og opvarmes i endnu 24 timer under tilbagesvaling. Efter 25 inddampning til tørhed kromatograferes resten på silicagel.
Der fås 120 mg 60,70,15a,16a-dimethylen-1,4-androstadien-117(0-1')-spiro-51]perhydrofuran-2',3-dion.
UV; ε245 = 11.800, ε285 = 9.800.
Eksempel 3.
30 500 mg 60,70,150,160-dimethylen-l,4-androstadien-[17(Ø-l1) -
Claims (2)
145140 spiro-5'lperhydrofuran-2',3-dion behandles i 5 ml isopropa= nol med 1,37 ml IN kaliumhydroxid i methanol og opvarmes i 1 time under tilbagesvaling. Efter afkøling tilsættes 30 ml absolut ether og efterrøres i 1 time på isbad. Det udkrystal-5 liserede bundfald frasuges derpå, vaskes omhyggeligt med ether og tørres. Der fås 510 mg 3(17|3-hydroxy-6|3,73,15|3,160-dimethylen-3-oxo-l,4-androstadien-17a-yl)-propionsyre-kali= umsalt. UV; ε245 = 11*500, ε286 ~ 9*600.
10 Eksempel 4. 300 mg 17g-hydroxy-17a-(3-hydroxypropyl)-6β,73,15β,16β-άϊ= methylen-4-androsten-3-on opvarmes i 9 ml dioxan med 300 mg 2,3-dichlor-5,6-dicyan-p-benzoquinon i 17 timer under tilbagesvaling. Derpå fortyndes med ether, vaskes med mættet 15 natriumhydrogencarbonatopløsning og vand, tørres og inddam pes. Resten kromatograferes på silicagel. Som et amorft stof fås 120 mg 17f3-hydroxy-17a-(3-hydroxypropyl)-6β,7β,15β, 160-dime thy len-1 ,4-androstadien-3-on. UV; ε244 = 11.500, e285 = 9.600. Patentkrav, 20 1 . Analcgifremgangsmåde til fremstilling af 6P,70,15,16-diirethy= len-1,4-androstadien-3-oner med den almene formel hvori den 15,16-stillede methylengruppe kan være a- eller β-stillet, og E betegner gruppen
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19792922500 DE2922500A1 (de) | 1979-05-31 | 1979-05-31 | 6 beta .7 beta |
| DE2922500 | 1979-05-31 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DK234780A DK234780A (da) | 1980-12-01 |
| DK145140B true DK145140B (da) | 1982-09-13 |
| DK145140C DK145140C (da) | 1983-02-21 |
Family
ID=6072347
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK234780A DK145140C (da) | 1979-05-31 | 1980-05-30 | Analogifremgangsmaade til fremstilling af 6beta,7beta,15,16-dimethylen-1,4-androstadien-3-oner |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US4291029A (da) |
| EP (1) | EP0019690B1 (da) |
| JP (1) | JPS55162799A (da) |
| AT (1) | ATE880T1 (da) |
| AU (1) | AU531057B2 (da) |
| CA (1) | CA1134814A (da) |
| CS (1) | CS214712B2 (da) |
| DD (1) | DD151172A5 (da) |
| DE (2) | DE2922500A1 (da) |
| DK (1) | DK145140C (da) |
| ES (1) | ES8101082A1 (da) |
| HU (2) | HU187419B (da) |
| IE (1) | IE49899B1 (da) |
| IL (1) | IL60185A (da) |
| SU (1) | SU873890A3 (da) |
| YU (1) | YU41926B (da) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3111951A1 (de) * | 1981-03-23 | 1982-09-30 | Schering Ag, 1000 Berlin Und 4619 Bergkamen | 7(alpha)-alkoxycarbonyl-15ss-methylen-4-androstene, verfahren zu ihrer herstellung und verwendung als arzneimittel |
| DE3213962A1 (de) * | 1982-04-13 | 1983-10-13 | Schering AG, 1000 Berlin und 4709 Bergkamen | 1(alpha).2(alpha);6(beta).7(beta).15(beta).16(beta)-trimethylen-3-oxo-17(alpha)-pregn-4-en-21.17-carbolacton, dessen herstellung und verwendung als arzneimittel |
| DE3222265A1 (de) * | 1982-06-09 | 1983-12-15 | Schering AG, 1000 Berlin und 4709 Bergkamen | 6ss.7ss-methylen-17(alpha)-pregn-4-en-21.17-carbolactone, verfahren zu ihrer herstellung und verwendung als arzneimittel |
| DE3227598A1 (de) * | 1982-07-22 | 1984-01-26 | Schering AG, 1000 Berlin und 4709 Bergkamen | 7(alpha)-acylthio-15.16-methylen-3-oxo-17(alpha)-pregna-1.4-dien-21,17-carbolactone, verfahren zu ihrer herstellung und verwendung als arzneimittel |
| JPS5921698A (ja) * | 1982-07-22 | 1984-02-03 | シエ−リング・アクチエンゲゼルシヤフト | １７α−プレグネ−４−エン−３−オキソ−２１−カルボン酸エステル、その製法およびこれを含有する抗アンドロゲン作用を有する医薬 |
| DE3240510A1 (de) * | 1982-10-29 | 1984-05-03 | Schering AG, 1000 Berlin und 4709 Bergkamen | Neue 7(alpha)-acylthio-1(alpha),2(alpha)-methylen-3-oxo-17(alpha)-pregn-4-en-21,17-carbolactone, deren herstellung und diese enthaltende arzneimittel |
| FI77669C (fi) * | 1983-04-13 | 1989-04-10 | Ciba Geigy Ag | 20-spiroxaner och analoger, som innehaoller en oeppen ring e, foerfarande foer deras framstaellning samt dessa innehaollande farmaceutiska preparat. |
| DE3326013A1 (de) * | 1983-07-15 | 1985-01-24 | Schering AG, 1000 Berlin und 4709 Bergkamen | 15,16-methylen-17(alpha)-pregna-4,6-dien-21-carbonsaeuresalze, diese enthaltende pharmazeutische praeparate sowie verfahren zu deren herstellung |
| EP0134529B1 (de) * | 1983-08-17 | 1990-03-21 | Schering Aktiengesellschaft | 7-alpha-Substituierte 3-Oxo-17alpha-pregn-4-en-21.17-carbolactone, Verfahren zu ihrer Herstellung und diese enthaltende pharmazeutische Präparate |
| DE3410880A1 (de) * | 1984-03-21 | 1985-10-03 | Schering AG, Berlin und Bergkamen, 1000 Berlin | 17-substituierte estradiene und estratriene |
| FR2697328A1 (fr) * | 1992-10-23 | 1994-04-29 | Giat Ind Sa | Munition fumigène. |
| US6787531B1 (en) * | 1999-08-31 | 2004-09-07 | Schering Ag | Pharmaceutical composition for use as a contraceptive |
| US20020132801A1 (en) * | 2001-01-11 | 2002-09-19 | Schering Aktiengesellschaft | Drospirenone for hormone replacement therapy |
| DE102007027637A1 (de) | 2007-06-12 | 2008-12-18 | Bayer Schering Pharma Aktiengesellschaft | 17ß-Cyano-19-nor-androst-4-en-Derivat, dessen Verwendung und das Derivat enthaltende Arzneimittel |
| DE102007027635A1 (de) | 2007-06-12 | 2008-12-18 | Bayer Schering Pharma Aktiengesellschaft | 17ß-Cyano-19-androst-4-en-Derivat, dessen Verwendung und das Derivat enthaltende Arzneimittel |
| DE102007027636A1 (de) | 2007-06-12 | 2008-12-18 | Bayer Schering Pharma Aktiengesellschaft | 17ß-Cyano-18a-homo-19-nor-androst-4-en-Derivat, dessen Verwendung und das Derivat enthaltende Arzneimittel |
| DE102007063498A1 (de) | 2007-12-29 | 2009-07-02 | Bayer Schering Pharma Aktiengesellschaft | 15,16-Methylen-steroid-17,17-Lactol-Derivat, dessen Verwendung und das Derivat enthaltende Arzneimittel |
| DE102007063500A1 (de) | 2007-12-29 | 2009-07-02 | Bayer Schering Pharma Aktiengesellschaft | 17-(1'-Propenyl)-17-3'-oxidoestra-4-en-3-on-Derivat, dessen Verwendung und das Derivat enthaltende Arzneimittel |
| DE102007063496A1 (de) | 2007-12-29 | 2009-07-02 | Bayer Schering Pharma Aktiengesellschaft | 15,16-Methylen-17-(1'-propenyl)-17-3'-oxidoestra-4-en-3-on-Derivat, dessen Verwendung und das Derivat enthaltende Arzneimittel |
| DE102007063499A1 (de) | 2007-12-29 | 2009-07-02 | Bayer Schering Pharma Aktiengesellschaft | Steroid-17,17-Lactol-Derivat, dessen Verwendung und das Derivat enthaltende Arzneimittel |
| DE102007063501A1 (de) | 2007-12-29 | 2009-07-02 | Bayer Schering Pharma Aktiengesellschaft | 15, 16-Methylen-17-hydroxy-19-nor-21-carbonsäure-Steroid y-Lacton-Derivat, dessen Verwendung und das Derivat enthaltende Arzneimittel |
| DE102007063495A1 (de) | 2007-12-29 | 2009-09-17 | Bayer Schering Pharma Aktiengesellschaft | 19-Nor-Steroidderivate mit einer 15α,16α-Methylengruppe und einem gesättigten 17,17-Spirolactonring, deren Verwendung sowie diese Derivate enthaltende Arzneimittel |
| DE102007063503A1 (de) | 2007-12-29 | 2009-07-02 | Bayer Schering Pharma Aktiengesellschaft | 17-Hydroxy-19-nor-21-carbonsäure-Steroid y-Lacton-Derivat, dessen Verwendung und das Derivat enthaltende Arzneimittel |
| DE102008026793A1 (de) | 2008-06-02 | 2009-12-03 | Bayer Schering Pharma Aktiengesellschaft | C-Ring-substituierte Pregn-4-en-21,17-carbolactone, sowie diese enthaltende pharmazeutische Präparate |
| CA2854215A1 (en) | 2011-11-04 | 2013-05-10 | Bayer Pharma Aktiengesellschaft | 18-methyl-6,7-methylene-3-oxo-17-pregn-4-ene-21,17.beta.-carbolactones, pharmaceutical preparations comprising said compounds and use thereof in the treatment of endometriosis |
| WO2016063269A1 (en) | 2014-10-20 | 2016-04-28 | Prendergast Patrick T | Use of antagonists to the nuclear steroid receptor alone or in combination as direct antiviral agents to inhibit alphavirus, togaviridae, arenaviridae, filoviridae, bunyaviridae, flaviviridae and rhabdoviridae |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3254074A (en) * | 1962-04-25 | 1966-05-31 | Merck & Co Inc | Spiroxenones |
| DE2264189C3 (de) * | 1972-12-29 | 1979-05-31 | Merck & Co., Inc., Rahway, N.J. (V.St.A.) | 3'-(3-Oxo-17beta-hydroxy-6,7-methylen-androst-4en-bzw.-l,4-dien-17 a-yl) -propionsäureverbindungen, Verfahren zu ihrer Herstellung sowie diese enthaltende pharmazeutische Mittel |
| DE2652761C2 (de) * | 1976-11-16 | 1985-11-21 | Schering AG, 1000 Berlin und 4709 Bergkamen | 15,16-Methylen-Spirolactone, Verfahren zu deren Herstellung und diese enthaltende Arzneimittel |
| ES469510A1 (es) * | 1977-05-16 | 1978-12-01 | Schering Ag | Procedimiento para la preparacion de 17beta hidroxi-4-an- drosten-3-onas. |
-
1979
- 1979-05-31 DE DE19792922500 patent/DE2922500A1/de not_active Withdrawn
-
1980
- 1980-03-17 DE DE8080101383T patent/DE3060297D1/de not_active Expired
- 1980-03-17 AT AT80101383T patent/ATE880T1/de active
- 1980-03-17 EP EP80101383A patent/EP0019690B1/de not_active Expired
- 1980-04-11 SU SU802907605A patent/SU873890A3/ru active
- 1980-05-19 YU YU1329/80A patent/YU41926B/xx unknown
- 1980-05-26 AU AU58745/80A patent/AU531057B2/en not_active Ceased
- 1980-05-26 JP JP6907980A patent/JPS55162799A/ja active Granted
- 1980-05-27 CS CS803714A patent/CS214712B2/cs unknown
- 1980-05-28 ES ES491916A patent/ES8101082A1/es not_active Expired
- 1980-05-29 DD DD80221451A patent/DD151172A5/de not_active IP Right Cessation
- 1980-05-29 US US06/154,194 patent/US4291029A/en not_active Expired - Lifetime
- 1980-05-29 IL IL60185A patent/IL60185A/xx unknown
- 1980-05-30 HU HU803323A patent/HU187419B/hu not_active IP Right Cessation
- 1980-05-30 DK DK234780A patent/DK145140C/da not_active IP Right Cessation
- 1980-05-30 HU HU801372A patent/HU181714B/hu not_active IP Right Cessation
- 1980-05-30 IE IE1127/80A patent/IE49899B1/en not_active IP Right Cessation
- 1980-05-30 CA CA000353151A patent/CA1134814A/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| SU873890A3 (ru) | 1981-10-15 |
| CS214712B2 (en) | 1982-05-28 |
| DK145140C (da) | 1983-02-21 |
| HU181714B (en) | 1983-11-28 |
| DD151172A5 (de) | 1981-10-08 |
| DE2922500A1 (de) | 1980-12-04 |
| DE3060297D1 (en) | 1982-06-03 |
| ES491916A0 (es) | 1980-12-16 |
| AU5874580A (en) | 1980-12-04 |
| HU187419B (en) | 1986-01-28 |
| JPH0214360B2 (da) | 1990-04-06 |
| ATE880T1 (de) | 1982-05-15 |
| IL60185A (en) | 1983-06-15 |
| YU41926B (en) | 1988-02-29 |
| CA1134814A (en) | 1982-11-02 |
| IL60185A0 (en) | 1980-07-31 |
| JPS55162799A (en) | 1980-12-18 |
| AU531057B2 (en) | 1983-08-11 |
| ES8101082A1 (es) | 1980-12-16 |
| DK234780A (da) | 1980-12-01 |
| IE801127L (en) | 1980-11-30 |
| EP0019690B1 (de) | 1982-04-21 |
| YU132980A (en) | 1983-02-28 |
| IE49899B1 (en) | 1986-01-08 |
| EP0019690A1 (de) | 1980-12-10 |
| US4291029A (en) | 1981-09-22 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PBP | Patent lapsed |