EP1237903A1 - Derives de 11-beta-phenylestradiene ayant des groupes fluoro-alkyle dans la chaine laterale aromatique, leur production et des compositions pharmaceutiques contenant ces composes - Google Patents

Derives de 11-beta-phenylestradiene ayant des groupes fluoro-alkyle dans la chaine laterale aromatique, leur production et des compositions pharmaceutiques contenant ces composes

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Publication number
EP1237903A1
EP1237903A1 EP00988736A EP00988736A EP1237903A1 EP 1237903 A1 EP1237903 A1 EP 1237903A1 EP 00988736 A EP00988736 A EP 00988736A EP 00988736 A EP00988736 A EP 00988736A EP 1237903 A1 EP1237903 A1 EP 1237903A1
Authority
EP
European Patent Office
Prior art keywords
group
phenyl
methoxymethyl
methoxy
estra
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP00988736A
Other languages
German (de)
English (en)
Inventor
Ingo Tornus
Gerd Schubert
Günter Kaufmann
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Bayer Pharma AG
Original Assignee
Jenapharm GmbH and Co KG
Schering AG
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Jenapharm GmbH and Co KG, Schering AG filed Critical Jenapharm GmbH and Co KG
Publication of EP1237903A1 publication Critical patent/EP1237903A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
    • C07J1/0051—Estrane derivatives
    • C07J1/0081—Substituted in position 17 alfa and 17 beta
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/14—Drugs for genital or sexual disorders; Contraceptives for lactation disorders, e.g. galactorrhoea
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/38—Drugs for disorders of the endocrine system of the suprarenal hormones
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
    • C07J41/0033—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005
    • C07J41/0077—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 substituted in position 11-beta by a carbon atom, further substituted by a group comprising at least one further carbon atom
    • C07J41/0083—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 substituted in position 11-beta by a carbon atom, further substituted by a group comprising at least one further carbon atom substituted in position 11-beta by an optionally substituted phenyl group not further condensed with other rings

Definitions

  • the present invention relates to new 11 ⁇ -phenylestradiene derivatives with fluoroalkyl groups in the aromatic side chain, their preparation and pharmaceutical compositions containing these compounds.
  • the compounds according to the invention are for the treatment of diseases which are stimulated by cortisol or by corticides, to reduce the secreted cortisol , suitable for the stimulation of lactation, for the treatment of dysmenorrhea and fibroids, for the treatment of Cushing's disease and for cervical maturation, for the improvement of cognitive performance, for the treatment of endometriosis or for hormone replacement therapy (HRT)
  • diseases which are stimulated by cortisol or by corticides to reduce the secreted cortisol , suitable for the stimulation of lactation, for the treatment of dysmenorrhea and fibroids, for the treatment of Cushing's disease and for cervical maturation, for the improvement of cognitive performance, for the treatment of endometriosis or for hormone replacement therapy (HRT)
  • 11 ⁇ -substituted phenylestradienes are already known.
  • the preparation of 11 ⁇ -aryl-17 ⁇ -propionyl-estra-4,9-dienes is, for example, in patent specification EP 0 057 115 B, the reaction of 11 ⁇ - (4-formylphenyl) estra -4,9-d ⁇ en-3-ones with hydroxylamines described in the patent specification DE 3 504 421 A.
  • both the 11 ⁇ -formylphenyl group and the 3-keto group are oximated.
  • EP 0 411 733 11 ⁇ -aryl-gona-4,9-dien-3-ones are also known which describe various substituents in the 4-position of the 11 ⁇ -phenyl radical
  • EP 0 648 779 A describes 11-Benzaldox ⁇ m-17ß-methoxy-17-methoxymethyl-estrad ⁇ en-De ⁇ vate, where the hydrogen atom of the oxime group by the groups -COCH 3 , -COOC 2 H 5 , -CONH-phenyl, -CONHC 2 H 5 -COC 2 H 5 or -CO-phenyl is replaced.
  • These compounds are anti-gestagenic substances that have a significantly reduced antiglucorticoids compared to RU 486 possess vity
  • W represents a hydroxyl group, a Ci 6 -alkoxy group, a C ⁇ - 6 - alkylthio group, a halogen atom or a pseudohalogen
  • A represents an oxo group, an oximino group NOR 3 , a 1, 3-D ⁇ th ⁇ an- or a 1, 3-dithiolane group
  • R 3 is a hydrogen atom, a Ci S alkyl, aryl, alkylaryl or arylalkyl radical, a ds-acyl radical, a radical CONHR 4 , COSR 4 or COOR 4 means, where R 4 is a hydrogen atom or a Ci 8 alkyl, aryl, aralkyl or alkylaryl radical and n is an integer from 1 to 4, and their pharmaceutically acceptable salts
  • salts are alkali or alkaline earth metal salts, in particular sodium, potassium or ammonium salts
  • alkyl is understood to mean a branched or straight-chain alkyl radical. Examples include methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl or tert-butyl, n-Pentyl, i-pentyl, n-hexyl, 2-methylpentyl, 3-methylpentyl, 2,2-dimethylbutyl or 2,3-dimethylbutyl group called C n F 2n + ⁇ radical is a branched or straight-chain fluoroalkyl radical with 1 to 3 carbon atoms men understood, examples being a t ⁇ fluoromethyl, pentafluoroethyl, heptafluoro-n-propyl or heptafluoro-iso-propyl group
  • aryl is understood to mean a substituted or unsubstituted aryl radical having 5 or 10 carbon atoms.
  • Examples of an aryl radical are a phenyl group, a halophenyl group, a nitrophenyl group or a naphthyl group
  • aralkyl is understood to mean an arylalkyl radical having 6 to 15 carbon atoms.
  • examples of an arylalkyl radical are a free or aromatic substituted benzyl group, such as a benzyl group or halogenobenzyl group
  • alkylaryl is understood to mean an alkylaryl radical having 6 to 15 carbon atoms.
  • alkylaryl radical examples include a methylphenyl group, halomethylphenyl group, ethylphenyl group, dimethylphenyl group or methylphenyl group
  • halogen means a fluorine, chlorine, bromine or iodine atom
  • X preferably denotes a hydroxyl group. If X is a hydroxyl group, Y denotes a hydrogen atom or a t ⁇ fluoromethyl, pentafluoroethyl, heptafluoroisopropyl or heptafluoro-n-propyl group, preferably a t ⁇ fluoromethyl group
  • X and Y together can form an oxo group or a NOR 3 group, where R 3 is preferably a hydrogen atom, a methyl, ethyl, phenyl, tolyl, benzyl, formyl or acetyl group or a CONHR 4 radical, COSR 4 or COOR 4 , wherein R 4 preferably denotes a methyl or ethyl group, a phenyl group, a 4-fluorophenyl, tifluoromethylphenyl, tifluoromethoxymethyl, tifluoromethoxyphenyl or a benzyl group or a tolyl group.
  • R 3 preferably represents a hydrogen atom, a methyl, ethyl, phenyl, tolyl, benzyl, formyl or acetyl group or a radical CONHR 4 , COSR 4 or COOR 4 , where R 4 preferably represents a methyl or ethyl group, a phenyl group, a 4-fluorophenyl, a benzyl group or a tolyl group means Ri preferably means a methyl or ethyl group.
  • R 2 preferably represents a hydrogen atom or a Cj. 3 -alkyl radical, in particular a methyl or ethyl group.
  • Z represents a hydrogen atom, a C 6 alkyl radical, in particular a methyl or ethyl group, or a substituted methylene group CH 2 W, where W is a hydroxyl group, a C 6 alkoxy radical, in particular a methoxy group or an ethoxy group, a C ⁇ . 6 -Alkylthiorest, in particular a methylthio group or an ethylthio group, a halogen atom, such as a fluorine, chlorine, bromine or iodine atom, or a pseudohalogen, such as a cyanide or thiocyanide group.
  • R 1 and R 2 represent a methyl group
  • Z represents a CH 2 W group
  • W is a methoxy group
  • A represents an oxo group.
  • the invention further relates to a process for the regioselective introduction of fluoroalkyl groups into 11 ⁇ -phenylestradiene derivatives and their pharmaceutically acceptable salts according to the general formula (I), wherein 11 ⁇ -benzaldehydes of the general formula (II)
  • R-i has the meaning given above, with perfluoroalkylt ⁇ methylchlorosilanes to form fluoroalkylsilyl ethers (purple), hydrolyzed them to secondary alcohols of the general formula (IIIb) and
  • the invention also relates to pharmaceutical compositions which contain at least one 11 ⁇ -phenylestradiene derivative of the formula (I), optionally together with pharmaceutically acceptable auxiliaries and / or carriers.
  • These pharmaceutical compositions can be intended for subcutaneous, oral, buccal, rectal, implant, intravenous or intramuscular use. Together with conventional carriers, diluents and / or dyes, they contain at least one compound of the general formula (I) or its pharmaceutically acceptable salt.
  • Medicaments of the present invention are produced with the customary solid or liquid carriers and / or diluents and the generally customarily used auxiliaries in accordance with the desired type of application in a suitable dosage and in a manner known per se.
  • a suitable dosage form tablets, film-coated tablets, dragees, capsules, pills, powders, solutions or suspensions are preferably also prepared as a depot form.
  • parenteral dosage forms such as injection solutions or suppositories should be considered.
  • Pharmaceutical forms as tablets can, for example, by mixing the active ingredient with known excipients such as dextrose, sugar, sorbitol, mannitol, polyvinylpyrrolidone, disintegrants such as corn starch or alginic acid, binders such as starch or gelatin, lubricants such as magnesium stearate or talc and / or agents which achieve a depot effect can be obtained, such as carboxyl polymethylene, carboxymethyl cellulose, cellulose acetate phthalate or polyvinyl acetate.
  • the tablets can also consist of several layers or contain a score line.
  • Implants are produced by embedding them in polymers, for example, which can be injected under the skin and release the drug in the organism by diffusion from the polymer or by biodegradation of the polymer.
  • Coated tablets can furthermore be prepared by coating cores produced analogously to the tablets with agents conventionally used in tablet coatings, for example polyvinylpyrrolidone or shellac, gum arabic, talc, titanium dioxide, or sugar.
  • the coated tablet cover can also consist of several layers, for example using the above-mentioned auxiliaries.
  • solutions or suspensions with the active ingredient according to the invention can be mixed with substances such as saccharin, cyclamate or sugar and / or with flavoring substances such as vanillin or orange extract to improve the taste. Furthermore, they can be mixed with suspending aids, such as sodium carboxymethyl cellulose, or preservatives, such as p-hydroxybenzoic acid.
  • Capsules can be prepared by mixing the drug with carriers such as milk sugar or sorbitol, which are then introduced into the capsules. Suppositories are preferably produced by mixing the active ingredient with suitable carrier materials such as neutral fats or polyethylene glycols or their derivatives.
  • the pharmaceutical preparation forms can furthermore be transmucosal, buccal, sublingual or percutaneous preparation forms, e.g. Matrix formulations (adhesive matrix, liquid reservoir systems), transdermal therapeutic systems (TTS), gels, sprays, ointments or intranasal preparations such as nasal sprays or nasal drops.
  • Matrix formulations adheresive matrix, liquid reservoir systems
  • TTS transdermal therapeutic systems
  • gels e.g., sprays, ointments or intranasal preparations such as nasal sprays or nasal drops.
  • Suitable dosages for the compounds according to the invention are from 0.001 to 100 mg per day, depending on the body weight, age and constitution of the patient, it being possible for the necessary daily dose to be administered by single or multiple administration.
  • the 11 ⁇ -phenylestradiene derivatives according to the invention with fluoroalkyl groups in the aromatic side chain of the general formula (I) are compounds having an anti-hormonal effect.
  • compounds according to Table 1 are more strongly bound to the progestro receptor than to the glucocorticoid receptor, and are therefore better dissociated than the compound RU 38 486.
  • the compounds in animal experiments do not have an abortive effect at a dose of 1 mg per 4 days and in animals (rats) , Because of their reduced abortive and significantly more selective effects, they are particularly suitable for the treatment of endometriosis and for hormone replacement therapy with reduced potential for side effects.
  • Table 1 Receptor binding, preferably relative to progesterone receptor binding efficiencies (RBA values) in [%]
  • the compounds according to Table 2 are more strongly bound by the glucorticoid receptor versus progesterone receptor.
  • Such substances are suitable for the treatment of diseases which are stimulated by cortisol or by corticoids, such as diabetes, hypertension, depression, age-related memory loss (or age dementia), Cushings syndrome and they are also suitable for inhibiting the formation of cortisol and its effect (such as the stress-related secretion of cortisol) and for stimulating the increase in cognitive performance.
  • Table 2 Receptor binding, preferably relative to the glucocorticoid receptor Relative binding affinities (RBA values) in [ %]
  • Example 1 11ß- [4- (2,2,2-Trifluoro-1-hydroxyethyl) phenyl] -17ß-methoxy-17 ⁇ - (methoxymethyl) - estra-4,9-dien-3-one
  • a mixture of 2 g of 4- [17 ⁇ -methoxy-17 ⁇ - (methoxymethyl) -3-oxoestra-4,9-d ⁇ en-11 ⁇ -yl] benzaldehyde and 1 g of molecular sieve is dissolved in 30 ml of a mixture of absolute tetrahydrofuran and Absolute dimethylformamide (1 1, vv) suspended and 50 mg of tetrabutylammonium fluoride trihydrate are added while stirring. Then the mixture is cooled to 0 ° C. and slowly added dropwise.
  • Trifluoromethylt ⁇ methylsilane is slowly added to added 1 N hydrochloric acid and stirred for a further 3 h, diluted with water, added ethyl acetate and the phases were separated, the organic phase was washed with saturated aqueous sodium bicarbonate solution and then with saturated sodium chloride solution, dried over sodium sulfate and concentrated in vacuo to dryness The remaining foam is purified by flash chromatography on gravels. Reconstallation from diethyl ether / n-hexane gives 1.48 g 1 1ß- [4- (2,2,2-Tr ⁇ f!
  • a mixture of 1, 74 g of 4- (17ß-methoxy- (17 ⁇ -methoxymethyl) -3-oxoestra-4,9-d ⁇ en-1 1 ß-yljbenzaldehyde, 1 g of molecular sieve and 1 ml of heptafluoropropylt ⁇ methylsilane are suspended in 30 ml of absolute tetrahydrofuran and with stirring at -20 ° C. with 100 mg of tetramethylammonium fluoride trihydrate.
  • the mixture is warmed slowly to room temperature, stirred for a further 12 h, filtered and evaporated to dryness in vacuo.
  • Example 8 4- [17ß-Methoxy-17 ⁇ - (methoxymethyl) -3-oxaestra-4,9-dien-11ß-yl] phenyl-2,2,2-trifluoro-ethan-1-one- (Z) - [ N- (4-fluoro-phenylamino) carbonyl] oxime
  • Example 9 4- [17ß-Methoxy-17 ⁇ - (methoxymethyl) -3-oxoestra-4,9-dien-11ß-yl] phenyl-2,2,2-trifluoro-ethan-1-one- (Z) - [N- (ethylamino) carbonyl] oxime
  • Example 10 4- [17 ⁇ -Methoxy-17 ⁇ - (methoxymethyl) -3-oxaestra-4,9-dien-11 ⁇ -yl] phenyl-2,2,2-trifluoroethan-1 -one - (Z) - ( O-acetyl) oxime
  • the crude product is purified by means of preparative layer chromatography on silica gel 60 PF 254 + 3 66nm. 228 mg of 4- [17 ⁇ -methoxy-17 ⁇ - (methoxymethyl) -3-oxoestra-4,9-dien-11ß-yl] -2,2,2-thfluoroethan-1-one- (Z) - [0 - (ethylmercapto) carbonyl] oxime as a colorless foam.
  • the target connection is made according to Example 3.
  • Example 18 11ß- ⁇ 4- [2,2,2-Trifluoro-1-hydroxy-1- (trifluoromethyl) ethyl] phenyl ⁇ -17ß-methoxy-17 ⁇ -
  • Glucocorticoid receptor Thymus cytosol of the adrenalectomized rat. Thymi stored at -30 ° C. Buffer: TED buffer. Tracer: 3 H-dexamethasone, 20nM. Reference substance: dexamethasone.
  • the bound and free steroid were separated by mixing in activated carbon / dextran (1% / 0.1%), centrifuging and measuring the receptor-bound 3 H Activity in the supernatant. From measurements in series of concentrations were the IC 5 o determined for the reference substance and for the compound to be tested and as the quotient of both values determined (x 100%), the relative molar binding affinity (RBA).

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  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Endocrinology (AREA)
  • Diabetes (AREA)
  • Reproductive Health (AREA)
  • Gynecology & Obstetrics (AREA)
  • Pregnancy & Childbirth (AREA)
  • Urology & Nephrology (AREA)
  • Steroid Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne de nouveaux dérivés de 11-β-phénylestradiène ayant des groupes fluoro-alkyle dans la chaîne latérale aromatique, leur procédé de production et les préparations pharmaceutiques contenant ces composés. L'invention concerne de nouveaux dérivés de 11-β-Phénylestradiène ayant, dans la chaîne latérale aromatique, des groupes fluoro-alkyle, de la formule générale (I), leur production et les préparations pharmaceutiques contenant ces composés. Les composés selon l'invention sont appropriés au traitement de maladies stimulées par le cortisol ou des corticoïdes, à la réduction de cortisol sécrété, à la stimulation de la lactation, au traitement de la dysménorrhée et de myomes, au traitement de Morbus Cushing et à la maturation du col, à l'amélioration des capacités cognitives, au traitement de l'endométriose ou pour le traitement hormonal substitutif (HRT).
EP00988736A 1999-12-15 2000-11-21 Derives de 11-beta-phenylestradiene ayant des groupes fluoro-alkyle dans la chaine laterale aromatique, leur production et des compositions pharmaceutiques contenant ces composes Withdrawn EP1237903A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE19961219 1999-12-15
DE19961219A DE19961219A1 (de) 1999-12-15 1999-12-15 11beta-Phenylestratrien-Derivate mit Fluoralkylgruppen in der aromatischen Seitenkette, deren Herstellung und diese Verbindungen enthaltende pharmazeutische Zusammensetzungen
PCT/EP2000/011556 WO2001044267A1 (fr) 1999-12-15 2000-11-21 DERIVES DE 11-$G(b)-PHENYLESTRADIENE AYANT DES GROUPES FLUORO-ALKYLE DANS LA CHAINE LATERALE AROMATIQUE, LEUR PRODUCTION ET DES COMPOSITIONS PHARMACEUTIQUES CONTENANT CES COMPOSES

Publications (1)

Publication Number Publication Date
EP1237903A1 true EP1237903A1 (fr) 2002-09-11

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ID=7933253

Family Applications (1)

Application Number Title Priority Date Filing Date
EP00988736A Withdrawn EP1237903A1 (fr) 1999-12-15 2000-11-21 Derives de 11-beta-phenylestradiene ayant des groupes fluoro-alkyle dans la chaine laterale aromatique, leur production et des compositions pharmaceutiques contenant ces composes

Country Status (5)

Country Link
EP (1) EP1237903A1 (fr)
JP (1) JP2003517001A (fr)
AU (1) AU2507601A (fr)
DE (1) DE19961219A1 (fr)
WO (1) WO2001044267A1 (fr)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1285927A3 (fr) 2001-08-16 2005-06-29 Schering Aktiengesellschaft Utilisation d'antagonistes du récepteur glucocorticoide pour la prévention et traitement des maladies de la fonction reproductive masculine
EP1525215B1 (fr) * 2002-08-02 2006-09-06 Schering Aktiengesellschaft Modulateurs de recepteurs de progesterone presentant une activite antigonadotrope augmentee, destines au controle de fertilite et au traitement hormonal substitutif chez la femme
DE10236405A1 (de) * 2002-08-02 2004-02-19 Schering Ag Progesteronrezeptormodulatoren mit erhöhter antigonadotroper Aktivität für die weibliche Fertilitätskontrolle und Hormonersatztherapie
PT1601363E (pt) * 2003-03-11 2012-08-17 Trophos Aplicação como medicamentos de derivados da colest-4-en-3- ona, composições farmacêuticas que os contêm e novos derivados

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3504421A1 (de) * 1985-02-07 1986-08-07 Schering AG, 1000 Berlin und 4709 Bergkamen Neue 11ss-phenyl-gonane, deren herstellung und diese enthaltende pharmazeutische praeparate
GB8513723D0 (en) * 1985-05-31 1985-07-03 Erba Farmitalia 11-beta substituted steroids
FR2586021B1 (fr) * 1985-08-09 1988-10-14 Roussel Uclaf Nouveaux produits derives de la structure 5a-oh d 9(10) 19-nor steroides
DE3621024C2 (de) * 1986-06-20 1999-10-28 Schering Ag 11beta-Phenylestradiene, deren Herstellung und diese enthaltende pharmazeutische Präparate
DK72693D0 (da) * 1993-06-18 1993-06-18 Lundbeck & Co As H Compounds
DE4332284C2 (de) * 1993-09-20 1997-05-28 Jenapharm Gmbh 11-Benzaldoxim-17beta-methoxy-17alpha-methoxymethyl-estradien-Derivate, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel
DE4332283A1 (de) * 1993-09-20 1995-04-13 Jenapharm Gmbh Neue 11-Benzaldoximestradien-Derivate, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel
IL122740A (en) * 1997-01-15 2003-09-17 Akzo Nobel Nv 16-hydroxy-11-(substituted phenyl)-estra-9,4-diene derivatives, their preparation and pharmaceutical compositions containing them

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO0144267A1 *

Also Published As

Publication number Publication date
JP2003517001A (ja) 2003-05-20
AU2507601A (en) 2001-06-25
WO2001044267A1 (fr) 2001-06-21
DE19961219A1 (de) 2001-07-19

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