DD210694A5 - PROCESS FOR THE PREPARATION OF 6ALPHA-METHYL PREDNISOLONE DERIVATIVES - Google Patents
PROCESS FOR THE PREPARATION OF 6ALPHA-METHYL PREDNISOLONE DERIVATIVES Download PDFInfo
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- DD210694A5 DD210694A5 DD83258236A DD25823683A DD210694A5 DD 210694 A5 DD210694 A5 DD 210694A5 DD 83258236 A DD83258236 A DD 83258236A DD 25823683 A DD25823683 A DD 25823683A DD 210694 A5 DD210694 A5 DD 210694A5
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07J21/00—Normal steroids containing carbon, hydrogen, halogen or oxygen having an oxygen-containing hetero ring spiro-condensed with the cyclopenta(a)hydrophenanthrene skeleton
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- 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]
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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
- C07J5/0053—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 not substituted in position 16
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Abstract
Description
" ' Berlin, den 6· 10. 1983 62 998 18Berlin, the 6th 10th 1983 62 998 18
Verfahren zur Herstellung \on oiX-Methylprednisolon-DerivatenProcess for the preparation of oiX-methylprednisolone derivatives
Die vorliegende Erfindung betrifft ein Verfahren zur Herstellung von βα,-Methylprednisolon-Derivaten der nachfolgend genannten allgemeinen Formel I.The present invention relates to a process for the preparation of βα, -methylprednisolone derivatives of the general formula I.
Der am nächsten liegende Stand der Technik ist in den DE-Patentanmeldungen Nr. 26 45 104, 26 45 105 und 23 40 591 und 19 58 549 sowie in der US-PS 33 83 394 oder in der. Publikation J. Amer. Soc, 79, 1957, 1515 beschrieben.The closest prior art is in DE Patent Application Nos. 26 45 104, 26 45 105 and 23 40 591 and 19 58 549 and in the US-PS 33 83 394 or in the. Publication J. Amer. Soc, 79, 1957, 1515.
Es wurde gefunden, daß die erfindungsgemäßen Derivate des ό<Χ'-Me thy !prednisolone überraschenderweise oft bei topischer Applikation eine signefikant stärkere Y/irksamkeit besitzen als die vorbekannten Derivate des 60^-Methylprednisolons· Diese Wirksamkeit ist oft sogar noch signifikant stärker als diejenige difluorierter "Edelkortikoide", wie etwa das 6 »χ, 9<x -Difluor-11 ß-hydroxy-16 ο-methyl-21 -valeryloxy-1,4-pregnadien-3,20-dion.Surprisingly, it has been found that the derivatives according to the invention of the ό <Χ'-methyl thy- prednisone often have a signifi- cantly stronger activity when applied topically than the previously known derivatives of the 60-methylprednisolone. This activity is often even significantly greater than that difluorinated "corticosteroids", such as the 6 »χ, 9 < -difluoro-11β-hydroxy-16α-methyl-21-valeryloxy-1,4-pregnadiene-3,20-dione.
Bei systemischer Applikation sind diese Derivate des Methylprednisolons überraschenderweise oft schwächer wirksam als die entsprechenden vorbekannten Derivate des 6cC-Methy!prednisolone.When administered systemically, these derivatives of methylprednisolone are surprisingly often less effective than the corresponding prior art derivatives of 6cC-methyl prednisolone.
62 998 1862 998 18
Der Erfindung liegt die Aufgabe zugrunde, neue 6cL-läethylprednisolon-Derivate zur Verfügung zu stellen·The invention has the object to provide novel 6 cL -läethylprednisolon derivatives available ·
Gegenstand der Erfindung ist ein Verfahren zur Herstellung von ooC-Methylprednisolon-Derivaten der allgemeinen Pormel IThe invention relates to a process for the preparation of ooC-methylprednisolone derivatives of the general Pormel I.
GH2OR2 GH 2 OR 2
HOHO
(D,(D,
CH-CH-
worin .. \ \ : / : //':' : ' -../^, ;. ;;-.;. ' . ' '' . R1 einen 1-Oxoalkylrest mit 2 bis ß Kohlenstoffatomen oder einen Benzoylrest undwhere .. \\ : /: // ':': ' - .. / ^,;. ;; -. ; , '. '''. R 1 is a 1-oxoalkyl radical having 2 to ß carbon atoms or a benzoyl radical and
R2 ein Wasserstoffatom, einen 1-Oxoalkylrest mit 2 bis 6 Kohlenstoffatomen oder einen Benzoylrest bedeuten, welches sich dadurch auszeichnet, daß man in an sich bekannter Weise aus einem Kortikoid der allgemeinen Formel IIIR 2 is a hydrogen atom, a 1-oxoalkyl radical having 2 to 6 carbon atoms or a benzoyl radical, which is characterized in that in a conventional manner from a corticoid of the general formula III
CH9OR0 =0CH 9 OR 0 = 0
"OR."OR.
(Ill),(Ill),
62 998 18 ' . - 3 -62 998 18 '. - 3 -
R. und Rp die obengenannte Bedeutung besitzen, Bromwasserstoff abspaltet·R. and Rp have the abovementioned meaning, splits off hydrogen bromide ·
Die neuen 6ty.~Methylprednisolon-Derivate können nach dem erfindungsgemäßen Verfahren hergestellt werden, welches unter den Bedingungen durchgeführt werden kann, wie sie in den deutschen Patentanmeldungen Ur. 26 45 104, 26 45 und 23 40 591 und 19 58 549 sowie im US-Patent Nr. 3 383 oder in der Publikation J. Amer. Chem. Soc.,72, Ί957, 1515 beschrieben sind.The new 6ty.-methylprednisolone derivatives can be prepared by the process according to the invention, which can be carried out under the conditions described in German Patent Applications Ur. 26 45 104, 26 45 and 23 40 591 and 19 58 549 and in US Pat. No. 3,383 or in the publication J. Amer. Chem. Soc., 72, Ί957, 1515.
Die neuen öcc-Methylprednisolon-Derivate der allgemeinen i'ormel I können als 2 bis 6 Kohlenstoffatome enthaltende 1-Oxoalkyigruppen R. und Rp beispielsweise eine Acetylgruppe, eine Propionylgruppe, eine Butyrylgruppe, eine Isobutyrylgruppe, eine Valerylgruppe, eine 3-Methylbutyrylgruppe, eine Irimethylacetylgruppe oder eine Hexanoylgruppe tragen.The new α-methylprednisolone derivatives of the general formula I can be 1- to 1-carbonyl-containing 1-oxoalkyl groups R. and Rp, for example, an acetyl group, a propionyl group, a butyryl group, an isobutyryl group, a valeryl group, a 3-methylbutyryl group, an irimethylacetyl group or carry a hexanoyl group.
Die neuen 6saC-Methylprednisolon-Derivate der allgemeinen Formel I eignen sich demzufolge in Kombination mit den in der galenischen Pharmazie üblichen Trägermitteln zur lokalen Behandlung von Kontaktdermatitis, Ekzemen der verschiedensten Art, lieurodermatosen, Erythrodermie, Verbrennungen, Pruritis vulvae et ani, Rosacea, Erythematodes cutaneus, Psorasis, Liehen ruber planus et verrueosus und ähnlichen Hauterkrankungen·The new 6saC-methylprednisolone derivatives of the general formula I are accordingly suitable in combination with the carriers customary in galenic pharmacy for the local treatment of contact dermatitis, eczema of the most diverse types, lieurodermatoses, erythroderma, burns, pruritis vulvae et ani, rosacea, cutaneous erythematosus , Psorasis, lichen planus and verruosus and similar skin diseases ·
Me Herstellung der Arzneimittelspezialitäten erfolgt in üblicher Weise, indem man die Wirkstoffe mit geeigneten Zusätzen in die gewünschte Applikationsform, wie zum Beispiel: Lösungen, Lothionen, Salben, Cremen oder Pflaster, überführt. In den so formulierten Arzneimitteln ist dieMe preparation of the drug specialties in a conventional manner, by converting the active ingredients with suitable additives in the desired application form, such as: solutions, lotions, ointments, creams or patches. In the drugs formulated in this way, the
62 998 18 -4-62 998 18 -4-
Wirkstoffkonzentration von der Applikationsform abhängig· Bei Lotionen und Salben wird vorzugsweise eine Wirkstoffkonzentration von 0,001 ίο bis 1 % verwendet.Active substance concentration depends on the application form · For lotions and ointments an active substance concentration of 0.001 to 1 % is preferably used.
Darüber hinaus sind die neuen Verbindungen gegebenenfalls in Kombination mit den üblichen Trägermitteln und Hilfsstofi'en auch gut zur Herstellung von Inhalationsmitteln geeignet, welche zur Therapie allergischer Erkrankungen der Atomwege wie zum Beispiel des Bronchialasthmas oder der Rhinitis verwendet werden können.In addition, the novel compounds, optionally in combination with the usual carriers and excipients, are also well-suited for the preparation of inhalants which can be used to treat allergic diseases of the nuclear pathways such as bronchial asthma or rhinitis.
Ferner eignen 3ich die neuen Kortikoide auch in Form von Kapseln, Tabletten oder Dragees, die vorzugsweise 10 bis 200 mg Wirkstoff enthalten und oral appliziert werden oder in Form von Suspensionen, die vorzugsweise 100 bis 500 mg Wirkstoff pro Dosiseinheit enthalten und rektal appliziert werden. Auch zur Behandlung allergischer Erkrankungen des Darmtraktes, wie der Kolitis ulcerosa und der Kolitis granulomatosa.Furthermore, the new corticosteroids are also suitable in the form of capsules, tablets or dragees which preferably contain 10 to 200 mg of active ingredient and are administered orally or in the form of suspensions which preferably contain 100 to 500 mg of active ingredient per dose unit and are rectally applied. Also for the treatment of allergic diseases of the intestinal tract, such as ulcerative colitis and granulomatous colitis.
Die nachfolgenden Ausführungsbeispiele dienen zur Erläuterung de3 erfindungsgemäßen Verfahrens.The following exemplary embodiments serve to explain the method according to the invention.
Ausführungsbeispiele Beispiel 1Exemplary embodiments Example 1
A) Eine Suspension von 34,0 g 21-Acetoxy-9%-brom-1iß,i7-dihydroxy-6^-methyl-1,4-pregnadien-3»20-dion in 1,36 Methanol und 120 ml 70%iger Perchlorsäure wird 20 h bei Raumtemperatur gerührt. Nach der Eiswasserfällung wird der niederschlag abgesaugt, mit Wasser neutralgewaschen und im Vakuumtrockenschrank getrocknet. Man erhält 28,3 g 9t*/-Brom-11ß, 17»21~trihydroxy-6üü-methyl-i,4-pregnadien-3,20-dion. Schmp. 159-160 0C.A) A suspension of 34.0 g of 21-acetoxy-9% bromo-1β, i7-dihydroxy-6α-methyl-1,4-pregnadiene-3,20-dione in 1,36 methanol and 120 ml 70%. iger perchloric acid is stirred for 20 h at room temperature. After the ice water precipitation, the precipitate is filtered off, washed neutral with water and dried in a vacuum oven. This gives 28.3 g of 9t * / - bromo-11ß, 17 »21 ~ trihydroxy-6üü-methyl-i, 4-pregnadiene-3,20-dione. M.p. 159-160 0 C.
62 998 18 - 5 -62 998 18 - 5 -
B) Aus einer Lösung von 4,3 g 9t\/-Brom-11ß,17,21-trihydroxy-6 λ-methyl-1,4-pregnadien-3,20-dion und 430mg Pyridiniumtosylat in 34,5 ml Dimethylformamid und 300 ml Benzol werden bei 130 0C über einen Wasserabscheider 129 ml Benzol abdestilliert. In die heiße Reaktionslösung läßt man 10,3 ml Orthobuttersäuretrimethylester hinzutropfen und destilliert anschließend weiter Benzol und andere leichtflüchtige Reaktionskomponenten ab. Man fügt 5 ml Pyridin hinzu und engt i· Vak. zur Trockne ein· Es wird 9 oi-Brom-11 ß-hydroxy-17 <X, 21 - (1-methoxybutylidendioxy)-6x-methyl-l,4-pregnadien-3,20-dion als 01 isoliert.B) From a solution of 4.3 g of 9t / bromo-11β, 17,21-trihydroxy-6λ-methyl-1,4-pregnadiene-3,20-dione and 430 mg of pyridinium tosylate in 34.5 ml of dimethylformamide and 300 ml of benzene are distilled off at 130 0 C via a water separator 129 ml of benzene. 10.3 ml of trimethyl orthobutyrate are added dropwise to the hot reaction solution and benzol and other readily volatile reaction components are subsequently distilled off. Add 5 ml of pyridine and concentrate in vacuo. It is isolated to dryness 9 o -bromo-11β-hydroxy-17 <X, 21 - (1-methoxybutylidendioxy) -6x-methyl-l, 4-pregnadiene-3,20-dione.
C) Das rohe 9<jC-Brom~i Iß-hydroxy-i7o^.21-(i-methoxybutyliden-dioxy)-6^-methyl-1,4-pregnadien-3,20~dion wird in 129 ml Methanol gelöst und mit einem Gemisch aus 46,4 ml 0,1H wäßriger Essigsäure und 5,2 ml O,1M wäßriger Natriumacetatlösung 1 h bei 00 0C Badtemperatur gerührt. Man engt die Lösung auf v/3 ihres Volumens ein, gibt auf Wasser und wäscht die Bssigesterextrakte neutral. iJach dem Irocknen und Einengen wird das Rohprodukt an 200 g Kieselgel mit einem Hexan-Aceton-Gradienten (0-60 % Aceton) gereinigt. Man isoliert 3,7 g 9<£-Brom-17<a/-butyryloxy-11ß,21-dihydroxy-6 &-methyl-1,4-pregnadi en-3,20-dion. Schmp. 158-159 0CC) The crude 9 <jC-bromo-1β-hydroxy-i7o ^ .21- (i-methoxybutylidene-dioxy) -6 ^ -methyl-1,4-pregnadiene-3,20 ~ dione is dissolved in 129 ml of methanol and stirred with a mixture of 46.4 ml of 0.1H aqueous acetic acid and 5.2 ml of O, 1M aqueous sodium acetate solution for 1 h at 00 0 C bath temperature. The solution is concentrated to v / 3 of its volume, added to water and washed the Bssigesterextrakte neutral. After drying and concentration, the crude product is purified on 200 g of silica gel with a hexane-acetone gradient (0-60 % acetone). 3.7 g of 9 £ -bromo-17 <a / -butyryloxy-11β, 21-dihydroxy-6 & -methyl-1,4-pregnadiene-3,20-dione are isolated. M. 158-159 0 C
D) Eine Suspension von 3,0 g 9o£~Brom-i7iX"-butyryloxy-11ß,21-dihydroxy-6cx -methyl-1,4-pregnadien-3,20-dion in 60 ml Hexamethylphosphorsäuretriamid wird mit 3,0 g Lithiumchlorid 1 h bei 80 0C Badtemperatur gerührt. JMach der Eiswasserfällung wird der Rückstand abfiltriert, mit Wasser gewaschen und das Rohprodukt an 105 g Kieselgel mit e'inem Methylenchlorid-Aceton-Gradienten (0-20 % Aceton) gereinigt. Man isoliert 938 ml 17^-Butyryloxy-D) A suspension of 3.0 g £ 9o ~ bromo-i7 iX "-butyryloxy-11beta, 21-dihydroxy-6cx -methyl-1,4-pregnadien-3,20-dione in 60 ml of hexamethylphosphoric triamide with 3.0 g of lithium chloride for 1 h at 80 0 C. bath temperature. JMach of ice water precipitation, the residue is filtered off, washed with water and the crude product chromatographed on 105 g silica gel with e'inem methylene chloride-acetone gradient (0-20% acetone). One isolated 938 ml of 17-butyrolactone
62 998 18 - 6 -62 998 18 - 6 -
-11 ß, 21-dihydroxy-6 oc-methyl-1,4,8-pregnatsiien-3,20-dion als Schaum. ££v/q = -53,8 (Chloroform)·-11β, 21-dihydroxy-6 oc-methyl-1,4,8-pregnatsien-3,20-dione as a foam. ££ v / q = -53.8 (chloroform) ·
A) Analog Beispiel 1B) werden 17,4 g 9<36-Brom-i1ß, 17<* j 21-trihydroxy-6-x-methyl-1,4-pre»gnadien-3,20-dion mit 42,0 ml Ortliobenzoesäuretriethylester umgesetzt und aufgearbeitet· Man isoliert 9^-BrOm-17^ , 21-(1-ethoxyben2;ylidendioxy)-1 1ß-hydroxy-6ος-methyl-1,4-pregnadien-3,20-dion als ül.A) Analogously to Example 1B) are 17.4 g of 9 <36-bromo-i1ß, 17 <* 21-trihydroxy-6-x-methyl-1,4-pragnadiene-3,20-dione with 42.0 triethyl ester of aminovinylbenzoate is reacted and worked up. 9-Bromo-17-, 21- (1-ethoxybenzylidene-dioxy) -1,1β-hydroxy-6α-methyl-1,4-pregnadiene-3,20-dione are isolated as an aliquot.
B) Das rohe 9c^-Brom-17^,21-(i-ethoxybenzylidendioxy)~11ßhydroxy-6;3C-methyl-1,4-pregnadien-3,20-dion wird unter den Bedingungen des Beispiels 1C) hydrolysiert und aufgearbeitet. Das Rohprodukt wird an 1 kg Kieselgel mit einem Hexan-Acetön-Gradienten (0.50 & Aceton) gereinigt. Ausbeute 12,47 g 17oi.-Benzoyloxy-9^C-brom-11 ß,21 -dihydroxy- 6c£ -methyl-Λ ,4-pregnadien-3,20-dion· Schmp. 159 0C.B) The crude 9c-bromo-17 ^, 21- (i-ethoxybenzylidenedioxy) ~ 11β-hydroxy-6; 3C-methyl-1,4-pregnadiene-3,20-dione is hydrolyzed and worked up under the conditions of Example 1C) , The crude product is purified on 1 kg silica gel with a hexane-acetone gradient (0.50 & acetone). Yield 12.47 g 17oi.-benzoyloxy-9 ^ C-bromo-11 beta, 21-dihydroxy 6c £ Λ methyl-, 4-pregnadiene-3,20-dione mp. 159 0 C.
C) Eine Lösung von 2,0 g 17«^ -Benzoyloxy-9oc-brom-11ß,21 dihydroxy-6oo-methyl-1,4-pregnadien-3,20-dion wird mit 2,0 g Lithiumchlorid analog Beispiel 1D) umgesetzt und aufgearbeitet. Das Rohprodukt wird an 105 g Kieselgel mit einem MethylenChlorid Aceton-Gradienten (0-20 % Aceton) gereinigt· Ausbeute .1,2 g 17^-Benzoyloxy-Hß,21· dihydroxy-6 t*-me thyl-1 ^,S-pregnatyien^, 20-dion· Schmp. 206 - 208 0C,C) A solution of 2.0 g of 17'-benzoyloxy-9oc-bromo-11β, 21-dihydroxy-6oo-methyl-1,4-pregnadiene-3,20-dione is mixed with 2.0 g of lithium chloride analogously to Example 1D). implemented and worked up. The crude product is purified on 105 g of silica gel with a methylene chloride acetone gradient (0-20 % acetone). Yield. 1.2 g of 17-benzoyloxy-H 2 O, 21-dihydroxy-6-t-methyl-1, S -pregnatyls, 20-dione · m.p. 206-208 0 C,
A) 3,0 g 17v/i/-Benzoyloxy-9.«c-brom-11 ß,21 -dihydroxy-6<&- methyl-1,4-pregnadien-3,20-dion werden in 30 ml PyridinA) 3.0 g of 17v / i / benzoyloxy-9. "C-bromo-11β, 21 -dihydroxy-6 <& -methyl-1,4-pregnadiene-3,20-dione are dissolved in 30 ml of pyridine
62 998 1862 998 18
mit 15 ml Acetanhydrid 3 h bei Raumtemperatur gerührt. Wach der üblichen Aufarbeitung erhält man 3»2 g 21-Acetoxy-i7v£-benzoyloxy~9ov-brom-11ß-hydroxy-6Qt methyl-1,4-pregnadien-3,20-dion· ochmp. 172 - 173 0G.stirred with 15 ml of acetic anhydride for 3 h at room temperature. Wake up the usual work-up to obtain 3 »2 g of 21-acetoxy-7a-benzoyloxy ~ 9 ov -bromo-11β-hydroxy-6Q t -methyl-1,4-pregnadiene-3,20-dion.mpmp. 172 - 173 0 G.
B) 3,3 g 21-Acetoxy-17o£-benzoyloxy~9^-brom-11ßhydroxy-6^ty-methyl-1,4-pregnadien-3,20-dion werden analog Beispiel 1D) mit 3»3 g Lithiumchlorid umgesetzt und aufgearbeitet· Das Rohprodukt wird an 200 g Kieselgel mit einem Methylenchlorid-Aceton-Gradienten (0 - 15 % Aceton) gereinigt. Ausbeute 1,78 g 21-Acetoxy-17 A/-benzoyloxy-11ß-hydroxy-6 oC-methyl-1, 4,8-pregnatrien-3,20-dion. Schmp. 229 - 230 0C.B) 3.3 g of 21-acetoxy-17o-benzoyloxy-9-bromo-11β-hydroxy-6-yl-methyl-1,4-pregnadiene-3,20-dione are analogous to Example 1D) with 3 g of lithium chloride reacted and worked up. The crude product is purified on 200 g of silica gel with a methylene chloride-acetone gradient (0-15 % acetone). Yield 1.78 g of 21-acetoxy-17A / -benzoyloxy-11β-hydroxy-6 oC-methyl-1,4,8-pregnatriene-3,20-dione. Mp 229 -. 230 0 C.
A) Analog Beispiel 3A) werden 3,0 g 17 <sC--Benzoyloxy-9oobrom-11ß,21-dihydroxy-6 °* -methyl-1,4-pregnadien-3,20-dion mit Propionsäureanhydrid umgesetzt und aufgearbeitet. Man erhält 3,1 g 17·> -Benzoyloxy^^-brom-Hßhydroxy-6 o*- -methyl-21 -propionyloxy-1,4-pregnadien-3,20-dion. Schmp. 155 - 15b 0G.A) Analogously to Example 3A) 3.0 g of 17 <sC - benzoyloxy-9oobrom-11ß, 21-dihydroxy-6 ° * -methyl-1,4-pregnadiene-3,20-dione reacted with propionic anhydride and worked up. This gives 3.1 g of 17 ·> -Benzoyloxy ^^ - bromo-Hßhydroxy-6 o * - methyl-21-propionyloxy-1,4-pregnadiene-3,20-dione. M.p. 155 - 15b 0 G.
B) 3,2 g i7c*>-Benzoyloxy-9^-brom-11ß~hydroxy-6oomethyl-21-propionyloxy 1,4-pregnadien-3,20-dion werden unter den Bedingungen des Beispiels 1D) mit Lithiumchiorid umgesetzt, aufgearbeitet und gepeinigt. Man iso-Iiert 1,96 g 17 ^ -Benzoyloxy-1 Tß-hydroxy-6 vjc -methyl-21-propionyloxy-1,4,8-pregnatrien-3,20-dion. Schmp. 225 - 226 0C.B) 3.2 g of i7c *> - benzoyloxy-9 ^ -bromo-11β-hydroxy-6o-ethyl-21-propionyloxy-1,4-pregnadiene-3,20-dione are reacted under the conditions of Example 1D) with lithium chloride, worked up and tormented. Iso-Iiert 1.96 g of 17 ^ -Benzoyloxy-1 Tβ-hydroxy-6 vjc-methyl-21-propionyloxy-1,4,8-pregnatriene-3,20-dione. Mp 225 -. 226 0 C.
Claims (5)
aus einem Kortikoid der allgemeinen i'ormel IIIHp is a hydrogen atom, a 1-oxoalkyl radical having 2 to 6 carbon atoms or a benzoyl radical, characterized in that in a manner known per se
from a corticosteroid of the general i'ormel III
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19823248435 DE3248435A1 (en) | 1982-12-23 | 1982-12-23 | NEW 6 (ALPHA) METHYLPREDNISOLONE DERIVATIVES THEIR PRODUCTION AND USE |
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| Publication Number | Publication Date |
|---|---|
| DD210694A5 true DD210694A5 (en) | 1984-06-20 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DD83258236A DD210694A5 (en) | 1982-12-23 | 1983-12-20 | PROCESS FOR THE PREPARATION OF 6ALPHA-METHYL PREDNISOLONE DERIVATIVES |
Country Status (21)
| Country | Link |
|---|---|
| EP (1) | EP0112467B1 (en) |
| JP (1) | JPS59130300A (en) |
| AT (1) | ATE28878T1 (en) |
| AU (1) | AU2220283A (en) |
| CA (1) | CA1250571A (en) |
| CS (1) | CS236900B2 (en) |
| DD (1) | DD210694A5 (en) |
| DE (2) | DE3248435A1 (en) |
| DK (1) | DK159118C (en) |
| ES (1) | ES528323A0 (en) |
| GB (1) | GB2132620B (en) |
| GR (1) | GR79453B (en) |
| HU (1) | HU187939B (en) |
| IE (1) | IE56400B1 (en) |
| IL (1) | IL70452A (en) |
| NO (1) | NO156410C (en) |
| PL (1) | PL141513B1 (en) |
| PT (1) | PT77880B (en) |
| RO (1) | RO88666A (en) |
| SU (1) | SU1299514A3 (en) |
| ZA (1) | ZA839573B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6141820A (en) * | 1996-10-28 | 2000-11-07 | Firma Carl Freudenberg | Floor-cloth-type covering |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1026160A (en) * | 1964-04-29 | 1966-04-14 | American Cyanamid Co | Pregnatrienes |
| DE2645104C2 (en) * | 1976-10-04 | 1986-04-24 | Schering AG, 1000 Berlin und 4709 Bergkamen | 11β-Hydroxy-1,4,8-pregnatriene-3,20-dione derivatives and processes for their preparation |
-
1982
- 1982-12-23 DE DE19823248435 patent/DE3248435A1/en not_active Withdrawn
-
1983
- 1983-11-03 EP EP83110948A patent/EP0112467B1/en not_active Expired
- 1983-11-03 AT AT83110948T patent/ATE28878T1/en active
- 1983-11-03 DE DE8383110948T patent/DE3372970D1/en not_active Expired
- 1983-11-16 CA CA000441287A patent/CA1250571A/en not_active Expired
- 1983-12-08 AU AU22202/83A patent/AU2220283A/en not_active Abandoned
- 1983-12-14 IE IE2944/83A patent/IE56400B1/en not_active IP Right Cessation
- 1983-12-15 IL IL70452A patent/IL70452A/en not_active IP Right Cessation
- 1983-12-16 SU SU833673977A patent/SU1299514A3/en active
- 1983-12-19 GB GB08333741A patent/GB2132620B/en not_active Expired
- 1983-12-20 DD DD83258236A patent/DD210694A5/en unknown
- 1983-12-20 RO RO83112962A patent/RO88666A/en unknown
- 1983-12-21 PL PL1983245246A patent/PL141513B1/en unknown
- 1983-12-21 GR GR73318A patent/GR79453B/el unknown
- 1983-12-21 HU HU834382A patent/HU187939B/en not_active IP Right Cessation
- 1983-12-22 NO NO834759A patent/NO156410C/en unknown
- 1983-12-22 ES ES528323A patent/ES528323A0/en active Granted
- 1983-12-22 PT PT77880A patent/PT77880B/en unknown
- 1983-12-22 ZA ZA839573A patent/ZA839573B/en unknown
- 1983-12-23 JP JP58242345A patent/JPS59130300A/en active Granted
- 1983-12-23 DK DK597783A patent/DK159118C/en not_active IP Right Cessation
- 1983-12-23 CS CS839879A patent/CS236900B2/en unknown
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6141820A (en) * | 1996-10-28 | 2000-11-07 | Firma Carl Freudenberg | Floor-cloth-type covering |
Also Published As
| Publication number | Publication date |
|---|---|
| PL245246A1 (en) | 1984-10-22 |
| EP0112467B1 (en) | 1987-08-12 |
| PL141513B1 (en) | 1987-08-31 |
| JPS59130300A (en) | 1984-07-26 |
| CA1250571A (en) | 1989-02-28 |
| DE3372970D1 (en) | 1987-09-17 |
| RO88666A (en) | 1986-02-28 |
| JPH0415800B2 (en) | 1992-03-19 |
| ES8502128A1 (en) | 1985-01-01 |
| PT77880A (en) | 1984-01-01 |
| ZA839573B (en) | 1984-08-29 |
| PT77880B (en) | 1986-04-09 |
| NO156410C (en) | 1987-09-30 |
| GR79453B (en) | 1984-10-30 |
| IL70452A (en) | 1987-12-31 |
| CS236900B2 (en) | 1985-05-15 |
| HU187939B (en) | 1986-03-28 |
| IL70452A0 (en) | 1984-03-30 |
| NO156410B (en) | 1987-06-09 |
| AU2220283A (en) | 1984-06-28 |
| SU1299514A3 (en) | 1987-03-23 |
| GB2132620A (en) | 1984-07-11 |
| GB8333741D0 (en) | 1984-01-25 |
| ATE28878T1 (en) | 1987-08-15 |
| DK159118C (en) | 1991-02-11 |
| DK159118B (en) | 1990-09-03 |
| DK597783D0 (en) | 1983-12-23 |
| EP0112467A1 (en) | 1984-07-04 |
| IE832944L (en) | 1984-06-23 |
| DE3248435A1 (en) | 1984-06-28 |
| IE56400B1 (en) | 1991-07-17 |
| ES528323A0 (en) | 1985-01-01 |
| DK597783A (en) | 1984-06-24 |
| GB2132620B (en) | 1986-06-04 |
| NO834759L (en) | 1984-06-25 |
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