EP0000471A1 - New corticoids, process for their preparation and pharmaceutical compositions containing them - Google Patents

New corticoids, process for their preparation and pharmaceutical compositions containing them Download PDF

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Publication number
EP0000471A1
EP0000471A1 EP78100135A EP78100135A EP0000471A1 EP 0000471 A1 EP0000471 A1 EP 0000471A1 EP 78100135 A EP78100135 A EP 78100135A EP 78100135 A EP78100135 A EP 78100135A EP 0000471 A1 EP0000471 A1 EP 0000471A1
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Prior art keywords
group
corticoids
general formula
dihydroxy
oxo
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German (de)
French (fr)
Inventor
Henry Dr. Laurent
Rudolf Prof. Wiechert
Hans Dr Wendt
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Bayer Pharma AG
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Schering AG
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J71/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
    • C07J71/0036—Nitrogen-containing hetero ring
    • C07J71/0042—Nitrogen only
    • C07J71/0047—Nitrogen only at position 2(3)

Definitions

  • the invention relates to new corticoids, a process for their preparation and pharmaceutical preparations which contain these corticoids as an active ingredient.
  • New corticoids processes for their preparation and pharmaceutical preparations containing them.
  • alkanoyloxy group Y should preferably be understood to mean a group which is derived from a saturated aliphatic monocarboxylic acid containing 1 to 8 carbon atoms.
  • alkanoyloxy groups include:
  • the acetoxy group, the propionyloxy group, the butyryloxy group, the pentanoyloxy group and the hexanoyioxy group are acetoxy groups, the propionyloxy group, the butyryloxy group, the pentanoyloxy group and the hexanoyioxy group.
  • An alkoxy group Y is preferably understood to mean an alkoxy group containing 1 to 6 carbon atoms, such as, for example, the methoxy group, ethoxy group, propyloxy group or butyloxy group.
  • the process according to the invention for the preparation of the new corticosteroid is characterized in that the methylenedioxy groups of a compound of the general formula II hydrolytically cleaves,
  • the 21-hydroxy group esterified or to the aldehyde group is oxidized and the aldehyde obtained is oxidized in the presence of an alcohol with atmospheric oxygen or manganese (IV) oxide.
  • the cleavage of the methylenedioxy groups and the acylation of the 21-hydroxysteroid formed can be carried out, for example, under the conditions described in German Patent 1,072,622.
  • the reaction conditions are suitable, as described in German Offenlegungsschrift 24 41-284.
  • the new corticoids of the general formula I are pharmacologically active substances which are distinguished in particular by the fact that, when applied topically, they have a pronounced anti-inflammatory activity, while they are systemically poorly effective or ineffective.
  • these compounds are often distinguished by a rapid onset of action, a high intensity and a long duration of action, they are inexpensive to absorb and, in galenical formulations, have relatively good stability.
  • the new compounds are suitable in combination with the excipients common in Galician pharmacy for the local treatment of contact dermatitis, various types of eczema, neurodermatoses, erythroderma, burns, pruritis vulvae et ani, rosacea erythematosus cutaneus, psoriasis, lichen planus et verrucosus and the like Skin diseases
  • the pharmaceutical specialties are produced in the usual way. Way, by converting the active ingredients with suitable additives in the desired application form, such as: solutions, lotions, ointments, creams or plasters.
  • suitable additives such as: solutions, lotions, ointments, creams or plasters.
  • the active substance concentration depends on the form of administration.
  • an active ingredient concentration of 0.01% to 1% is preferably avoided.
  • the new compounds if appropriate in combination with the customary carriers and auxiliaries, are also well suited for the production of inhalants.
  • the residue consists of 1.8 g of 2 '- (4-fluoro-phenyl) -11ß, 17 ⁇ -dihydroxy-20-oxo-2H'-2,4-pregnadieno [3,2-c] pyrazol-21-al.
  • Ma receives 251 mg of 2 '- (4-fluoro-phenyl) -11ß, 17 ⁇ -dihydroxy-20-oxo-2H'-2,4-pregnadieno [3,2-c] pyrazole-21-acidic acid methyl ester. Melting point 192 ° C (recrystallized from acetone-hexane).

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Steroid Compounds (AREA)

Abstract

Corticoids of the general formula I <IMAGE> in which X is two hydrogen atoms and Y is a hydroxyl or alkanoyloxy group or X is an oxygen atom and Y is a hydrogen atom, a hydroxyl group or an alkoxy group, are pharmacologically active substances which are particularly suitable for the treatment of inflammatory disorders and are prepared by hydrolysis of <IMAGE>

Description

Die Erfindung betrifft neue Kortikoide, ein Verfahren zu ihrer Herstellung und pharmazeutische Präparate, die diese Kortikoide als Wirkstoff enthalten.The invention relates to new corticoids, a process for their preparation and pharmaceutical preparations which contain these corticoids as an active ingredient.

Die neuen Kortikoide sind gekennzeichnet durch die allgemeine Formel I

Figure imgb0001
worin

  • X zwei Wasserstoffatome und Y eine Hydroxy- oder Alkanoyloxygruppe oder
  • X ein Sauerstoffatom und Y ein Wasserstoffatom, eine Hydroxygruppe oder eine Alkoxygruppe bedeuten.
The new corticoids are characterized by the general formula I.
Figure imgb0001
 wherein
  • X two hydrogen atoms and Y a hydroxy or alkanoyloxy group or
  • X represents an oxygen atom and Y represents a hydrogen atom, a hydroxyl group or an alkoxy group.

Neue Kortikoide, Verfahren zu ihrer Herstellung und diese enthaltende pharmazeutische Präparate.New corticoids, processes for their preparation and pharmaceutical preparations containing them.

Unter einer Alkanoyloxygruppe Y soll vorzugsweise eine Gruppe verstanden werden, die sich von einer 1 bis 8 Kohlenstoffatome enthaltenden gesättigten aliphatischen Monocarbonsäure ableitet. Als Alkanoyloxygruppen seien beispielsweise genannt:.An alkanoyloxy group Y should preferably be understood to mean a group which is derived from a saturated aliphatic monocarboxylic acid containing 1 to 8 carbon atoms. Examples of alkanoyloxy groups include:

Die Acetoxygruppe, die Propionyloxygruppe, die Butyryloxygruppe, die Pentanoyloxygruppe und die Hexanoyioxygruppe.The acetoxy group, the propionyloxy group, the butyryloxy group, the pentanoyloxy group and the hexanoyioxy group.

Unter einer Alkoxygruppe Y soll vorzugsweise eine 1 bis 6 Kohlen stoffatome enthaltende Alkoxygruppe, wie zum Beispiel die Methoxygruppe, Äthoxygruppe, Propyloxygruppe oder Butyloxygrupp verstanden werden.An alkoxy group Y is preferably understood to mean an alkoxy group containing 1 to 6 carbon atoms, such as, for example, the methoxy group, ethoxy group, propyloxy group or butyloxy group.

Das erfindungsgemäße Verfahren zur Herstellung der neuen Kortik: ist dadurch gekennzeichnet, daß man in an sich bekannter Weise die Methylendioxygruppen einer Verbindung der allgeneinen Formel II

Figure imgb0002
hydrolytisch abspaltet,The process according to the invention for the preparation of the new corticosteroid is characterized in that the methylenedioxy groups of a compound of the general formula II
Figure imgb0002
 hydrolytically cleaves,

gegebenenfalls die 21-Hydroxygruppe verestert oder zur Aldehydgruppe oxydiert und den erhaltenen Aldehyd in Gegenwart eines Alkohols mit Luftsauerstoff oder Mangan(IV)-oxyd oxydiert.optionally the 21-hydroxy group esterified or to the aldehyde group is oxidized and the aldehyde obtained is oxidized in the presence of an alcohol with atmospheric oxygen or manganese (IV) oxide.

Die Abspaltung der Methylendioxygruppen und die Acylierung des entstandenen 21-Hydroxysteroids kann beispielsweise unter den Bedingungen durchgeführt werden, wie sie in der deutschen Patentschrift 1 072 622 beschrieben sind. Zur Überführung des 21-Hydroxysteroids in den 21-Aldehyd und die 21-Säureester sind beispielsweise die Reaktionsbedingungen geeignet, wie sie in der deutschen Offenlegungsschrift 24 41-284 beschrieben sind.The cleavage of the methylenedioxy groups and the acylation of the 21-hydroxysteroid formed can be carried out, for example, under the conditions described in German Patent 1,072,622. For the conversion of the 21-hydroxysteroids into the 21-aldehyde and the 21-acid esters, for example, the reaction conditions are suitable, as described in German Offenlegungsschrift 24 41-284.

Die neuen Kortikoide der allgemeinen Formel I sind pharmakologisch wirksame Substanzen, die sich insbesondere dadurch auszeichnen, daß sie bei topischer Anwendung eine ausgeprägte antiinflammatorische Wirksamkeit besitzen, während sie systemisch gering wirksam oder unwirksam sind. Darüberhinaus zeichnen sich diese Verbindungen oft durch einen raschen Wirkungsbeginn, eine hohe Wirkungsintensität und eine lange Wirkungsdauer aus, sie haben eine günstige Resorbierbarkeit und in galenischen Zube- reitungen eine relativ gute Stabilität.The new corticoids of the general formula I are pharmacologically active substances which are distinguished in particular by the fact that, when applied topically, they have a pronounced anti-inflammatory activity, while they are systemically poorly effective or ineffective. In addition, these compounds are often distinguished by a rapid onset of action, a high intensity and a long duration of action, they are inexpensive to absorb and, in galenical formulations, have relatively good stability.

Die neuen Verbindungen eignen sich in Kombination mit den in der galehischen Pharmazie üblichen Trägermitteln zur lokalen Behandlung von Kontaktdermatitis, Ekzemen der verschiedensten Art, Neurodermatosen, Erythrodermie, Verbrennungen, Pruritis vulvae et ani, Rosacea Erythematodes cutaneus, Psoriasis, Lichen ruber planus et verrucosus und ähnlichen HauterkrankungenThe new compounds are suitable in combination with the excipients common in Galician pharmacy for the local treatment of contact dermatitis, various types of eczema, neurodermatoses, erythroderma, burns, pruritis vulvae et ani, rosacea erythematosus cutaneus, psoriasis, lichen planus et verrucosus and the like Skin diseases

Die Herstellung der Arzneimittelspezialitäten erfolgt in üblicher. Weise, indem man die Wirkstoffe mit geeigneten Zusätzen in die gewünschte Applikationsform, wie zum Beispiel: Lösungen, Lotionen, Salben, Cremen oder Pflaster, überführt. In den so formulierten Arzneimitteln ist die Wirkstoffkonzentration von der Applikationsform abhängig. Bei Lotionen und Salben wird vorzugsweise eine Wirkstoffkonzentration von O,01% bis 1% vermendet .The pharmaceutical specialties are produced in the usual way. Way, by converting the active ingredients with suitable additives in the desired application form, such as: solutions, lotions, ointments, creams or plasters. In the pharmaceuticals formulated in this way, the active substance concentration depends on the form of administration. In the case of lotions and ointments, an active ingredient concentration of 0.01% to 1% is preferably avoided.

Darüberhinaus sind die neuen Verbindungen gegebenenfalls in Kombination mit den üblichen Trägermitteln und Hilfsstoffe auch gut zur Herstellung von Inhalationsmitteln geeignet.In addition, the new compounds, if appropriate in combination with the customary carriers and auxiliaries, are also well suited for the production of inhalants.

Die nachfolgenden Beispiele dienen zur Erläuterung der Erfindung.The following examples serve to explain the invention.

Beispiel 1example 1

  • a) Eine Lösung von 5, 0 g llß-Hydroxy-2-hydroxymethylenthylen-17α,20;20-21-bismethylendioxy-4-pregnen-3-on in 50 ml konzentrierter Essigsäure wird mit 1,0 g Natriumacetat und 2,4 g 4-Fluor- phenylhydrazin-hydrochlorid versetzt und 5 Stunden bei Rauntemperatur gerührt. Das Reaktionsgemisch wird verdünnt und mit Dichlormethan extrahiert. Die organische Phase wird neutralgewaschen, getrocknet und im Vakuum eingeengt. Der Rückstand wird an Kieselgel chromatographiert. Mit Pentan-Äther (1:4) erhält man 1,80 g 2'-(4-Fluorphenyl)-17α,20; 20,21-bis- methylendioscy-2H'-2,4-pregnadieno[3,2-c]pyrazol-llß-ol vom Schmelzpunkt 176° C.a) A solution of 5.0 g llß-hydroxy-2-hydroxymethylene-17α, 20; 20-21-bismethylene-dioxy-4-pregnen-3-one in 50 ml of concentrated acetic acid is mixed with 1.0 g of sodium acetate and 2.4 g of 4-fluorophenylhydrazine hydrochloride are added and the mixture is stirred at room temperature for 5 hours. The reaction mixture is diluted and extracted with dichloromethane. The organic phase is washed neutral, dried and concentrated in vacuo. The residue is chromatographed on silica gel. With pentane ether (1: 4), 1.80 g of 2 '- (4-fluorophenyl) -17α, 20; 20,21-bis-methylenedioscy-2H'-2,4-pregnadieno [3,2-c] pyrazole-11ß-ol with a melting point of 176 ° C.
  • b) 3,5 g des vorstehend erhaltenen Produkts werden 3 Minuten mit 20 ml 37 %iger Salzsäure bei Raumtemperatur gerührt. Das Ge-. misch wird unter Eiskühlung in 100 ml 25 %iger Ammoniumhydroxydlösung eingegossen, der ausgefällte Niederschlag wird isoliert und an Kieselgel chromatographiert. Mit 37 - 48 % Aceton-Hexan erhält man 901 mg 2'-(4-Fluorphenyl)-11ß,17a,21-trihydroxy-2H'-2,4-pregnadieno-[3,2-c]pyrazol-20-on vom Schmelzpunkt 224° C.b) 3.5 g of the product obtained above are stirred for 3 minutes with 20 ml of 37% hydrochloric acid at room temperature. The GE-. Mix is poured into 100 ml of 25% ammonium hydroxide solution with ice cooling, the precipitate is isolated and chromatographed on silica gel. With 37-48% acetone-hexane, 901 mg of 2 '- (4-fluorophenyl) -11β, 17a, 21-trihydroxy-2H'-2,4-pregnadieno- [3,2-c] pyrazol-20-one is obtained melting point 224 ° C.
Beispiel 2Example 2

Eine Lösung von 1,7 g 2'-(4-Fluor-phenyl)-11ß,17α,21-trihydroxy-2H'-2,4-pregnadieno[3,2-c]pyrazol-20-on in 40 ml Methanol wird mit 800 mg Kupfer(II)-acetat Versetzt und 4 Stunden bei Raumtemporatur gerührt. Das Reaktionsgemisch wird mit Dichlomechan versetzt und mit verdünnter Ammoniumhydroxydiösung extrahiert. Die organische Phase wird mit Wasser gewaschen, über Natriumsulfat getrocknet und im Vakuum eingedampft. Der Rückstand besteht aus 1,8 g 2'-(4-Fluor-phenyl)-11ß,17α-dihydroxy-20-oxo-2H'-2,4- pregnadieno[3,2-c]pyrazol-21-al.A solution of 1.7 g of 2 '- (4-fluoro-phenyl) -11ß, 17α, 21-trihydroxy-2H'-2,4-pregnadieno [3,2-c] pyrazol-20-one in 40 ml of methanol 800 mg of copper (II) acetate are added and the mixture is stirred at room temperature for 4 hours. The reaction mixture is ver with dichlomechan sets and extracted with dilute ammonium hydroxide solution. The organic phase is washed with water, dried over sodium sulfate and evaporated in vacuo. The residue consists of 1.8 g of 2 '- (4-fluoro-phenyl) -11ß, 17α-dihydroxy-20-oxo-2H'-2,4-pregnadieno [3,2-c] pyrazol-21-al.

Beispiel 3Example 3

1,3 g des so hergestellten Aldehyds löst man in einem Gemisch aus 15 ml Dimethylformamid und 10 ml Methanol und versetzt nacheinander mit 4,5 g aktivem Mangan(IV)-oxid, 2,1 ml konzentrierter Essigsäure und 455 mg Kaliumcyanid. Die Reaktionsmischung wird 10 Minuten bei Raumtemperatur stark gerührt und anschließend übei eine Glasfilternutsche abgesaugt. Das Filtrat wird in Eiswasser eingerührt. Der entstandene Niederschlag wird mit Dichlormethan isoliert und an Kieselgel mit Aceton-Hexan chromatographiert. Ma erhält 251 mg 2'-(4-Fluor-phenyl)-11ß,17α-dihydroxy-20-oxo-2H'-2,4-pregnadieno[3,2-c]pyrazol-21-säure-methylester. Schmelzpunkt 192° C (umkristallisiert aus Aceton-Hexan).1.3 g of the aldehyde thus prepared are dissolved in a mixture of 15 ml of dimethylformamide and 10 ml of methanol, and 4.5 g of active manganese (IV) oxide, 2.1 ml of concentrated acetic acid and 455 mg of potassium cyanide are added in succession. The reaction mixture is stirred vigorously at room temperature for 10 minutes and then suction filtered through a glass suction filter. The filtrate is stirred into ice water. The resulting precipitate is isolated with dichloromethane and chromatographed on silica gel with acetone-hexane. Ma receives 251 mg of 2 '- (4-fluoro-phenyl) -11ß, 17α-dihydroxy-20-oxo-2H'-2,4-pregnadieno [3,2-c] pyrazole-21-acidic acid methyl ester. Melting point 192 ° C (recrystallized from acetone-hexane).

Beispiel 4Example 4

1,2 g 2'-(4-Fluor-phenyl)11ß,17α-dihydroxy-20-oxo-2H'-2,4-pregan- dieno[3,2-c]byrazol-21-al werden unter den im Beispiel lb beschriebenen Bedingungen, jedoch mit Butanol anstelle von Methand in 2'-(4-Fluor-phenyl)-11ß,17α-dihydroxy-20-oxo-2H'-2,4-pregna dieno[3,2-c]pyrazol-21-säure-butylester. Schmelzpunkt 150° C (umkristallisiert aus Aceton-Hexan).1.2 g of 2 '- (4-fluoro-phenyl) 11ß, 17α-dihydroxy-20-oxo-2H'-2,4-pregan- dieno [3,2-c] byrazole-21-al are among the im Example 1b conditions described, but with butanol instead of methane in 2 '- (4-fluorophenyl) -11ß, 17α-dihydroxy-20-oxo-2H'-2,4-pregna dieno [3,2-c] pyrazole -21-acid butyl ester. Melting point 150 ° C (recrystallized from acetone-hexane).

Claims (8)

1. Kortikoide der allgemeinen Formel I
Figure imgb0003
worin X zwei Wasserstoffatome und Y eine Hydroxy- oder Alkanoyloxygruppe oder X ein Sauerstoffatom und Y ein Wasserstoffatom, eine Hydroxy- gruppe oder eine Alkoxygruppe bedeuten. 1. Corticoids of the general formula I
Figure imgb0003
 wherein X two hydrogen atoms and Y a hydroxy or alkanoyloxy group or X represents an oxygen atom and Y represents a hydrogen atom, a hydroxyl group or an alkoxy group. 2. 2'-(4-Fluorphenyl)-11ß,17α,21-trihydroxy-2H-2,4-presnadieno-[3,2-c]pyrazol-20-on.2. 2 '- (4-fluorophenyl) -11ß, 17α, 21-trihydroxy-2H-2,4-presnadieno- [3,2-c] pyrazol-20-one. 3. 2'-(4-Fluor-phenyl)-11ß,17α-dihydroxy-20-oxo-2H'-2,4-pregna- dieno[3,2-c]pyrazol-21-al.3. 2 '- (4-fluorophenyl) -11β, 17α-dihydroxy-20-oxo-2H'-2,4-pregnadieno [3,2-c] pyrazole-21-al. 4. 2'-(4-Fluor-phenyl)-11ß,l7α-dihydroxy-20-oxo-2H'-2,4-pregna- dieno[3,2-c]pyrazol-21-saure-methylester.4. 2 '- (4-Fluoro-phenyl) -11ß, l7α-dihydroxy-20-oxo-2H'-2,4-pregnadieno [3,2-c] pyrazole-21-acidic acid methyl ester. 5. 2'-(4-Fluor-phenyl)-11ß,17α-dihydroxy-20-oxo-2H'-2,4-pngna dieno[3,2-c]pyrazol-21-säure-butylester.5. 2 '- (4-Fluoro-phenyl) -11ß, 17α-dihydroxy-20-oxo-2H'-2,4-pngna dieno [3,2-c] pyrazole-21-acid acid butyl ester. 6. Pharmazeutische Präparate, gekennzeichnet durch einen Gehalt eines oder mehrerer Kortikoide gemäß Anspruch 1 bis 5 als Wirkstoff.6. Pharmaceutical preparations, characterized by a content of one or more corticoids according to claims 1 to 5 as an active ingredient. 7. Methode zur Behandlung von Entzündungen, dadurch gekennzeichn daß man den Patienten ein pharmazeutisches Präparat gemäß. Anspruch 6 verabfolgt.7. Method for the treatment of inflammation, characterized in that the patient receives a pharmaceutical preparation according to. Claim 6 administered. 8. Verfahren zur Herstellung von Kortikoiden der allgemeinen Formel I
Figure imgb0004
worin X zwei Wasseratoffatome und Y eine Hydroxy- oder Alkanoyloxygruppe oder X ein Sauerstoffatom und Y ein Wasserstoffatom, eine Hydroxy gruppe oder eine Alkoxygruppe bedeuten, dadurch gokennzeit net, daß man in an sich bekannter Weise die Methylendioxygruppen einer Verbindung der allgemeinen Formel II
Figure imgb0005
 hydrolytisch abspaltet, gegebenenfalls die 21-Hydroxygruppe verestert oder zur Aldehy gruppe oxydiert und den erhaltenen Aldehyd in Gegenwart eines Alkohols mit Luftsauerstoff oder Mangan(IV)-oxyd oxydiert. 8. Process for the preparation of corticoids of the general formula I
Figure imgb0004
 wherein X two water atoms and Y a hydroxy or alkanoyloxy group or X represents an oxygen atom and Y represents a hydrogen atom, a hydroxyl group or an alkoxy group, thereby gokennzeit net that the methylenedioxy groups of a compound of general formula II
Figure imgb0005
 cleaved hydrolytically, if necessary the 21-hydroxy group esterified or oxidized to the aldehyde group and the aldehyde obtained oxidized in the presence of an alcohol with atmospheric oxygen or manganese (IV) oxide.
EP78100135A 1977-06-14 1978-06-12 New corticoids, process for their preparation and pharmaceutical compositions containing them Withdrawn EP0000471A1 (en)

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EP1496892A2 (en) * 2002-04-11 2005-01-19 Merck & Co., Inc. 1h-benzo(f)indazol-5-yl derivatives as selective glucocorticoid receptor modulators
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US7625920B2 (en) 2003-03-07 2009-12-01 Merck & Co., Inc. Fluorinated 4-azasteroid derivatives as androgen receptor modulators
WO2010147947A3 (en) * 2009-06-16 2011-03-03 Schering Corporation NOVEL [3,2-c] HETEROARYL STEROIDS AS GLUCOCORTICOID RECEPTOR AGONISTS, COMPOSITIONS AND USES THEREOF
CN102459306A (en) * 2009-04-03 2012-05-16 阿斯利康(瑞典)有限公司 Novel amide derivatives of steroidal[3,2-c]pyrazole compounds with glucocorticoid activity
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US7625937B2 (en) 2002-04-11 2009-12-01 Merck & Co., Inc. 1H-benzo[F]indazol-5-YL derivatives as selective glucocorticoid receptor modulators
JP2005528385A (en) * 2002-04-11 2005-09-22 メルク　エンド　カムパニー　インコーポレーテッド 1H-benzo [f] indazol-5-yl derivatives as selective glucocorticoid receptor modulators
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US7282591B2 (en) 2002-04-11 2007-10-16 Merck & Co., Inc. 1h-benzo{f}indazol-5-yl derivatives as selective glucocorticoid receptor modulators
EP1496892A2 (en) * 2002-04-11 2005-01-19 Merck & Co., Inc. 1h-benzo(f)indazol-5-yl derivatives as selective glucocorticoid receptor modulators
US7625920B2 (en) 2003-03-07 2009-12-01 Merck & Co., Inc. Fluorinated 4-azasteroid derivatives as androgen receptor modulators
US8163724B2 (en) 2007-10-04 2012-04-24 Astrazeneca Ab Glucocorticosteroids, processes for their preparation, pharmaceutical compositions containing them and their use in therapy
WO2009044200A1 (en) * 2007-10-04 2009-04-09 Astrazeneca Ab Steroidal [3, 2-c] pyrazole compounds, with glucocorticoid activity
AU2008306593B2 (en) * 2007-10-04 2012-04-12 Astrazeneca Ab Steroidal [3, 2-C] pyrazole compounds, with glucocorticoid activity
JP2010540612A (en) * 2007-10-04 2010-12-24 アストラゼネカ・アクチエボラーグ Steroid [3,2-C] pyrazole compounds having glucocorticoid activity
AU2008306593C1 (en) * 2007-10-04 2012-10-04 Astrazeneca Ab Steroidal [3, 2-C] pyrazole compounds, with glucocorticoid activity
CN102459306A (en) * 2009-04-03 2012-05-16 阿斯利康(瑞典)有限公司 Novel amide derivatives of steroidal[3,2-c]pyrazole compounds with glucocorticoid activity
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