CH625808A5 - Process for the preparation of polyhalogenated steroids - Google Patents
Process for the preparation of polyhalogenated steroids Download PDFInfo
- Publication number
- CH625808A5 CH625808A5 CH853780A CH853780A CH625808A5 CH 625808 A5 CH625808 A5 CH 625808A5 CH 853780 A CH853780 A CH 853780A CH 853780 A CH853780 A CH 853780A CH 625808 A5 CH625808 A5 CH 625808A5
- Authority
- CH
- Switzerland
- Prior art keywords
- alpha
- dione
- chlorine
- dihydroxy
- methyl
- Prior art date
Links
Classifications
-
- 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
-
- 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
-
- 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)
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Pain & Pain Management (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Rheumatology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Steroid Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
625 808 625 808
2 2nd
PATENTANSPRÜCHE 1. Verfahren zur Herstellung von neuen polyhalogenierten ll/tf,17a-Dihydroxy-16a-methyl-pregna-l,4-dien-3,20-dion-17-estern der allgemeinen Formel PATENT CLAIMS 1. Process for the preparation of new polyhalogenated ll / tf, 17a-dihydroxy-16a-methyl-pregna-l, 4-diene-3,20-dione-17-esters of the general formula
H0x /vT3 f 0A H0x / vT3 f 0A
• « » •.. • OAc • «» • .. • OAc
Wirksamkeit auszeichnen. Es wurde nun überraschenderweise festgestellt, dass dieselben günstigen pharmakologischen Eigenschaften auch bei den einfacheren, in der 2-Stellung unsubstituierten Analogen auftreten. Award effectiveness. 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.
Die Erfindung betrifft ein Verfahren zur Herstellung von neuen polyhalogenierten Steroiden, und zwar von 9a,21-Di-halogen-ll/?,17tt-dihydroxy-6a-fluor-16«-methyl-pregna-l,4-dien-3,20-dion-17-estern der allgemeinen Formel The invention relates to a process for the preparation of new polyhalogenated steroids, namely of 9a, 21-di-halogen-ll /?, 17tt-dihydroxy-6a-fluoro-16 «-methyl-pregna-l, 4-dien-3, 20-dione-17-esters of the general formula
(I) (I)
CH. CH.
io io
15 15
. W i l . W i l
S \l/:\ / \ / \ S \ l /: \ / \ / \
• • w • • • • w • •
i i M i i M
v \/ v \ /
•i • i
F F
worin Xi Chlor oder Fluor, X2 Brom oder Chlor, und Ac eine von einer Carbonsäure abgeleitete Acylgruppe darstellt, 20 dadurch gekennzeichnet, dass man eine 1,2-gesättigte Verbindung der allgemeinen Formel wherein Xi represents chlorine or fluorine, X2 bromine or chlorine, and Ac represents an acyl group derived from a carboxylic acid, 20 characterized in that a 1,2-saturated compound of the general formula
*2*2 * 2 * 2
\ / \ .«pi ! . \ / \. «Pi! .
^ \l/:\ ✓ \ / *. ^ \ l /: \ ✓ \ / *.
a A A a A A
• y • • y •
I *11 I * 11
/vV / vV
• • • OAc • • • OAc
CH„ CH "
(I) (I)
»,/.fi. .fi ! i », /. Fi. .fi! i
/ \l/:\ / \ / / \ l /: \ / \ /
I I.
OAc OAc
(II) (II)
25 25th
30 30th
I Xll I Xll
CH. CH.
35 35
worin Ac, Xi und X2 die oben angegebenen Bedeutungen haben, dehydriert. wherein Ac, Xi and X2 have the meanings given above, dehydrated.
2. Verfahren nach Anspruch 1, dadurch gekennzeichnet, dass man mit einem dehydrierenden Chinon dehydriert. 2. The method according to claim 1, characterized in that dehydrated with a dehydrating quinone.
3. Verfahren nach Anspruch 1, dadurch gekennzeichnet, 40 dass man mit 2,3-Dichlor-5,6-dicyano-l,4-benzochinon dehydriert. 3. The method according to claim 1, characterized in that 40 is dehydrogenated with 2,3-dichloro-5,6-dicyano-l, 4-benzoquinone.
4. Verfahren nach einem der Ansprüche 1—3, dadurch gekennzeichnet, dass man eine Verbindung der Formel I herstellt, worin Xi für Chlor oder Fluor, X2 für Chlor und Ac 45 für den Acylrest einer niederaliphatischen Monocarbonsäure mit 2 bis 7 Kohlenstoffatomen steht. 4. The method according to any one of claims 1-3, characterized in that a compound of formula I is prepared, wherein Xi is chlorine or fluorine, X2 for chlorine and Ac 45 for the acyl radical of a lower aliphatic monocarboxylic acid having 2 to 7 carbon atoms.
5. Verfahren gemäss einem der Ansprüche 1—3, dadurch gekennzeichnet, dass man eine Verbindung der Formel I herstellt, worin Ac für Propionyl steht. 5. The method according to any one of claims 1-3, characterized in that one produces a compound of formula I, wherein Ac is propionyl.
6. Verfahren nach einem der Ansprüche 1—3, dadurch gekennzeichnet, dass man 21-Chlor-6a,9a-difluor-ll/?,17a-di-hydroxy-16a-methyl-pregna-l,4-dien-3,20-dion-17-propionat herstellt. 6. The method according to any one of claims 1-3, characterized in that 21-chloro-6a, 9a-difluoro-II /?, 17a-di-hydroxy-16a-methyl-pregna-l, 4-diene-3, 20-dione-17-propionate.
7. Verfahren nach einem der Ansprüche 1—3, dadurch gekennzeichnet, dass man 21-Chlor-6a,9a-difluor-ll/?,17a-di-hydroxy-16a-methyl-pregna-l,4-dien-3,20-dion-17-acetat herstellt. 7. The method according to any one of claims 1-3, characterized in that 21-chloro-6a, 9a-difluoro-ll /?, 17a-di-hydroxy-16a-methyl-pregna-l, 4-diene-3, Produces 20-dione-17-acetate.
8. Verfahren nach einem der Ansprüche 1—3, dadurch gekennzeichnet; dass man 21-Chlor-6a,9a-difluor-ll/?,17a-di-hydroxy-16a-methyl-pregna-l,4-dien-3,20-dion-17-valerianat herstellt. 8. The method according to any one of claims 1-3, characterized; that 21-chloro-6a, 9a-difluoro-II /?, 17a-di-hydroxy-16a-methyl-pregna-l, 4-diene-3,20-dione-17-valerianate is produced.
50 50
55 55
60 60
In der schweizerischen Patentschrift 621 801 wurden 2-Chlor-9a,21 -dihalogen-1 lß, 17a-dihydroxy-6a-fluor- 16a-methylpregna-l,4-dien-3,20-dion-17-ester beschrieben, welche sich durch eine besonders günstige antiinflammatorische Swiss Patent 621,801 describes 2-chloro-9a, 21-dihalogen-1ß, 17a-dihydroxy-6a-fluoro-16a-methylpregna-l, 4-diene-3,20-dione-17-ester, which are distinguishes itself through a particularly favorable anti-inflammatory
65 65
worin Xi Chlor oder Fluor, X2 Brom oder Chlor und Ac den Acylrest einer Carbonsäure darstellt. wherein Xi represents chlorine or fluorine, X2 bromine or chlorine and Ac represents 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 vorzugsweise 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 Nie-deralkanoyl, z. B. Acetyl, Propionyl, Butyryl, Isobutyryl, Va-leryl, Isovaleryl, Pivaloyl, 2-Äthyl-butyryl, 2,2- oder 3,3-Di-methyl-butyryl, Hexanoyl oder Heptanoyl, aber auch ein Hydroxyniederalkanoyl, z. B. 3-Hydroxypropionyl, Phenoxy-niederalkanoyl, z. B. Phenoxyacetyl, Halogenniederalkanoyl, z. B. Chloracetyl, oder Carboxyniederalkanoyl, z. B. 3-Carb-oxy-propionyl oder 4-Carboxy-butyryl, Alkenoyl, z. B. Un-decylenoyl, Cycloalkylniederalkanoyl, z. B. Cyclopentyl-propionyl oder Cyclohexylacetyl, gegebenenfalls substituiertes Benzoyl, z. B. Benzoyl, oder gegebenenfalls substituiertes Phenylniederalkanoyl oder -niederalkenoyl, z. B. Phenyl-acetyl. 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 rest Ac is in particular a straight-chain or branched lower alkanoyl, e.g. B. acetyl, propionyl, butyryl, isobutyryl, Va-leryl, isovaleryl, pivaloyl, 2-ethyl-butyryl, 2,2- or 3,3-dimethyl-butyryl, hexanoyl or heptanoyl, but also a hydroxyniederalkanoyl, e.g. B. 3-hydroxypropionyl, phenoxy-lower alkanoyl, e.g. B. phenoxyacetyl, halogen-lower alkanoyl, e.g. B. chloroacetyl, or carboxy lower alkanoyl, e.g. B. 3-carboxy-propionyl or 4-carboxy-butyryl, alkenoyl, e.g. B. Un-decylenoyl, cycloalkyl-lower alkanoyl, e.g. B. cyclopentyl-propionyl or cyclohexylacetyl, optionally substituted benzoyl, e.g. B. benzoyl, or optionally substituted phenyl-lower alkanoyl or lower alkenoyl, e.g. B. phenyl acetyl.
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 Rohwattegranulomtest 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 Glu-cocorticoide mit entzündungshemmenden Eigenschaften eignen, insbesondere jedoch als lokal anzuwendende antiinflammatorische Glucocorticoide, z. B. zur Behandlung von entzündlichen Dermatosen, wie Ekzemen, Dermatiden, oder partiell corticoidresistenten 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. So they are characterized by an excellent anti-inflammatory activity, for. B. in local application, z. B. in the raw cotton granuloma 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. B. 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 glu-cocorticoids with anti-inflammatory properties are suitable, but in particular as locally applicable anti-inflammatory glucocorticoids, e.g. B. for the treatment of inflammatory dermatoses, such as eczema, dermatids, or partially corticoid-resistant dermatoses, for. B. psoriasis, can be used. 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 Xi Fluor oder Chlor, X2 Chlor, und Ac Niederalka-noyl, z. B. Propionyl, darstellt. It primarily relates to compounds of the formula I in which Xi is fluorine or chlorine, X2 is chlorine, and Ac Niederalka-noyl, e.g. B. propionyl.
3 3rd
625 808 625 808
Das erfindungsgemässe Verfahren ist dadurch gekennzeichnet, dass man eine 1,2-gesättigte Verbindung der allgemeinen Formel The process according to the invention is characterized in that a 1,2-saturated compound of the general formula
\ / \ . <fi i . \ / \. <fi i.
' \l/:\ / \ / % '\ l /: \ / \ /%
• . OAc •. OAc
(II) (II)
1 i Hi 1 i Hi
«/ V V «/ V V
10 10th
worin Xi, X2 und Ac die oben angegebenen Bedeutungen haben, dehydriert. wherein Xi, X2 and Ac have the meanings given above, dehydrated.
Die Dehydrierung kann z. B. durch Behandeln mit einem geeigneten dehydrierenden Chinon, wie 2,3-Dichlor-5,6-di-cyano-l,4-benzochinon, durchgeführt werden. The dehydration can e.g. B. by treatment with a suitable dehydrating quinone, such as 2,3-dichloro-5,6-di-cyano-l, 4-benzoquinone.
Die 1,2-Dehydrierung von Ausgangsstoffen der Formel II kann auch durch Behandeln mit Selendioxyd oder mikrobiologisch, z. B. mit geeigneten Mikroorganismen, wie Coryne-bacterium simplex oder Septomyxa affinis, erfolgen. The 1,2-dehydrogenation of starting materials of the formula II can also be carried out by treatment with selenium dioxide or microbiologically, e.g. B. with suitable microorganisms such as Coryne bacterium simplex or Septomyxa affinis.
Die Ausgangsstoffe der Formel II kann man durch Überführen der 21-Hydroxylgruppe in einem 6a-Fluor-ll/?,17a,21-trihydroxy-16a-methyl-9a-Xi-pregn-4-en-3,20-dion-17-ester, durch Behandeln mit einem geeigneten Sulfonsäurederivat, wie Methansulfonsäurechlorid in eine 21-organische Sulfonyl-oxygruppe und Behandeln des Zwischenproduktes mit einem Lithiumhalogenid, z. B. Lithiumchlorid, erhalten. The starting materials of the formula II can be converted into a 6a-fluoro-II /?, 17a, 21-trihydroxy-16a-methyl-9a-Xi-pregn-4-en-3,20-dione-17 by converting the 21-hydroxyl group -ester, by treatment with a suitable sulfonic acid derivative, such as methanesulfonic acid chloride in a 21-organic sulfonyloxy group and treating the intermediate with a lithium halide, e.g. B. lithium chloride obtained.
Die gemäss der vorliegenden Erfindung hergestellten neuen Verbindungen der Formel I finden Verwendung als medizinische Wirkstoffe, vorzugsweise zur Behandlung von Entzündungen, in erster Linie als lokal anzuwendende antiinflammatorische Glucocorticoide, üblicherweise in Form von pharmazeutischen Präparaten, insbesondere solchen zur topischen Anwendung. The new compounds of the formula I prepared according to the present invention are used as medicinal active substances, preferably for the treatment of inflammation, primarily as locally applicable anti-inflammatory glucocorticoids, usually in the form of pharmaceutical preparations, in particular those for topical use.
Die nachfolgenden Beispiele illustrieren die oben be15 The following examples illustrate the be15 above
20 20th
25 25th
30 30th
35 35
schriebene Erfindung; sie sollen jedoch diese in ihrem Umfang in keiner Weise einschränken. Temperaturen werden in Celsiusgraden angegeben. written invention; however, they are not intended to limit their scope in any way. Temperatures are given in degrees Celsius.
Beispiel 1 example 1
Eine Lösung von 230 mg 21-Chlor-6a,9a-difluor-ll/?,17a-dihydroxy-16a-methyl-pregn-4-en-3,20-dion-17-propionat in 1,9 ml Dioxan wird nach Zugabe von 230 mg 2,3-Dichlor-5,6-dicyano-l,4-benzochinon (DDQ) während 20 Stunden in einer Stickstoffatmosphäre am Rückfluss gekocht. Nach dem Eindampfen im Wasserstrahlvakuum wird der amorphe Rückstand an lOOfacher Gewichtsmenge Kieselgel (Stufensäule) Chromatographien. Die mit Methylenchlorid-Methanol-(99:1)-Gemisch eluierten Fraktionen ergeben das 21-Chlor-6a,9a-difluor-ll/?,17a-dihydroxy-16a-methyl-pregna-l,4-dien-3,20-dion-17-propionat, das nach Umkristallisieren aus einem Gemisch von Chloroform, Methanol und Diäthyläther bei 268° (Zers.) schmilzt. A solution of 230 mg of 21-chloro-6a, 9a-difluoro-II /?, 17a-dihydroxy-16a-methyl-pregn-4-en-3,20-dione-17-propionate in 1.9 ml of dioxane is followed Add 230 mg of 2,3-dichloro-5,6-dicyano-l, 4-benzoquinone (DDQ) boiled under reflux for 20 hours in a nitrogen atmosphere. After evaporation in a water-jet vacuum, the amorphous residue is chromatographed on 100 times the amount by weight of silica gel (step column). The fractions eluted with methylene chloride-methanol (99: 1) mixture give 21-chloro-6a, 9a-difluoro-11 /?, 17a-dihydroxy-16a-methyl-pregna-l, 4-diene-3.20 -dione-17-propionate, which melts after recrystallization from a mixture of chloroform, methanol and diethyl ether at 268 ° (dec.).
In analoger Weise, aber ausgehend vom entsprechenden 9a-Chloranalogen wird das 9a,21-Dichlor-6a-fluor-ll/S,17a-dihydroxy-16a-methyl-pregna-l,4-dien-3,20-dion-17-propio-nat, Smp. 267—268°, erhalten. In an analogous manner, but starting from the corresponding 9a-chlorine analogue, 9a, 21-dichloro-6a-fluoro-II / S, 17a-dihydroxy-16a-methyl-pregna-1,4, 4-diene-3,20-dione-17 -propio-nat, mp. 267-268 °.
Beispiel 2 Example 2
In der im Beispiel 1 beschriebenen Weise wird 640 mg 21-Chlor-6a,9a-difluor-ll/?,17a-dihydroxy-16a-methyl-pregn-4-en-3,20-dion-17-acetat in 3,9 ml Dioxan mit 640 mg DDQ behandelt und weiterverarbeitet. Es resultiert 21-Chlor-6a,9a-difluor-ll/j,17a-dihydroxy-16a-methyl-pregna-l,4-dien-3,20-dion-17-acetat, Smp. 269—271°. In the manner described in Example 1, 640 mg of 21-chloro-6a, 9a-difluoro-II /?, 17a-dihydroxy-16a-methyl-pregn-4-en-3,20-dione-17-acetate in 3, 9 ml of dioxane treated with 640 mg DDQ and processed. The result is 21-chloro-6a, 9a-difluoro-11 / j, 17a-dihydroxy-16a-methyl-pregna-l, 4-diene-3,20-dione-17-acetate, mp. 269-271 °.
Beispiel 3 Example 3
In der im Beispiel 1 beschriebenen Weise wird 845 mg 21-Chlor-6a,9a-difluor-ll/S,17a-dihydroxy-16a-methyl-pregn-4-en-3,20-dion-17-valerianat in 5,2 ml Dioxan mit 845 mg DDQ behandelt und weiterverarbeitet. Es resultiert 21-Chlor-6a,9a-difluor-ll/?,17a-dihydroxy-16a-methyl-pregna-l,4-dien-3,20-dion-17-valerianat, Smp. 244—245°. In the manner described in Example 1, 845 mg of 21-chloro-6a, 9a-difluoro-II / S, 17a-dihydroxy-16a-methyl-pregn-4-en-3,20-dione-17-valerianate in 5, 2 ml of dioxane treated with 845 mg DDQ and processed. The result is 21-chloro-6a, 9a-difluoro-II /?, 17a-dihydroxy-16a-methyl-pregna-l, 4-diene-3,20-dione-17-valerianate, mp. 244-245 °.
M M
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 |
|---|---|
| CH625808A5 true CH625808A5 (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 |
| 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 |
| CH853780A CH625808A5 (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 |
| CH683081A CH631998A5 (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 |
| CH4682A CH632521A5 (en) | 1976-09-29 | 1982-01-06 | Process for the preparation of polyhalogenated steroids |
Family Applications Before (4)
| 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 |
| 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 |
Family Applications After (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH683281A CH632000A5 (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 |
| CH683181A CH631999A5 (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) | DE2743069C2 (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 |
| AU7556291A (en) * | 1990-03-27 | 1991-10-21 | Schering Corporation | Process for 9alpha-hydroxy steroid dehydration |
| US5972922A (en) * | 1990-06-11 | 1999-10-26 | Alcon Laboratories, Inc. | Steroids which inhibit angiogenesis |
| BR0214520A (en) | 2001-11-29 | 2006-05-30 | Taro Pharmaceuticals Usa Inc | Method for the preparation of 6alphafluoro 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 |
| LT3310389T (en) | 2015-06-18 | 2020-11-10 | Bausch Health Ireland Limited | Topical compositions comprising a corticosteroid and a retinoid for treating psoriasis |
Family Cites Families (3)
| 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 |
-
1976
- 1976-09-29 LU LU75903A patent/LU75903A1/xx unknown
- 1976-12-09 CH CH1549976A patent/CH624967A5/en not_active IP Right Cessation
-
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 DE2743069A patent/DE2743069C2/en not_active Expired
- 1977-09-26 CH CH1172177A patent/CH632279A5/en not_active IP Right Cessation
- 1977-09-27 DD DD7700201226A patent/DD133150A5/en unknown
- 1977-09-27 CA CA287,560A patent/CA1101410A/en not_active Expired
- 1977-09-27 FR FR7729043A patent/FR2366311A1/en active Granted
- 1977-09-27 CY CY1178A patent/CY1178A/en unknown
- 1977-09-27 GB GB40131/77A patent/GB1563638A/en not_active Expired
- 1977-09-27 AU AU29148/77A patent/AU514200B2/en not_active Expired
- 1977-09-28 BE BE181243A patent/BE859120A/en not_active IP Right Cessation
- 1977-09-28 IL IL53012A patent/IL53012A/en unknown
- 1977-09-28 HU HU77CI1774A patent/HU175218B/en unknown
- 1977-09-28 ZA ZA00775800A patent/ZA775800B/en unknown
- 1977-09-28 AT AT0691077A patent/AT363197B/en not_active IP Right Cessation
- 1977-09-28 IE IE1979/77A patent/IE46047B1/en not_active IP Right Cessation
- 1977-09-29 ES ES462763A patent/ES462763A1/en not_active Expired
- 1977-09-29 JP JP11619377A patent/JPS5356652A/en active Granted
-
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
-
1980
- 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
- 1980-11-18 CH CH853780A patent/CH625808A5/en not_active IP Right Cessation
-
1981
- 1981-10-26 CH CH683281A patent/CH632000A5/en not_active IP Right Cessation
- 1981-10-26 CH CH683081A patent/CH631998A5/en not_active IP Right Cessation
- 1981-10-26 CH CH683181A patent/CH631999A5/en not_active IP Right Cessation
-
1982
- 1982-01-06 CH CH4682A patent/CH632521A5/en not_active IP Right Cessation
-
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
-
1984
- 1984-12-30 MY MY92/84A patent/MY8400092A/en unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE2655570A1 (en) | NEW POLYHALOGSTEROIDS AND METHODS FOR THEIR PRODUCTION | |
| DD227966A5 (en) | PROCESS FOR THE PRODUCTION OF NEW CARBONIC ACID ESTERS | |
| CH625808A5 (en) | Process for the preparation of polyhalogenated steroids | |
| CH615934A5 (en) | ||
| CH537917A (en) | Delta-16-steroids | |
| EP0003341B1 (en) | 11,17-substituted pregnanes, their preparation and application for the preparation of pharmaceutical compositions | |
| DE1181705B (en) | Process for the preparation of 16β-lower-alkylcortisones, -hydrocortisones, -prednisones and -prednisolones and of their 9 alpha-halogen derivatives and 21-esters | |
| DE3400188A1 (en) | NEW 6 (ALPHA), 16 (ALPHA) DIMETHYL CORTICOIDS | |
| CH655320A5 (en) | METHOD FOR PRODUCING CORTICOSTEROID ESTERS BY MEANS OF SELECTIVE SOLVOLYSIS. | |
| DE2365992A1 (en) | 6 ALPHA-FLUORO-17,21-DIHYDROXY-16 BETA-METHYLPREGNA-4,9 (11) -DIEN-3,20-Dione-17,21-DIACETATE AND METHOD FOR PRODUCING IT | |
| DE2448662C2 (en) | 6α-Fluoro-16α-methyl-1,4,8-pregnatriene-3,20-dione derivatives, processes for their preparation and pharmaceuticals containing them | |
| DE2756550C2 (en) | Process for the preparation of 3,20-dioxo-7α-halo-4-pregnenen and 1,4-pregnadienes, 3,20-dioxo-7α-chloro and bromo-1,4-pregnadienes and drugs containing the latter | |
| EP0077541A1 (en) | Delta-1,3,5-3-chloro-11 beta, 16 alpha, 17 alpha, 21-tetrahydroxy-pregnan-20-one-16,17-acetonide derivatives, process for their preparation and pharmaceutical preparations containing them | |
| DE1618917C3 (en) | 6 alpha, 21-difluorosteroids and processes for their production | |
| CH625254A5 (en) | ||
| CH631185A5 (en) | Multiply halogenated steroids | |
| CH621801A5 (en) | Process for the preparation of polyhalosteroids | |
| CH617709A5 (en) | ||
| DE1768673B1 (en) | 6alpha, 9alpha-difluorprednisolone-17,21-diester | |
| DE1175668B (en) | Process for the production of 9ª ‡, 11ª ‰ -dihalogen compounds of the pregnane or androstane series | |
| DE1443176A1 (en) | 6 alpha-fluoro-16-beta-methyl-4-pregnene and -1,4-pregnadienes and process for their preparation | |
| DE3143757A1 (en) | NEW CORTICOIDS, THEIR PRODUCTION AND USE | |
| DE1075606B (en) | Process for the production of halogenated 4,6 pregnadiene-3-keto steroids | |
| CH385206A (en) | Process for making steroid compounds | |
| DE2809732A1 (en) | 17-Acylated 9-fluoro-prednisolone derivs. - which are local antiinflammatories free of systemic effects and useful for treating e.g. eczema and asthma |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PL | Patent ceased |