DK164873B - 3-keto-17alfa-mercapto-17beta-(substitueret thio)-androstenderivater med anvendelse som mellemprodukter ved fremstillingen af 17,17-bis(substitueret thio)-3-ketoandrostener samt fremgangsmaade til deres fremstilling - Google Patents
3-keto-17alfa-mercapto-17beta-(substitueret thio)-androstenderivater med anvendelse som mellemprodukter ved fremstillingen af 17,17-bis(substitueret thio)-3-ketoandrostener samt fremgangsmaade til deres fremstilling Download PDFInfo
- Publication number
- DK164873B DK164873B DK407983A DK407983A DK164873B DK 164873 B DK164873 B DK 164873B DK 407983 A DK407983 A DK 407983A DK 407983 A DK407983 A DK 407983A DK 164873 B DK164873 B DK 164873B
- Authority
- DK
- Denmark
- Prior art keywords
- substituted thio
- formula
- preparation
- hydrogen
- intermediates
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 8
- 239000000543 intermediate Substances 0.000 title abstract description 5
- SCVJRXQHFJXZFZ-KVQBGUIXSA-N 2-amino-9-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-3h-purine-6-thione Chemical class C1=2NC(N)=NC(=S)C=2N=CN1[C@H]1C[C@H](O)[C@@H](CO)O1 SCVJRXQHFJXZFZ-KVQBGUIXSA-N 0.000 title 2
- 150000001443 androstenes Chemical class 0.000 claims abstract description 5
- 150000001875 compounds Chemical class 0.000 claims description 5
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 claims description 4
- 239000002841 Lewis acid Substances 0.000 claims description 4
- 229910000037 hydrogen sulfide Inorganic materials 0.000 claims description 4
- 150000007517 lewis acids Chemical class 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 3
- 150000003431 steroids Chemical class 0.000 abstract description 9
- 239000001257 hydrogen Substances 0.000 abstract description 8
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 8
- 229910052736 halogen Chemical group 0.000 abstract description 6
- 150000002367 halogens Chemical group 0.000 abstract description 6
- 125000000217 alkyl group Chemical group 0.000 abstract description 4
- -1 aroyloxyalkyl Chemical group 0.000 abstract description 4
- 150000002431 hydrogen Chemical group 0.000 abstract description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract description 3
- 125000004423 acyloxy group Chemical group 0.000 abstract description 2
- 125000003545 alkoxy group Chemical group 0.000 abstract description 2
- 230000003110 anti-inflammatory effect Effects 0.000 abstract description 2
- 125000001589 carboacyl group Chemical group 0.000 abstract 3
- 125000003710 aryl alkyl group Chemical group 0.000 abstract 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 abstract 2
- 125000005041 acyloxyalkyl group Chemical group 0.000 abstract 1
- 125000004183 alkoxy alkyl group Chemical group 0.000 abstract 1
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 abstract 1
- 125000006350 alkyl thio alkyl group Chemical group 0.000 abstract 1
- 125000003435 aroyl group Chemical group 0.000 abstract 1
- 125000003118 aryl group Chemical group 0.000 abstract 1
- 125000005110 aryl thio group Chemical group 0.000 abstract 1
- 125000004104 aryloxy group Chemical group 0.000 abstract 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 abstract 1
- 125000004181 carboxyalkyl group Chemical group 0.000 abstract 1
- 125000000753 cycloalkyl group Chemical group 0.000 abstract 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 abstract 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 abstract 1
- 125000004043 oxo group Chemical group O=* 0.000 abstract 1
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-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
- 238000006243 chemical reaction Methods 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- NXQOQNROJJFYCJ-FZFXZXLVSA-N androst-16-ene Chemical compound C1CCC[C@]2(C)[C@H]3CC[C@](C)(C=CC4)[C@@H]4[C@@H]3CCC21 NXQOQNROJJFYCJ-FZFXZXLVSA-N 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- KVNYFPKFSJIPBJ-UHFFFAOYSA-N 1,2-diethylbenzene Chemical compound CCC1=CC=CC=C1CC KVNYFPKFSJIPBJ-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 201000004624 Dermatitis Diseases 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- VWPFYISYYYKCOY-DEPCRRQNSA-N (8r,9s,10r,13r,14s)-10-methyl-13-(methylsulfanylmethyl)-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-3-one Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CCC[C@@]1(CSC)CC2 VWPFYISYYYKCOY-DEPCRRQNSA-N 0.000 description 1
- PRIFTENTNWLAAB-RYMRXWPBSA-N (8s,9r,10s,11s,13s,14s)-17-ethylsulfanyl-9-fluoro-11-hydroxy-10,13-dimethyl-7,8,11,12,14,15-hexahydro-6h-cyclopenta[a]phenanthren-3-one Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1CC=C(SCC)[C@@]1(C)C[C@@H]2O PRIFTENTNWLAAB-RYMRXWPBSA-N 0.000 description 1
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 1
- OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-dichlorobenzene Chemical compound ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-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
- 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
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 1
- 201000009053 Neurodermatitis Diseases 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 206010042496 Sunburn Diseases 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 125000002777 acetyl group Chemical class [H]C([H])([H])C(*)=O 0.000 description 1
- 150000001351 alkyl iodides Chemical class 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 239000000538 analytical sample Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 208000010668 atopic eczema Diseases 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
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 229940117389 dichlorobenzene Drugs 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 150000004965 peroxy acids Chemical class 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J31/00—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring
- C07J31/003—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring the S atom directly linked to a ring carbon atom of the cyclopenta(a)hydrophenanthrene skeleton
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Steroid Compounds (AREA)
- Cosmetics (AREA)
Description
i
DK 164873 B
Den foreliggende opfindelse angår hidtil ukendte 3-keto-17a-mercapto-17/8- (substitueret thio) -androstenderivater, som er ejendommelige ved, at de har den almene formel 5 ?2 5 S ^ k hvor den stiplede linie i ringen betegner en fakultativ binding, R2 er C^^-alkyl, C3_5-cycloalkyl eller phenyl, R3 15 er hydrogen, hydroxy, C1_4-alkoxy eller alkanoyloxy med 1-4 alkylcarbonatomer, R4 er β-hydroxymethylen, R5 er hydrogen eller halogen, og Rg er hydrogen eller halogen.
De her omhandlede androstener med formel (I) har nyttig anvendelse som mellemprodukter ved fremstillingen af 20 17,17-bis-(substitueret thio)-3-ketoandrostener, der har antiinflammatorisk aktivitet.
Udtrykket "halogen" betegner, således som det er anvendt i hele beskrivelsen, enten individuelt eller som del af en større gruppe, fluor, chlor, brom og iod.
25 Den her omhandlede fremgangsmåde til fremstilling af androstenerne med formlen (I) er ejendommelig ved, at en forbindelse med den almene formel
I 2 S
30 R4 ^T'R3 (II) 35 *6
DK 164873 B
2 hvori R2, R3, R4, R5 og R6 har den ovenfor anførte betydning, omsættes med hydrogensulfid i nærværelse af en Lewis-syre ved en temperatur fra 0eC til -20°C.
Udgangsandrostenerne med formlen (II) kan fremstilles 5 ved omsætning af en androsten med formlen 10 (iii) i R6 15 hvori R^f R^/ Rg og Rg er som ovenfor defineret, med en thiol med formlen R2-SH, (IV) 20
hvori R2 er som ovenfor defineret, i nærværelse af en Lewis-syre (f.eks. bortrifluoridetherat), hvilket giver et steroid med formlen R R
2's _ s' 2 25 ,crv1(3 , Γ I (v)
^ ^5 T
30 R6 hvori R2, R^, R4, R^ og Rg er som ovenfor defineret.
Omsætningen kan gennemføres i et organisk opløsningsmiddel (f.eks. et halogeneret carbonhydrid) eller en blanding af organiske opløsningsmidler. Brugen 35 af iseddike som det eneste opløsningsmiddel eller i
DK 164873 B
3 blanding med andre opløsningsmidler forbedrer udbytterne. Reaktionsbetingelserne er ikke kritiske, og omsætningen kan hensigtsmæssigt gennemføres ved stuetemperatur, fortrinsvis i indifferent atmosfære (f.eks. argon eller nitrogen).
5 Der kan opnås gode udbytter med forholdsvis korte reaktionstider (på under 1 time). Tilsætning af en dimethyl-formamid-dialkylacetal (fortrinsvis dimethylformamid--dimethylacetal) forbedrer også udbytterne. Androstenen med formlen (V) opvarmes derpå i ren tilstand eller i et 10 indifferent opløsningsmiddel (f.eks. diethylbenzen eller dichlorbenzen), hvilket giver androstenen med formlen (II). Alternativt kan androstener med formlen (V) oxideres med en persyre (f.eks. m-chlorperbenzosyre) ved en temperatur fra ca. -78°C til ca. 0°C, idet det herved 15 fremkomne monosulfoxid opvarmes i et indifferent opløsningsmiddel, hvilket giver androstenen med formlen (II).
Til opnåelse af steroiderne med formlen (I) omsættes en androsten med formlen (II) med hydrogensulfid. Reaktionen gennemføres i nærværelse af Lewis-syre (f.eks. bortrifluorid-20 etherat) og gennemføres ved nedsat temperatur (dvs. mellem ca. 0 og ca. -20*C). Ved denne temperatur er omsætningen stereospecifik og giver det ønskede steroid med foralen (I).
Steroiderne med formlen (I) er nyttige mellemprodukter til fremstillingen af androstener med formlen 25 R«j R<7 2vS 7 ρ//Λ^Ν' 14 3 - (VII)
30 ^ RcJ
K
hvori R2, R3, R4, R5 og R6 har den ovenfor angivne betyd-35 ning, og R7 er alkyl. Således som beskrevet i US-patentskrift nr. 4.361.559 er steroiderne med formlen (VII) topiske,
DK 164873 B
4 antiflammatoriske midler, der kan anvendes til behandling af hudlidelser, såsom dermatitis, psoriasis, solforbrænding, eksem, neurodermatitis eller anogenital pruritus.
Et steroid med formlen (I) kan alkyleres under an-5 vendelse af konventionel teknik, hvilket giver det tilsvarende steroid med formlen (VII). Eksempler på alkylerings-teknik, som herved kan anvendes, er omsætningen af et steroid med formlen (I) (R7 = hydrogen i formel (VII)) med kalium-carbonat og et alkyliodid i nærværelse af en alkohol (f.eks.
10 methanol) og med kaliumcarbonat og substituerede alkylhaloge-nider i dimethylformamid.
Til yderligere belysning af den foreliggende opfindelse tjener følgende eksempel.
15 Eksempel 173-Ethylthio-9-f luor-llf3-hydroxy-17a-mercapto-androsta-1,4-dien-3-on_
En opløsning af 2,0 g 17-ethylthio-9-fluor-ll&--hydroxyandrosta-l,4,16-trien-3-on i 120 ml tørt dichlor- 20 methan afkøles og omrøres i et bad ved ca. -40°C, og en langsom strøm af hydrogensulfidgas sendes ind i opløsningen, medens der tilsættes 1,2 ml bortrifluorid-etherat. Efter ca. 3,5 til 4,0 timer fortyndes blandingen med chloroform, opvarmes til stuetemperatur og vaskes 25 efter hinanden med henholdsvis en fortyndet natriumbicarbonat-opløsning og vand. Opløsningen tørres, (vandfrit magnesiumsulfat), inddampes, og den faste remanens krystalliseres fra ethylacetat, hvorved fås 1,4 g af den i overskriften anførte forbindelse med smeltepunkt 239-242eC.
30 Den efterfølgende fremstilling illustrerer anvendelsen af forbindelsen fra eksemplet som mellemprodukt ved fremstilling af en terapeutisk aktiv androsten (formel (VII)).
35
DK 164873B
5
Fremstilling 17&-Ethylthio-9-fluor-113-hydroxy-17a-(methylthio)- androsta-1,4-dien-3-on_
En opløsning af 50 mg 173-ethylthio-9-fluor-5 -113“hydroxy-17a-mercaptoandrosta-l, 4-dien-3-on i 3,0 ml methanol og 3,0 ml tetrahydrofuran omrøres med 75 mg kaliumcarbonat og 0,3 ml methyliodid i 3,0 timer. Blandingen fortyndes derpå med vand, ekstraheres med chloroform, vaskes med vand, tørres (vandfrit magnesium-10 sulfat) og inddampes, hvilket giver et fast stof. En krystallisation af dette stof fra ethylacetat/hexan giver en analytisk prøve på 35 mg af den i overskriften anførte forbindelse, der har smeltepunkt 257-258°C.
Claims (1)
- 2. Fremgangsmåde til fremstilling af androstener med 20 den almene formel (I) ifølge krav 1, kendetegnet ved, at en forbindelse med den almene formel (II) R-I 2 s 25 rryV3 — (II) 30 hvor R2, R3, R4, R5 og Rg har den i krav 1 anførte betydning, omsættes med hydrogensulfid i nærværelse af en Lewis-syre ved en temperatur fra 0eC til -20°C. 35
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US41618182 | 1982-09-09 | ||
| US06/416,181 US4435326A (en) | 1982-09-09 | 1982-09-09 | Intermediates useful in the preparation of 17,17-bis(substituted thio)androstenes |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| DK407983D0 DK407983D0 (da) | 1983-09-08 |
| DK407983A DK407983A (da) | 1984-03-10 |
| DK164873B true DK164873B (da) | 1992-08-31 |
| DK164873C DK164873C (da) | 1993-01-11 |
Family
ID=23648912
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK407983A DK164873C (da) | 1982-09-09 | 1983-09-08 | 3-keto-17alfa-mercapto-17beta-(substitueret thio)-androstenderivater med anvendelse som mellemprodukter ved fremstillingen af 17,17-bis(substitueret thio)-3-ketoandrostener samt fremgangsmaade til deres fremstilling |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US4435326A (da) |
| EP (1) | EP0105224B1 (da) |
| JP (1) | JPS5967299A (da) |
| AT (1) | ATE25089T1 (da) |
| AU (1) | AU558201B2 (da) |
| CA (1) | CA1248087A (da) |
| DE (1) | DE3369326D1 (da) |
| DK (1) | DK164873C (da) |
| HU (2) | HU189744B (da) |
| IE (1) | IE55719B1 (da) |
| NO (1) | NO159602C (da) |
| ZA (1) | ZA836358B (da) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4529548A (en) * | 1984-05-07 | 1985-07-16 | E. R. Squibb & Sons, Inc. | 17β-(substituted thio)androstenes |
| US4529547A (en) * | 1984-06-20 | 1985-07-16 | E.R. Squibb & Sons, Inc. | 17-(substituted thio)-17-(substituted dithio)androstenes |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2949477A (en) * | 1959-03-04 | 1960-08-16 | Searle & Co | 1, 3, 17-triacetoxyestra-1, 3, 5(10), 16-tetraene and congeners |
| US4094840A (en) * | 1977-05-12 | 1978-06-13 | E. R. Squibb & Sons, Inc. | 17-Alkylthio (and arylthio) androsteno[16α,17α-b]benzodioxin-3-ones |
| US4091036A (en) * | 1977-05-12 | 1978-05-23 | E. R. Squibb & Sons, Inc. | 17-Alkylthio (and arylthio)-1',2',3',4'-tetrahydroandrosteno [16 α, 17 α-b]naphthalenes and derivatives |
| US4133811A (en) * | 1978-02-17 | 1979-01-09 | E. R. Squibb & Sons, Inc. | 13-Alkylthio (and arylthio)-11,17-epoxy-17-methyl-18-norandrostenes |
| US4146538A (en) * | 1978-02-27 | 1979-03-27 | E. R. Squibb & Sons, Inc. | 17-Alkylthio (and arylthio) androsteno[17α,16α-b]benzopyran-3-ones and [16α,17α]naphthopyran-3-ones |
| US4361559A (en) | 1981-08-20 | 1982-11-30 | E. R. Squibb & Sons, Inc. | Antiinflammatory 17,17-bis (substituted thio) androstenes |
-
1982
- 1982-09-09 US US06/416,181 patent/US4435326A/en not_active Expired - Fee Related
-
1983
- 1983-08-24 CA CA000435269A patent/CA1248087A/en not_active Expired
- 1983-08-25 AU AU18433/83A patent/AU558201B2/en not_active Ceased
- 1983-08-26 ZA ZA836358A patent/ZA836358B/xx unknown
- 1983-09-05 IE IE2080/83A patent/IE55719B1/en not_active IP Right Cessation
- 1983-09-08 JP JP58166447A patent/JPS5967299A/ja active Granted
- 1983-09-08 AT AT83108886T patent/ATE25089T1/de not_active IP Right Cessation
- 1983-09-08 EP EP83108886A patent/EP0105224B1/en not_active Expired
- 1983-09-08 HU HU833143A patent/HU189744B/hu not_active IP Right Cessation
- 1983-09-08 HU HU834616A patent/HU196432B/hu not_active IP Right Cessation
- 1983-09-08 DE DE8383108886T patent/DE3369326D1/de not_active Expired
- 1983-09-08 DK DK407983A patent/DK164873C/da not_active IP Right Cessation
- 1983-09-08 NO NO833208A patent/NO159602C/no unknown
Also Published As
| Publication number | Publication date |
|---|---|
| IE55719B1 (en) | 1991-01-02 |
| US4435326A (en) | 1984-03-06 |
| DK164873C (da) | 1993-01-11 |
| EP0105224A2 (en) | 1984-04-11 |
| AU1843383A (en) | 1984-03-15 |
| AU558201B2 (en) | 1987-01-22 |
| EP0105224B1 (en) | 1987-01-21 |
| DK407983A (da) | 1984-03-10 |
| JPH0439478B2 (da) | 1992-06-29 |
| CA1248087A (en) | 1989-01-03 |
| HU196432B (en) | 1988-11-28 |
| IE832080L (en) | 1984-03-09 |
| JPS5967299A (ja) | 1984-04-16 |
| HU189744B (en) | 1986-07-28 |
| EP0105224A3 (en) | 1984-08-01 |
| NO159602B (no) | 1988-10-10 |
| ATE25089T1 (de) | 1987-02-15 |
| ZA836358B (en) | 1984-04-25 |
| NO159602C (no) | 1989-01-18 |
| DK407983D0 (da) | 1983-09-08 |
| DE3369326D1 (en) | 1987-02-26 |
| NO833208L (no) | 1984-03-12 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PBP | Patent lapsed |