WO2001018028A1 - Novel c13-substituted estra-1,3,5(10)-triene-3-yl-sulfamates, a method for producing the same and pharmaceutical compositions containing these compounds for inhibiting oestrone sulfatase - Google Patents
Novel c13-substituted estra-1,3,5(10)-triene-3-yl-sulfamates, a method for producing the same and pharmaceutical compositions containing these compounds for inhibiting oestrone sulfatase Download PDFInfo
- Publication number
- WO2001018028A1 WO2001018028A1 PCT/EP2000/008374 EP0008374W WO0118028A1 WO 2001018028 A1 WO2001018028 A1 WO 2001018028A1 EP 0008374 W EP0008374 W EP 0008374W WO 0118028 A1 WO0118028 A1 WO 0118028A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- sulfamate
- estra
- homo
- trien
- acetyl
- Prior art date
Links
- 0 C[C@@](*I)C=C(CC(*)C(C1C(*)C2)C3(*)C2(*)[C@@](*)(**)C(*)C3*)C1=CC(*)=C Chemical compound C[C@@](*I)C=C(CC(*)C(C1C(*)C2)C3(*)C2(*)[C@@](*)(**)C(*)C3*)C1=CC(*)=C 0.000 description 1
Classifications
-
- 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
- C07J41/0072—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 the A ring of the steroid being aromatic
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- A61P5/32—Antioestrogens
Definitions
- the invention relates to new Estra-1, 3,5 (10) -trien-3-yl sulfamates which, in the C 13 position, contain a C 2 -C 5 alkyl, C 2 -C alkenyl or C 2 - C 5 alkynyl and have an acyl, oxycarbonyl, aminocarbonyl, sulfonyl or aminosulfonyl radical on the nitrogen atom of the sulfamate group.
- the invention also relates to processes for the preparation of the compounds according to the invention and pharmaceutical compositions which contain these compounds.
- the compounds according to the invention have proven to be steroid sulfatase inhibitors which do not have an estrogenic effect.
- estrogens are primarily synthesized and secreted by the ovaries. Accordingly, in sexually mature women, the blood levels of estradiol, estrone and estrone sulfate fluctuate over the course of the cycle. In human pregnancy, the placenta secretes much higher amounts of estrogen than the ovary. In addition to these estrogen sources, peripheral estrogen sources play a role in the human organism, which are of primary importance when ovarian estrogen secretion has ceased or has not yet been established. These estrogen sources have also been shown to be of great physiological importance for the male sex.
- BEST ⁇ TIGUMGSKOPIE found that factor 50-300 times higher estrogen levels were generated in breast cancer via sulfatase activity (cleavage of estrone sulfate) than via aromatase (Pasqualini JR et al., Estrone sulfatase versus estrone sulfotransferase in human breast cancer: potential clinical applications. J. Steroid Biochem. And Mol. Biol. 69 (1999) 287-292). Similar findings were also made by other groups. In breast tissue, 10-fold more estrone is generated from androstenedione via sulfatase than from aromatase.
- sulfatase inhibitors can very effectively inhibit the growth of estrogen-dependent tumors, since they greatly reduce the estrogen concentration in the tumor tissue itself.
- sulfatase inhibitors are therefore increasingly being sought which are not themselves estrogenic and, as a result of the hydrolysis, do not give rise to any estrogenic products.
- 2-methoxy-estrone-3-O-sulfamate is a potent sulfatase inhibitor which has no estrogenic effect on uterine growth in ovariectomized rats.
- Estrone-3-O-sulfamates are also described as sulfatase inhibitors in WO 93/05064.
- the Estro ⁇ -3-O-sulfamate unsubstituted by nitrogen is a strong sulfatase inhibitor (cf. Horwarth et al. In J. Med. Chem. 1994, 37, pp. 219-221, in particular Fig. 3 on page 220).
- this substance also shows strong estrogenic effects as described by Elger W. et al. in J. Steroid Biochem. Mol. Biol. 55 (1995), pp. 395-403.
- Further estrone-3-O-sulfamates are disclosed as sulfatase inhibitors in WO 99/33858. These compounds have essentially no estrogenic activity.
- Sulfamoyloxy compounds with more than one sulfamate group in the molecule in particular those which are sulfamoylated at the positions characteristic of the estrogenic action, including substituents or side chains (e.g. in the 7- and / or 11-position), which can be located on the periphery of the steroid structure, a significant increase in Have sulfatase activity with reduced estrogenic activity.
- 3,17-disulfamoyloxydef ⁇ vate show good sulfatase activity.
- monosulfamates also have good sulfatase inhibition with low estrogenicity, with the exception of the ring A sulfamates.
- Ring A sulfamates are known from WO 97/14712 - as mentioned above - as compounds with a pronounced strong estrogenic action.
- the object of the present invention was to provide further steroid sulfatase inhibitors which themselves have no estrogenic action and which, as a result of the hydrolysis, do not give any estrogenic products.
- R 2 is hydrogen, d-Cio-alkyl, -CC 10 alkoxyalkyl, C 3 -C 0 cycloalkyl, C 2 -C 10 -
- R 3 represents H or R, R 4 -CC 7 alkyl, d-dy-haloalkyl, C 2 -C 17 alkenyl, C 2 -C 7 alkynyl, C 3 -C 10 -
- R 5 , R 6 independently of one another are hydrogen, dC 5 -alkyl, dC 5 -haloalkyl, aryl, aryl-dC 3 -alkyl, -C-C 3 -alkylaryl or together with the nitrogen atom to which they are bound, a polymethyleneimino radical Form 2-6 carbon atoms or a morpholino radical
- R 7 , R 9 independently of one another are H, OH, halogen, dC 5 alkoxy or dC 5 - haloalkoxy
- R 8 is H, OH, d-Cs-alkyl, Ci-d- haloalkyl, C 2 -C 5 alkenyl, C 2 -C 5 alkynyl, or
- Is halogen, Rio, R11 are hydrogen or R 10 and Rn together represent a CH 2 group
- R ⁇ 2 , R ⁇ 3 , ⁇ 4 independently of one another are H, OH, CC 5 alkoxy or C 1 -C 5 haloalkoxy, or R 12 is halogen, or
- physiologically compatible salts are alkali or alkaline earth salts, in particular sodium, potassium or ammonium salts.
- Usual physiologically compatible inorganic or organic acids with which free hydroxyl groups of the compounds of the general formula I can be esterified examples are phosphoric acid, sulfuric acid, oxalic acid, maleic acid, fumaric acid, lactic acid, tartaric acid, malic acid, citric acid, salicylic acid, adipic acid and benzoic acid.
- alkyl means a branched or unbranched hydrocarbon chain.
- Haloalkyl correspondingly means a mono- or polysubstituted, branched or unbranched hydrocarbon chain.
- Alkenyl means a branched or unbranched hydrocarbon chain with at least one double bond.
- Alkynyl means a branched or unbranched hydrocarbon chain with at least one triple bond.
- Alkoxy means a branched or unbranched carbon chain which is interrupted by one or more oxygen atoms.
- the alkoxy radical can be substituted one or more times with halogen.
- aryl stands for a phenyl radical, which can be optionally substituted, or for a heteroaryl radical, for example for pyridine, picoline, lutidine, collidine, quinoline, acridine, pyridazine, pyrimidine, pyrazine, triazine, pterins, pyrrole, indole, pyrazole , Imidazole, 1, 2,3-thazole, 1, 2,4-triazole, tetrazole, oxazole, thiazole, thiodiazole.
- R 2 is hydrogen.
- R 1 very particularly preferably denotes the acyl radical -COR 3 .
- R15 stands for ethyl or propyl.
- Very particularly preferred compounds of the invention are the following:
- the strong sulfatase-inhibiting activity of the compounds 0 according to the invention manifests itself in a reduced cleavage of oestrone sulfate in organs and tissues of ovariectomized rats. Characteristically, the rate of toluene extractable metabolites of oestrone sulfate in the blood is also greatly reduced.
- the activity profile of the compounds according to the invention therefore allows them to be used for the production of medicaments for the treatment of estrogen-dependent diseases, namely 5 for all therapies in which the sulfatase activity is to be inhibited and an estrogenic side reaction is undesirable.
- An example is the treatment of estrogen-dependent tumor diseases.
- the present invention therefore also relates to pharmaceutical compositions which contain at least one compound of the general formula I, optionally together with pharmaceutically acceptable auxiliaries and / or carriers.
- These pharmaceutical compositions and medicaments can be intended for oral, rectal, vaginal, subcutaneous, percutaneous, intravenous or intramuscular application.
- they contain at least one compound of the general formula I.
- the medicaments of the invention are known with the usual solid or liquid carriers or diluents and the commonly used pharmaceutical-technical auxiliaries in accordance with the desired type of application with a suitable dosage in a known manner Manufactured way.
- the preferred preparations are in a dosage form which is suitable for oral administration. Such forms of administration are, for example, tablets, film-coated tablets, dragees, capsules, pills, powders, solutions or suspensions or even depot forms.
- parenteral preparations such as injection solutions are also suitable.
- Suppositories and agents for vaginal use may also be mentioned as preparations.
- Corresponding tablets can be obtained, for example, by mixing the active ingredient with known auxiliaries, for example inert diluents 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 to achieve one Depot effects such as carboxylpolymethylene, carboxylmethylcellulose, cellulose acetate phthalate or polyvinyl acetate can be obtained.
- auxiliaries for example inert diluents 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 to achieve one Depot effects such as carboxyl
- Coated tablets can accordingly be produced by coating cores produced analogously to the tablets with agents commonly used in tablet coatings, for example polyvinylpyrrolidone or shellac, gum arabic, talc, titanium oxide or sugar.
- the coated tablet can also consist of several layers, wherein the auxiliaries mentioned above for the tablets can be used.
- Solutions or suspensions with the compounds of the general formula I according to the invention can additionally taste-improving agents such as saccharin, Cyclamate or sugar and z.
- B. contain flavorings such as vanillin or orange extract. They can also contain suspending agents such as sodium carboxymethyl cellulose or preservatives such as p-hydroxybenzoates.
- Capsules containing the compounds of general formula I can be prepared, for example, by mixing the compound (s) of general formula I with an inert carrier such as milk sugar or sorbitol and encapsulating them in gelatin capsules.
- an inert carrier such as milk sugar or sorbitol
- Suitable suppositories can be produced, for example, by mixing them with carriers such as neutral fats or polyethylene glycol or their derivatives.
- Suitable dosages for the compounds according to the invention are from 0.001 to 10 mg per day, depending on the body weight, age and constitution of the patient, it being possible for the necessary daily dose to be applied by single or multiple administration.
- Another object of the invention is the process for the preparation of the compounds of general formula I according to the invention
- Example 4 363 mg of the sulfamate obtained in Example 1 a were dissolved in a mixture of 5 ml of pyndine and 5 ml of dichloromethane. With stirring, 3.63 g of stearic acid chloride were added to this solution. Stirring was continued for 22 hours at room temperature, then 10 ml of water were added with ice cooling and stirred for a further 24 hours at room temperature. The organic phase was separated off and washed successively with 2N aqueous hydrochloric acid, water, 2N aqueous potassium hydroxide solution and water. After drying over anhydrous sodium sulfate, the extract was concentrated in a vacuum rotary evaporator. The title compound was obtained as a light yellow foam Example 4
- Ovariectomized adult rats are treated orally with dosages of the compound according to the invention between 1-300 ⁇ g. 24 hours after application, leukocyte and organ homogenates of these animals are examined for their ability to split oestrone sulfate.
- the substances according to the invention inhibit the hydrolysis of oestrone sulfate in the dose range between 50-90%. If animals are treated with oestrone sulfate 24 hours after treatment with a substance according to the invention, its hydrolysis products can be extracted from the plasma after one hour. Substances according to the invention reduce the extracted fraction by approximately 75%.
Abstract
Description
Claims
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP00967631A EP1212346A1 (en) | 1999-09-08 | 2000-08-28 | Novel c13-substituted estra-1,3,5(10)-triene-3-yl-sulfamates, a method for producing the same and pharmaceutical compositions containing these compounds |
AU77739/00A AU7773900A (en) | 1999-09-08 | 2000-08-28 | Novel c13-substituted estra-1,3,5(10)-triene-3-yl-sulfamates, a method for producing the same and pharmaceutical compositions containing these compounds |
JP2001522251A JP2003508542A (en) | 1999-09-08 | 2000-08-28 | Novel C13-substituted estra-1,3,5 (10) -trien-3-yl-sulphamate, process for producing the same and pharmaceutical composition containing the compound |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19943708A DE19943708B4 (en) | 1999-09-08 | 1999-09-08 | New C13-substituted Estra-1,3,5 (10) -trien-3-yl-sulfamates, processes for their preparation and pharmaceutical compositions containing them |
DE19943708.4 | 1999-09-08 |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2001018028A1 true WO2001018028A1 (en) | 2001-03-15 |
WO2001018028A8 WO2001018028A8 (en) | 2001-06-07 |
Family
ID=7921778
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP2000/008374 WO2001018028A1 (en) | 1999-09-08 | 2000-08-28 | Novel c13-substituted estra-1,3,5(10)-triene-3-yl-sulfamates, a method for producing the same and pharmaceutical compositions containing these compounds for inhibiting oestrone sulfatase |
Country Status (5)
Country | Link |
---|---|
EP (1) | EP1212346A1 (en) |
JP (1) | JP2003508542A (en) |
AU (1) | AU7773900A (en) |
DE (1) | DE19943708B4 (en) |
WO (1) | WO2001018028A1 (en) |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2004074308A1 (en) * | 2003-02-19 | 2004-09-02 | Schering Aktiengesellschaft | Antitumoral 18a-homoestra-1,3,5(10)-trien-3-yl 2-substituted sulfamates |
WO2004074307A1 (en) * | 2003-02-19 | 2004-09-02 | Schering Aktiengesellschaft | 2-substituted estra-1,3,5(10)-triene-3-yl sulfamate with an anti-tumour action |
DE10307103A1 (en) * | 2003-02-19 | 2004-09-09 | Schering Ag | Anti-tumor effective 2-substituted D-homostra-1,3,5 (10) -trien-3-yl sulfamate |
US6953785B2 (en) | 2000-04-24 | 2005-10-11 | Kyowa Hakko Kogyo Co., Ltd. | Estra-1,3,5(10)-triene derivatives |
US8026229B2 (en) | 2001-08-13 | 2011-09-27 | Sterix Limited | Antitumor-active 2-alkoxyestradiol sulfamates |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE19540233A1 (en) * | 1995-10-19 | 1997-04-24 | Jenapharm Gmbh | Sulfamate derivatives of 1,3,5 (10) estratriene derivatives, processes for their preparation and pharmaceutical compositions containing these compounds |
US5705495A (en) * | 1995-10-19 | 1998-01-06 | Jenapharm Gmbh & Co. Kg. | Sulfamate derivatives of 1,3,5(10)-estratriene derivatives, methods for their production and pharmaceuticals containing these compounds |
DE19712488A1 (en) * | 1997-03-25 | 1998-10-01 | Knoell Hans Forschung Ev | Steroid sulfamates, processes for their preparation and use thereof |
-
1999
- 1999-09-08 DE DE19943708A patent/DE19943708B4/en not_active Expired - Fee Related
-
2000
- 2000-08-28 AU AU77739/00A patent/AU7773900A/en not_active Abandoned
- 2000-08-28 WO PCT/EP2000/008374 patent/WO2001018028A1/en not_active Application Discontinuation
- 2000-08-28 EP EP00967631A patent/EP1212346A1/en not_active Ceased
- 2000-08-28 JP JP2001522251A patent/JP2003508542A/en not_active Abandoned
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE19540233A1 (en) * | 1995-10-19 | 1997-04-24 | Jenapharm Gmbh | Sulfamate derivatives of 1,3,5 (10) estratriene derivatives, processes for their preparation and pharmaceutical compositions containing these compounds |
US5705495A (en) * | 1995-10-19 | 1998-01-06 | Jenapharm Gmbh & Co. Kg. | Sulfamate derivatives of 1,3,5(10)-estratriene derivatives, methods for their production and pharmaceuticals containing these compounds |
DE19712488A1 (en) * | 1997-03-25 | 1998-10-01 | Knoell Hans Forschung Ev | Steroid sulfamates, processes for their preparation and use thereof |
Non-Patent Citations (6)
Title |
---|
AHMED S ET AL: "Derivation of a possible transition-state for the reaction catalysed by the enzyme Estrone Sulfatase (ES)", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,GB,OXFORD, vol. 9, no. 12, 21 June 1999 (1999-06-21), pages 1645 - 1650, XP004167732, ISSN: 0960-894X * |
ANSTEAD G M ET AL: "The estradiol pharmacophore: Ligand structure-estrogen receptor binding affinity relationships and a model for the receptor binding site", STEROIDS: STRUCTURE, FUNCTION, AND REGULATION,US,ELSEVIER SCIENCE PUBLISHERS, NEW YORK, NY, vol. 62, no. 3, 1 March 1997 (1997-03-01), pages 268 - 303, XP004057108, ISSN: 0039-128X * |
DATABASE CHEMABS [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; SOROKINA, I. B. ET AL: "Estrogen and antineoplastic activity in a series of transformed estrone and estradiol analogs", XP002160075, retrieved from STN Database accession no. 80:91450 * |
IZV. AKAD. NAUK SSSR, SER. BIOL. (1973), (5), 664-70 * |
SCHWARZ S ET AL: "Synthesis of estrogen sulfamates: Compounds with a novel endocrinological profile", STEROIDS: STRUCTURE, FUNCTION, AND REGULATION,US,ELSEVIER SCIENCE PUBLISHERS, NEW YORK, NY, vol. 61, no. 12, 1 December 1996 (1996-12-01), pages 710 - 717, XP004016631, ISSN: 0039-128X * |
WOO L W L ET AL: "Oestrone 3-O-(N-acetyl)sulphamate, a potential molecular probe of the active site of oestrone sulphatase", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,GB,OXFORD, vol. 7, no. 24, 16 December 1997 (1997-12-16), pages 3075 - 3080, XP004136588, ISSN: 0960-894X * |
Cited By (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6953785B2 (en) | 2000-04-24 | 2005-10-11 | Kyowa Hakko Kogyo Co., Ltd. | Estra-1,3,5(10)-triene derivatives |
US8026229B2 (en) | 2001-08-13 | 2011-09-27 | Sterix Limited | Antitumor-active 2-alkoxyestradiol sulfamates |
DE10307103A1 (en) * | 2003-02-19 | 2004-09-09 | Schering Ag | Anti-tumor effective 2-substituted D-homostra-1,3,5 (10) -trien-3-yl sulfamate |
WO2004074308A1 (en) * | 2003-02-19 | 2004-09-02 | Schering Aktiengesellschaft | Antitumoral 18a-homoestra-1,3,5(10)-trien-3-yl 2-substituted sulfamates |
DE10307104A1 (en) * | 2003-02-19 | 2004-09-23 | Schering Ag | Anti-tumor effective 2-substituted Estra-1,3,5 (10) -trien-3-yl sulfamate |
DE10307103A8 (en) * | 2003-02-19 | 2004-12-16 | Schering Ag | Antitumor effective 2-substituted D-homoestra-1,3,5 (10) -trien-3-yl sulfamate |
DE10307105A1 (en) * | 2003-02-19 | 2004-09-09 | Schering Ag | Antitumor active 2-substituted 18a-homoestra-1,3,5 (10) -trien-3-yl sulfamate |
JP2006517947A (en) * | 2003-02-19 | 2006-08-03 | シエーリング アクチエンゲゼルシャフト | Antitumor activity 2-substituted 18a-homoestradi-1,3,5 (10) -trien-3-ylsulfamate |
JP2006517945A (en) * | 2003-02-19 | 2006-08-03 | シエーリング アクチエンゲゼルシャフト | Antitumor activity 2-substituted estra-1,3,5 (10) -trien-3-ylsulfamate |
US7427610B2 (en) | 2003-02-19 | 2008-09-23 | Sterix Limited | 2-substituted estra-1,3,5(10)-triene-3-yl sulfamate with an anti-tumour action |
USRE42132E1 (en) | 2003-02-19 | 2011-02-08 | Sterix Limited | Antitumoral D-homoestra-1,3,5(10)-trien-3-yl 2-substituted sulfamates |
WO2004074307A1 (en) * | 2003-02-19 | 2004-09-02 | Schering Aktiengesellschaft | 2-substituted estra-1,3,5(10)-triene-3-yl sulfamate with an anti-tumour action |
JP4933250B2 (en) * | 2003-02-19 | 2012-05-16 | ステリックス リミティド | Antitumor activity 2-substituted estra-1,3,5 (10) -trien-3-ylsulfamate |
US8492570B2 (en) | 2003-02-19 | 2013-07-23 | Sterix Limited | 2-substituted estra-1,3,5(10)-triene-3-yl sulfamate with an anti-tumor action |
Also Published As
Publication number | Publication date |
---|---|
AU7773900A (en) | 2001-04-10 |
DE19943708B4 (en) | 2007-12-20 |
DE19943708A1 (en) | 2001-03-15 |
EP1212346A1 (en) | 2002-06-12 |
WO2001018028A8 (en) | 2001-06-07 |
JP2003508542A (en) | 2003-03-04 |
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