CH625810A5 - Process for the preparation of polyhalogenated steroids - Google Patents
Process for the preparation of polyhalogenated steroids Download PDFInfo
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- CH625810A5 CH625810A5 CH853980A CH853980A CH625810A5 CH 625810 A5 CH625810 A5 CH 625810A5 CH 853980 A CH853980 A CH 853980A CH 853980 A CH853980 A CH 853980A CH 625810 A5 CH625810 A5 CH 625810A5
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J7/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms
- C07J7/008—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms substituted in position 21
- C07J7/0085—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms substituted in position 21 by an halogen atom
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J21/00—Normal steroids containing carbon, hydrogen, halogen or oxygen having an oxygen-containing hetero ring spiro-condensed with the cyclopenta(a)hydrophenanthrene skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J31/00—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring
- C07J31/006—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring not covered by C07J31/003
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J5/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond
- C07J5/0046—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond substituted in position 17 alfa
- C07J5/0061—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond substituted in position 17 alfa substituted in position 16
- C07J5/0069—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond substituted in position 17 alfa substituted in position 16 by a saturated or unsaturated hydrocarbon group
- C07J5/0076—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond substituted in position 17 alfa substituted in position 16 by a saturated or unsaturated hydrocarbon group by an alkyl group
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J71/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
- C07J71/0005—Oxygen-containing hetero ring
- C07J71/001—Oxiranes
- C07J71/0015—Oxiranes at position 9(11)
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- Steroid Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
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2 2nd
PATENTANSPRÜCHE Die Erfindung betrifft ein Verfahren zur Herstellung von The invention relates to a method for producing
1. Verfahren zur Herstellung von neuen polyhalogenierten neuen polyhalogenierten Steroiden, und zwar von 9a, 21-Di- 1. Process for the preparation of new polyhalogenated new polyhalogenated steroids, namely from 9a, 21-di-
11 ß, 17a-Dihydroxy-16a-methyl-pregna-1,4-dien-3,20- halogen-11 ß, 17a-dihydroxy-6a-f luor-16a-methyl-pregna- 11β, 17a-dihydroxy-16a-methyl-pregna-1,4-diene-3.20-halogen-11ß, 17a-dihydroxy-6a-f luor-16a-methyl-pregna-
dion-17-estern der allgemeinen Formel l,4-dien-3,20-dion-17-estern der allgemeinen Formel dione-17-esters of the general formula l, 4-diene-3,20-dione-17-esters of the general formula
5 5
iH2X CH2X iH2X CH2X
- 04 - 04
.vi i"-0Ac .« p"r-0Ac .vi i "-0Ac.« p "r-0Ac
? \l/:\ / \ \ ^ xlyiv / \ / *. ? \ l /: \ / \ \ ^ xlyiv / \ / *.
T * PI • • • ••/-*!••• T * PI • • • •• / - *! •••
ì i Ì I ! Cl I CH_ ì i Ì I! Cl I CH_
" </VV 3 "</ VV 3
• (i) :• (i) • (i): • (i)
F F F F
worin X Brom oder Chlor und Ac eine von einer Carbonsäure abgeleitete Acylgruppe darstellt, dadurch gekennzeichnet, dass man eine Verbindung der allgemeinen Formel wherein X is bromine or chlorine and Ac is an acyl group derived from a carboxylic acid, characterized in that a compound of the general formula
OAc OAc
(II) (II)
worin Ac und X die oben angegebene Bedeutung haben, mit unterchloriger Säure oder einem unterchlorige Säure abgebenden Mittel behandelt. wherein Ac and X have the meaning given above, treated with hypochlorous acid or a hypochlorous acid releasing agent.
2. Verfahren nach Anspruch 1, dadurch gekennzeichnet, dass man mit t-Butylhypochlorit in Anwesenheit von Perchlorsäure behandelt. 2. The method according to claim 1, characterized in that treatment with t-butyl hypochlorite in the presence of perchloric acid.
3. Verfahren nach Anspruch 1 oder 2, dadurch gekennzeichnet, dass man eine Verbindung der Formel I herstellt, worin X für Chlor und Ac für den Acylrest einer niederaliphati-schen Monocarbonsäure mit 2 bis 7 Kohlenstoffatomen steht. 3. The method according to claim 1 or 2, characterized in that a compound of formula I is prepared, wherein X is chlorine and Ac is the acyl radical of a lower aliphatic monocarboxylic acid having 2 to 7 carbon atoms.
4. Verfahren gemäss einem der Ansprüche 1-3, dadurch gekennzeichnet, dass man eine Verbindung der Formel I herstellt, worin Ac für Propionyl steht. 4. The method according to any one of claims 1-3, characterized in that one produces a compound of formula I, wherein Ac is propionyl.
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In der Schweizerischen Patentschrift 621 801 wurden 2-Chlor-9a,21 -dihalogen-11 ß, 17a-dihydroxy-6a-fluor-16a-methylpregna-l,4-dien-3,20-dion-17-ester beschrieben, welche sich durch eine besonders günstige antiinflammatorische Wirksamkeit auszeichnen. Es wurde nun überraschenderweise festgestellt, dass dieselben günstigen pharmakologischen Eigenschaften auch bei den einfacheren, in der 2-Stellung unsubstitu-ierten Analogen auftreten. In the Swiss patent specification 621 801, 2-chloro-9a, 21 -dihalogen-11β, 17a-dihydroxy-6a-fluoro-16a-methylpregna-l, 4-diene-3,20-dione-17-ester were described, which are characterized by a particularly favorable anti-inflammatory activity. It has now surprisingly been found that the same favorable pharmacological properties also occur in the simpler analogues which are unsubstituted in the 2-position.
worin X Brom oder Chlor und Ac den Acylrest einer Carbonsäure darstellt. where X is bromine or chlorine and Ac is the acyl radical of a carboxylic acid.
Nachstehend mit «nieder» bezeichnete Kohlenstoffhaltige Verbindungen und Reste enthalten vorzugsweise bis und mit 7 Kohlenstoffatome. Carbon-containing compounds and radicals hereinafter referred to as “lower” preferably contain up to and including 7 carbon atoms.
Eine Acylgruppe Ac leitet sich vorzugweise von den in der Steroidchemie gebräuchlichen Carbonsäuren mit 1 bis 18 Kohlenstoffatomen, insbesondere von entsprechenden aliphatischen, cycloaliphatischen, cycloaliphatisch-aliphatischen, aromatischen oder araliphatischen Carbonsäuren ab. Der Rest Ac ist insbesondere ein geradkettiges oder verzweigtes Niederalk-anoyl, z.B. Acetyl, Propionyl, Butyryl, Isobutyryl, Valeryl, Iso-valeryl, Pivaloyl, 2-Aethyl-butyryl, 2,2- oder 3,3-Dimethyl-bu-tyryl, Hexanoyl oder Heptanoyl, aber auch ein Hydroxy-nieder-alkanoyl, z.B. 3-Hydroxypropionyl, Phenoxyniederalkanoyl, z.B. Phenoxyacetyl, Halogenniederalkanoyl, z.B. Chloracetyl, oder Carboxy-niederalkanoyl, z.B. 3-Carboxy-propionyl oder 4-Carboxy-butyryl, Alkenoyl, z.B. Undecylenoyl, Cycloalkyl-niederalkanoyl, z.B. Cyclopentyl-propionyl oder Cyclohexyl-acetyl, gegebenenfalls substituiertes Benzoyl, z.B. Benzoyl, oder gegebenenfalls substituiertes Phenylniederalkanoyl oder -nie-deralkenoyl, z.B. Phenylacetyl. An acyl group Ac is preferably derived from the carboxylic acids with 1 to 18 carbon atoms customary in steroid chemistry, in particular from corresponding aliphatic, cycloaliphatic, cycloaliphatic-aliphatic, aromatic or araliphatic carboxylic acids. The radical Ac is in particular a straight-chain or branched lower alkanoyl, e.g. Acetyl, propionyl, butyryl, isobutyryl, valeryl, iso-valeryl, pivaloyl, 2-ethyl-butyryl, 2,2- or 3,3-dimethyl-butyryl, hexanoyl or heptanoyl, but also a hydroxy-lower alkanoyl, e.g. 3-hydroxypropionyl, phenoxy lower alkanoyl, e.g. Phenoxyacetyl, halogeno lower alkanoyl e.g. Chloroacetyl, or carboxy-lower alkanoyl, e.g. 3-carboxy-propionyl or 4-carboxy-butyryl, alkenoyl, e.g. Undecylenoyl, cycloalkyl-lower alkanoyl, e.g. Cyclopentyl-propionyl or cyclohexyl-acetyl, optionally substituted benzoyl, e.g. Benzoyl, or optionally substituted phenyl-lower alkanoyl or non-deralkenoyl, e.g. Phenylacetyl.
Die erfindungsgemäss hergestellten Verbindungen besitzen wertvolle pharmakologische Eigenschaften. So zeichnen sie sich durch eine hervorragende antiinflammatorische Wirksamkeit, z.B. bei lokaler Anwendung, aus, die sich z.B. im Rohwattegra-nulomtest an der Ratte in einem Dosisbereich von etwa 0,001 bis etwa 0,3 mg/Pellet nachweisen lässt. Bei gleicher Versuchsanordnung sind die ersten Anzeichen einer systemischen Wirkung, z.B. die Abnahme des Körper- und insbesondere des Nebennieren- und Thymus-Gewichts, erst oberhalb der Dosis von 0,3 mg/Pellet bemerkbar. Wegen der günstigen Verteilung der biologischen Eigenschaften sind die neuen Verbindungen in allen Indikationen, für die sich Glucocorticoide mit entzündungshemmenden Eigenschaften eignen, insbesondere jedoch als lokal anzuwendende antiinflammatorische Glucocorticoide, z.B. zur Behandlung von entzündlichen Dermatosen, wie Ekzemen, Dermatiden, oder partiell corticoidresistenden Dermatosen, z.B. Psoriasis, verwendbar. Sie können zudem als wertvolle Zwischenprodukte zur Herstellung anderer nützlicher Stoffe, insbesondere anderer pharmakologisch wirksamer Steroide, Anwendung finden. The compounds produced according to the invention have valuable pharmacological properties. They are characterized by excellent anti-inflammatory effectiveness, e.g. with local application, which e.g. can be detected in the raw cotton wool test on the rat in a dose range from about 0.001 to about 0.3 mg / pellet. With the same experimental setup, the first signs of a systemic effect, e.g. the decrease in body and especially adrenal and thymus weight, only noticeable above the dose of 0.3 mg / pellet. Because of the favorable distribution of the biological properties, the new compounds are in all indications for which glucocorticoids with anti-inflammatory properties are suitable, but in particular as locally applicable anti-inflammatory glucocorticoids, e.g. for the treatment of inflammatory dermatoses, such as eczema, dermatids, or partially corticoid-resistant dermatoses, e.g. Psoriasis, usable. They can also be used as valuable intermediates for the production of other useful substances, in particular other pharmacologically active steroids.
Es betrifft in erster Linie Verbindungen der Formel I, worin X Chlor und Ac Niederalkanoyl, z.B. Propionyl, darstellt. It primarily relates to compounds of formula I, wherein X is chlorine and Ac lower alkanoyl, e.g. Propionyl.
Das erfindungsgemässe Verfahren ist dadurch gekennzeichnet, dass man eine Verbindung der allgemeinen Formel The process according to the invention is characterized in that a compound of the general formula
3 3rd
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ter Weise hergestellt werden, z.B. durch Abspalten von Wasser aus einem 6a-Fluor-llß,17a-dihydroxy-16a-methyl-21-X-pregna-l,4-dien-3,20-dion-17-ester, z.B. durch Behandeln mit einem geeigneten Säurechlorid, wie Phosphoroxychlorid oder OAc 5 Methansulfonsäurechlorid, in Gegenwart einer Base, z.B. Pyri din. way, e.g. by splitting off water from a 6a-fluoro-11ß, 17a-dihydroxy-16a-methyl-21-X-pregna-l, 4-diene-3,20-dione-17-ester, e.g. by treatment with a suitable acid chloride such as phosphorus oxychloride or OAc 5 methanesulfonic acid chloride in the presence of a base, e.g. Pyri din.
Die gemäss der vorliegenden Erfindung hergestellten neuen Verbindungen der Formel I finden Verwendung als medizinische Wirkstoffe, vorzugsweise zur Behandlung von Entzündun-10 gen, in erster Linie als lokal anzuwendende antiinflammatori-p (II) sehe Glucocorticoide, üblicherweise in Form von pharmazeuti schen Präparaten, insbesondere solchen zur topischen Anwen-worin X und Ac die oben angegebenen Bedeutungen haben, mit dung. The new compounds of the formula I produced according to the present invention are used as medicinal active substances, preferably for the treatment of inflammations, primarily as locally applicable antiinflammatori-p (II) see glucocorticoids, usually in the form of pharmaceutical preparations, in particular those for topical use in which X and Ac have the meanings given above, with dung.
unterchloriger Säure oder einem unterchlorige Säure abgeben- Das nachfolgende Beispiel illustriert die oben beschriebene den Mittel behandelt. 15 Erfindung ohne sie jedoch in ihrem Umfang in irgend einer Hypochlorous acid or a hypochlorous acid release- The following example illustrates the agent described above. 15 invention without it however in its scope in any one
Gemäss obigem Verfahren werden an die 9,11-Doppelbin- Weise einzuschränken. Temperaturen werden in Celsiusgraden dung der Ausgangsstoffe der Formel II in an sich bekannter angegeben. According to the above procedure, the 9.11 double bin mode is to be restricted. Temperatures are given in degrees Celsius of the starting materials of the formula II in a manner known per se.
Weise die Elemente der unterchlorigen Säure angelagert. Dabei arbeitet man z.B. mit wässriger unterchloriger Säure, oder man Beispiel kann ein die unterchlorige Säure abgebendes Mittel, wie ein 20 Eine gerührte Lösung von 3,8 g 21-Chlor-6a-fluor-17a-N-Chlor-carbonsäureamid oder -imid (vgl. US-Patentschrift hydroxy-16a-methyl-pregna-l,4,9 (1 l)-trien-3,20-dion-17-3 057 886) verwenden. Die Reaktion führt man in einem iner- propionat in 76 ml t-Butylalkohol wird unter Stickstoff nacheinten Lösungsmittel, wie einem tertiären Alkohol, z.B. tert.-But- ander mit 4,95 ml einer 10%-igen Perchlorsäurelösung und anol, einem Äther, z.B. Diäthyläther, Methylisopropyläther, 1,49 ml t-Butylhypochlorit versetzt. Nach 3,5 Stunden weiterem Dioxan oder Tetrahydrofuran, oder einem Keton, z.B. Aceton, 25 Rühren wird das Gemisch auf Eiswasser unter Rühren gegossen in Gegenwart von Wasser und gegebenenfalls einer starken Säu- und in Chloroform aufgenommen. Die organische Phase wird re, durch. nacheinander mit einer 10%-igen Kaliumjodidlösung, 10%- Way the elements of hypochlorous acid accumulated. One works e.g. with aqueous hypochlorous acid, or an example can be a hypochlorous acid releasing agent, such as a 20 A stirred solution of 3.8 g of 21-chloro-6a-fluoro-17a-N-chloro-carboxylic acid amide or imide (cf. Patent specification hydroxy-16a-methyl-pregna-l, 4.9 (1 l) -triene-3.20-dione-17-3 057 886) use. The reaction is carried out in an in-propionate in 76 ml of t-butyl alcohol, a solvent, such as a tertiary alcohol, e.g. tert-butane with 4.95 ml of a 10% perchloric acid solution and anol, an ether, e.g. Diethyl ether, methyl isopropyl ether, 1.49 ml of t-butyl hypochlorite added. After another 3.5 hours of dioxane or tetrahydrofuran, or a ketone, e.g. Acetone, stirring, the mixture is poured onto ice water with stirring in the presence of water and, if appropriate, a strong acid and in chloroform. The organic phase becomes re through. successively with a 10% potassium iodide solution, 10% -
Die Anlagerung der unterchlorigen Säure an die 9,11-Dop- igen Natriumthiosulfatlösung und verdünnter eiskalter Natron-pelbindung des Ausgangsmaterials der Formel II kann auch in lauge gewaschen, über Natriumsulfat getrocknet und im Vaku-nicht-wässrigem Medium erfolgen. Eine besonders vorteilhafte 30 um eingedampft. Das erhaltene amorphe Rohprodukt wird über Ausführungsform dieser Modifikation stellt die Verwendung eine 30-fache Gewichtsmenge Silicagel chromatographiert. von Niederalkylhypochloriten, in erster Linie von tert.-Butylhy- Durch Eluieren mit einem Gemisch von Toluol-Aceton (90:10) pochlorit, in einem inerten, mit Wasser nicht mischbaren Lö- werden Fraktionen erhalten, die nach Eindampfen und Besprit-sungsmittel, wie z.B. einem Nitrokohlenwasserstoff, üblicher- zen mit Äther kristallin erstarren. Durch Umlösen aus Acetonweise in Gegenwart von Perchlorsäure dar (vgl. Deutsche Pa- 35 Hexan resultiert das 9a, 21-Dichlor-6a-fluor-l lß,17a-di-tentschrift2 011 559). hydroxy-16a-methyl-pregna-l,4-dien-3,20-dion-17-propio- The addition of hypochlorous acid to the 9.11-dopene sodium thiosulfate solution and dilute ice-cold sodium pelbinding of the starting material of the formula II can also be washed in brine, dried over sodium sulfate and carried out in a vacuum-non-aqueous medium. A particularly advantageous 30 µm evaporated. The obtained amorphous crude product is chromatographed over the embodiment of this modification, the use represents a 30-fold amount by weight of silica gel. of lower alkyl hypochlorites, primarily of tert-butyl hy- By elution with a mixture of toluene-acetone (90:10) pochlorite, in an inert, water-immiscible solvent, fractions are obtained which, after evaporation and spray, such as a nitro-hydrocarbon, usually solidify with ether crystalline. By redissolving from acetone in the presence of perchloric acid (see German Pa-35 hexane results in 9a, 21-dichloro-6a-fluoro-lß, 17a-dentschrift 2,011,559). hydroxy-16a-methyl-pregna-l, 4-diene-3,20-dione-17-propio-
Die Ausgangsstoffe der Formel II können in an sich bekann- nat, Smp. 267-268 °. The starting materials of the formula II can be known per se, mp. 267-268 °.
C C.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| LU75903A LU75903A1 (en) | 1976-09-29 | 1976-09-29 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH625810A5 true CH625810A5 (en) | 1981-10-15 |
Family
ID=19728370
Family Applications (9)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH1549976A CH624967A5 (en) | 1976-09-29 | 1976-12-09 | Process for the preparation of polyhalogenated steroids |
| CH1172177A CH632279A5 (en) | 1976-09-29 | 1977-09-26 | Process for the preparation of polyhalogenated steroids |
| CH853780A CH625808A5 (en) | 1976-09-29 | 1980-11-18 | Process for the preparation of polyhalogenated steroids |
| CH853980A CH625810A5 (en) | 1976-09-29 | 1980-11-18 | Process for the preparation of polyhalogenated steroids |
| CH853880A CH625809A5 (en) | 1976-09-29 | 1980-11-18 | Process for the preparation of polyhalogenated steroids |
| CH683281A CH632000A5 (en) | 1976-09-29 | 1981-10-26 | Process for the preparation of polyhalogenated steroids |
| CH683181A CH631999A5 (en) | 1976-09-29 | 1981-10-26 | Process for the preparation of polyhalogenated steroids |
| CH683081A CH631998A5 (en) | 1976-09-29 | 1981-10-26 | Process for the preparation of polyhalogenated steroids |
| CH4682A CH632521A5 (en) | 1976-09-29 | 1982-01-06 | Process for the preparation of polyhalogenated steroids |
Family Applications Before (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH1549976A CH624967A5 (en) | 1976-09-29 | 1976-12-09 | Process for the preparation of polyhalogenated steroids |
| CH1172177A CH632279A5 (en) | 1976-09-29 | 1977-09-26 | Process for the preparation of polyhalogenated steroids |
| CH853780A CH625808A5 (en) | 1976-09-29 | 1980-11-18 | Process for the preparation of polyhalogenated steroids |
Family Applications After (5)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH853880A CH625809A5 (en) | 1976-09-29 | 1980-11-18 | Process for the preparation of polyhalogenated steroids |
| CH683281A CH632000A5 (en) | 1976-09-29 | 1981-10-26 | Process for the preparation of polyhalogenated steroids |
| CH683181A CH631999A5 (en) | 1976-09-29 | 1981-10-26 | Process for the preparation of polyhalogenated steroids |
| CH683081A CH631998A5 (en) | 1976-09-29 | 1981-10-26 | Process for the preparation of polyhalogenated steroids |
| CH4682A CH632521A5 (en) | 1976-09-29 | 1982-01-06 | Process for the preparation of polyhalogenated steroids |
Country Status (24)
| Country | Link |
|---|---|
| JP (1) | JPS5356652A (en) |
| AT (3) | AT363197B (en) |
| AU (1) | AU514200B2 (en) |
| BE (1) | BE859120A (en) |
| CA (1) | CA1101410A (en) |
| CH (9) | CH624967A5 (en) |
| CY (1) | CY1178A (en) |
| DD (1) | DD133150A5 (en) |
| DE (1) | DE2743069A1 (en) |
| DK (1) | DK146017C (en) |
| ES (1) | ES462763A1 (en) |
| FR (1) | FR2366311A1 (en) |
| GB (1) | GB1563638A (en) |
| HK (1) | HK16683A (en) |
| HU (1) | HU175218B (en) |
| IE (1) | IE46047B1 (en) |
| IL (1) | IL53012A (en) |
| KE (1) | KE3258A (en) |
| LU (1) | LU75903A1 (en) |
| MY (1) | MY8400092A (en) |
| NL (1) | NL7710089A (en) |
| SE (1) | SE436751B (en) |
| SG (1) | SG3383G (en) |
| ZA (1) | ZA775800B (en) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL187577C (en) * | 1978-04-05 | 1991-11-18 | Sibla Srl | 3-ACETOXY-9BETA, 11BETA-EPOXY-PREGNA-1,3,5-TRIEN, PROCESS FOR THE PREPARATION THEREOF, AND PROCESS FOR THE PREPARATION OF 6-alpha-halogen-1,4-diene-3-ones. |
| DE3227312A1 (en) * | 1982-07-19 | 1984-01-19 | Schering AG, 1000 Berlin und 4709 Bergkamen | NEW 6.16 DIMETHYL CORTICOIDS, THEIR PRODUCTION AND USE |
| EP0523132A1 (en) * | 1990-03-27 | 1993-01-20 | Schering Corporation | PROCESS FOR 9$g(a)-HYDROXY STEROID DEHYDRATION |
| US5972922A (en) * | 1990-06-11 | 1999-10-26 | Alcon Laboratories, Inc. | Steroids which inhibit angiogenesis |
| MXPA04005188A (en) | 2001-11-29 | 2004-08-11 | Taro Pharma Ind | Method for the production of 6-alpha-fluoro corticosteroids. |
| US8809307B2 (en) | 2010-11-22 | 2014-08-19 | Dow Pharmaceutical Sciences, Inc. | Pharmaceutical formulations containing corticosteroids for topical administration |
| US11957753B2 (en) | 2010-11-22 | 2024-04-16 | Bausch Health Ireland Limited | Pharmaceutical formulations containing corticosteroids for topical administration |
| ES2812451T3 (en) | 2015-06-18 | 2021-03-17 | Bausch Health Ireland Ltd | Topical compositions comprising a corticosteroid and a retinoid to treat psoriasis |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB898292A (en) * | 1959-03-18 | 1962-06-06 | Upjohn Co | Improvements in or relating to steroids and the manufacture thereof |
| US3644340A (en) * | 1970-03-19 | 1972-02-22 | Syntex Corp | Preparation of 21-chloro steroids |
| US3992422A (en) * | 1975-08-14 | 1976-11-16 | Schering Corporation | Process for the preparation of 21-halogeno-21-desoxy-17α-acyloxy-20-keto-pregnenes |
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1976
- 1976-09-29 LU LU75903A patent/LU75903A1/xx unknown
- 1976-12-09 CH CH1549976A patent/CH624967A5/en not_active IP Right Cessation
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1977
- 1977-06-08 SE SE7706673A patent/SE436751B/en not_active IP Right Cessation
- 1977-06-09 DK DK256977A patent/DK146017C/en not_active IP Right Cessation
- 1977-09-14 NL NL7710089A patent/NL7710089A/en not_active Application Discontinuation
- 1977-09-24 DE DE19772743069 patent/DE2743069A1/en active Granted
- 1977-09-26 CH CH1172177A patent/CH632279A5/en not_active IP Right Cessation
- 1977-09-27 FR FR7729043A patent/FR2366311A1/en active Granted
- 1977-09-27 CA CA287,560A patent/CA1101410A/en not_active Expired
- 1977-09-27 GB GB40131/77A patent/GB1563638A/en not_active Expired
- 1977-09-27 AU AU29148/77A patent/AU514200B2/en not_active Expired
- 1977-09-27 CY CY1178A patent/CY1178A/en unknown
- 1977-09-27 DD DD7700201226A patent/DD133150A5/en unknown
- 1977-09-28 IL IL53012A patent/IL53012A/en unknown
- 1977-09-28 ZA ZA00775800A patent/ZA775800B/en unknown
- 1977-09-28 IE IE1979/77A patent/IE46047B1/en not_active IP Right Cessation
- 1977-09-28 HU HU77CI1774A patent/HU175218B/en unknown
- 1977-09-28 BE BE181243A patent/BE859120A/en not_active IP Right Cessation
- 1977-09-28 AT AT0691077A patent/AT363197B/en not_active IP Right Cessation
- 1977-09-29 JP JP11619377A patent/JPS5356652A/en active Granted
- 1977-09-29 ES ES462763A patent/ES462763A1/en not_active Expired
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1979
- 1979-02-28 AT AT0151279A patent/AT363202B/en not_active IP Right Cessation
- 1979-02-28 AT AT0151379A patent/AT363203B/en not_active IP Right Cessation
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1980
- 1980-11-18 CH CH853780A patent/CH625808A5/en not_active IP Right Cessation
- 1980-11-18 CH CH853980A patent/CH625810A5/en not_active IP Right Cessation
- 1980-11-18 CH CH853880A patent/CH625809A5/en not_active IP Right Cessation
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1981
- 1981-10-26 CH CH683281A patent/CH632000A5/en not_active IP Right Cessation
- 1981-10-26 CH CH683181A patent/CH631999A5/en not_active IP Right Cessation
- 1981-10-26 CH CH683081A patent/CH631998A5/en not_active IP Right Cessation
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1982
- 1982-01-06 CH CH4682A patent/CH632521A5/en not_active IP Right Cessation
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1983
- 1983-01-20 SG SG33/83A patent/SG3383G/en unknown
- 1983-01-21 KE KE3258A patent/KE3258A/en unknown
- 1983-05-19 HK HK166/83A patent/HK16683A/en not_active IP Right Cessation
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1984
- 1984-12-30 MY MY92/84A patent/MY8400092A/en unknown
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PL | Patent ceased |