EP0437552A1 - Derives alcoyles en 17/21 de la 19-nor progesterone - Google Patents
Derives alcoyles en 17/21 de la 19-nor progesteroneInfo
- Publication number
- EP0437552A1 EP0437552A1 EP90907142A EP90907142A EP0437552A1 EP 0437552 A1 EP0437552 A1 EP 0437552A1 EP 90907142 A EP90907142 A EP 90907142A EP 90907142 A EP90907142 A EP 90907142A EP 0437552 A1 EP0437552 A1 EP 0437552A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- general formula
- pregna
- compounds
- methyl
- ethyl
- 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- Withdrawn
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J7/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J7/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms
- C07J7/0005—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21
- C07J7/001—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group
- C07J7/004—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group substituted in position 17 alfa
Definitions
- the present invention relates to the field of therapeutic chemistry and in particular steroid chemistry.
- R 'and R " identical or different, represent hydrogen or a lower alkyl radical, having from 1 to 3 carbon atoms, in straight or branched chain
- R 1 represents a lower alkyl radical, identical or different from R 'or R ", having from 1 to 6 carbon atoms in a straight or branched chain.
- R ′ and R ′′ are preferably a methyl, ethyl or isopropyl radical. They can also be a propyl radical.
- progestogen molecules cf. French patent 2,077,877
- progestogen molecules such as for example 3,20- dioxo 17 ⁇ -methyl 19-nor pregna 4,9-diene.
- the object of the present invention is to provide new compounds of general formula I, possessing very advantageous progestomimetic properties, links to improved progesterone receptors and slower hepatic metabolism.
- Ac is the acyl residue of an organic carboxylic acid having from 1 to 4 carbon atoms
- the wavy line indicates a spatial orientation ⁇ or ⁇
- ring A is fully aromatic type 3 alkyloxy
- the strong base can be an alkaline alcoholate derived from a lower alcohol of 1 to 5 linear or branched carbon atoms and from a metal such as lithium, sodium or potassium, such as for example sodium teramylate, terbutylate of potassium, sodium ethanolate, an alkali or alkaline earth amide, lithium, potassium sodium, calcium or barium.
- a metal such as lithium, sodium or potassium, such as for example sodium teramylate, terbutylate of potassium, sodium ethanolate, an alkali or alkaline earth amide, lithium, potassium sodium, calcium or barium.
- sodium amide or lithium isopropylamide is used. Dimsyl sodium can also be used.
- the alkylating agent can be a dialkyl sulphate, such as dimethyl sulphate for example, or an alkyl halide, the halogen possibly being iodine or bromine.
- the solvent can be alone or a mixture chosen from the list: liquid ammonia, ether, THF, benzene, toluene, hexane, alcohol, the preferred solvents being liquid ammonia and tetrahydrofuran.
- the strong base and the alkylating agent are used in excess relative to the stoichiometry.
- the reaction is followed by acid hydrolysis.
- the compounds of general formula III, mono or polyalkyls are optionally purified by appropriate means such as for example by crystallization or by chromatography on a column consisting of an adsorbent suitable for chromatography such as silica, talc or magnesium silicate or alumina.
- the reaction temperature can vary widely between -60 ° and + 50 ° C. It is preferably between -60 ° and -40o, due to the preferred use of ammonia as solvent.
- a lower concentration of basic agent from 4 to 7 equivalents
- a lower concentration of alkylating agent are preferably used.
- lithium isopropylamide is the best reagent for alkylation at 21.
- the alkaline alcoholates promote alkylation at 17, the basic reagent preferred in this case is the metallic amide resulting from the attack " in situ "of liquid ammonia with an alkali or alkaline-earth metal such as lithium or calcium.
- Alkylation to 17 ⁇ from an alkaline enolate is a difficult reaction and requires the presence of a very large excess of basic agent.
- methyl at 21 by the alkylating agent is more difficult when position 17 is already occupied by an alkyl group.
- a mixture of mono- and dialkylated derivatives at 21- is obtained and therefore requires a large excess of metal and alkylating agent.
- Monoalkylation is promoted at 21 using a basic agent such as lithium isopropylamide in tetrahydrofuran due to the steric hindrance of this basic reagent.
- reaction can be written as follows for an ethylation reaction:
- R, R 1 and R 2 are defined as above
- the reduction according to Birch-Nielsen is carried out in an inert solvent such as a cyclic or linear ether by means of an alkali metal in solution in liquid ammonia in the presence of a proton donor agent such as for example an alkanol such as methanol or ethanol.
- a proton donor agent such as for example an alkanol such as methanol or ethanol.
- the ammonia is then removed and the excess of alkali metal is destroyed by the addition of an alkanol.
- the resulting enolic ether is then hydrolyzed by the action of a strong mineral acid.
- the invention also relates to a process which leads to the compounds of general formula I using as starting materials an enol ether of 3,20-dioxo 19-nor pregna 4-ene, obtained from 3,20-dioxo 19-nor pregna 4-ene, raw materials, which have the following general formula IV:
- the compounds of general formula IV are etherified to enol ether with an alkyl orthoformate to obtain a compound of formula V
- R 2 is a lower alkyl radical
- R ', R "and R 1 are defined as above
- the invention also extends to aix pharmaceutical compositions containing, as active principle, at least one compound of general formula I alone, in mixture with one or more excipients or an inert, non-toxic, pharmaceutically acceptable vehicle.
- the invention also includes pharmaceutical compositions further comprising another active principle of similar action or synergistic or complementary.
- compositions according to the invention are intended for administration by parenteral, oral, rectal, per mucosa or per cutaneous route.
- the compounds of general formula I are administered in the form of solutions or injectable suspensions packaged in ampoules, multidose vials or self-injecting syringes.
- the compounds of general formula I are administered in the form of bare or coated tablets, dragees, capsules, soft capsules, pills, powders or granules.
- the compounds of general formula I are presented in the form of suppositories or rectal capsules.
- the compounds of general formula I are presented in the form of oily solutions, creams, jellies or capsules.
- the compounds of general formula I can be administered either through the vaginal mucosa, through the nasal mucosa in the form of a spray or gel, or through the ocular mucosa.
- the compounds of general formula I are presented in the form of a solution or of creams in a penetrating solvent such as benzyl alcohol, dimethylsulfojgrde, 1-n dodecyl azacycloheptanone-2 (AZONE (R) ) or N- ⁇ hydroxyethyl acetamide.
- a penetrating solvent such as benzyl alcohol, dimethylsulfojgrde, 1-n dodecyl azacycloheptanone-2 (AZONE (R) ) or N- ⁇ hydroxyethyl acetamide.
- compositions according to the invention find use in therapy for the treatment of gynecological disorders due to luteal insufficiency such as menstrual irregularity, dysmenorrhea, premenstrual syndrome and menopausal disorders. They can be used alone or in combination with estrogen as a contraceptive agent.
- the usual dosage ranges from 0.05 mg to 25 mg and the daily dosage ranges from 0.1 mg to 50 mg for continuous or periodic administration.
- the invention also extends to new intermediate products formed during the synthesis, namely:
- R ', R "and R 1 are defined as above, excluding the case where R' is methyl or ethyl, R 'and R" is hydrogen
- R 2 is a lower alkyl radical
- R 'and R " identical or different, represent hydrogen or a lower alkyl radical, having 1 to 3 carbon atoms, in a straight or branched chain
- R 1 represents a lower alkyl radical, identical or different from R 'or R ", having from 1 to 6 carbon atoms in a straight or branched chain.
- R 'and R " identical or different, represent hydrogen or a lower alkyl radical, having from 1 to 3 carbon atoms, in straight or branched chain
- Stage B 17 ⁇ -methyl 3,20-dioxo 19-nor pregna 4-ene and 17 ⁇ , 21- dimethyl 3,20-dioxo 19-nor pregna 4-ene
- a solution of 46 g of calcium in 1,000 ml of liquid ammonia cooled to -60 ° C. is prepared in advance and under an inert atmosphere, a solution of 30 g of enol ether of Stage A is added in a thin stream. in 495 ml of tetrahydrofuran. After 15 minutes of stirring, 363 ml of methyl iodide are added dropwise. a white-gray precipitate is formed. The end of the addition is followed by 60 min of stirring and then evaporation of the maximum possible ammonia under vacuum and under hot water bath. 1,000 ml of methanol and 6N hydrochloric acid are then added until the pH is acidic, while maintaining the temperature of the medium at 0 ° C. by immersion in an acetone / ice bath.
- This compound is prepared according to the same procedure as in Stage A, starting from 3,20-dioxo 17 ⁇ -methyl 19-nor pregna 4-ene, 12 ml of ethanol 1.85 ml of ethyl orthoformate, 0.102 g of p.toluene sulfonic acid and then 0.2 ml of triethylamine. Obtained with 78% yield, the crystalline enolic ether having the following physical constants:
- Stage D 3-ethoxy 6-formyl 17 ⁇ -methyl 20-oxo 19-nor pregna
- a formylation reagent is prepared by dissolving dropwise under nitrogen and at 2 °, 3.15 ml of POCl 3 freshly distilled in 28 ml of dimethylformamide followed by a stirring period of 5 min.
- the reagent thus prepared is added dropwise to a solution of 7 g of 3-ethoxy 17 ⁇ -methyl 20-oxo 19-nor pregna 3,5-diene in 56 ml of dimethylformamide in 10 to 15 minutes.
- NMR spectrum appearance of two singlets not very well resolved at 5 ppm and 5.25 ppm.
- a suspension of 0.65 g of 5% palladium on charcoal is prepared in 33.5 ml of methanol which is brought to reflux for 30 min. 1.34 g of 6-methylene derivative of Stage E is added. Heating is maintained at reflux. The reaction is monitored by determining the UV absorption. After 30 minutes of stirring, the mixture is allowed to return to room temperature. We filter it on Clarcel. The filtrate is concentrated, chromatographed on 30 times its weight of silica and eluted with Toluene. The fractions containing the 6-methyl derivative are recrystallized from methanol and thus 0.83 g of 3.20-dioxo 6.17 ⁇ -dimethyl 19-nor pregna 4,6-diene is obtained, ie 62% of theory.
- Stage B 3-ethoxy 6-formyl 17 ⁇ , 21-dimethyl 20-oxo 19-nor pregna
- Formulation in 6 of the compound of Stage A is carried out according to the procedure described in Stage D of Example I. Starting from 5.1 g of enolic ether of Stage A in 41 ml of dimethyl formamide.
- the formylation reagent consists of 2.15 ml of POCl, in 20 ml of dimethyl formamide.
- the hydrolysis reagent consists of 13.8 g of potassium acetate in 20 ml of water.
- 1 g of calcium is dissolved in 40 ml of liquid ammonia at -60 ° C and under an inert gas atmosphere.
- a solution of 1 g of 3-ethoxy 20-oxo 19-nor pregna diene 3.5 is then added, in a thin stream, in 18 ml of carefully dehydrated tetrahydrofuran. Stirring is continued for 1 hour and then 9.8 ml of ethyl iodide are added. The mixture is stirred for one hour and then the ammonia is evaporated in vacuo in a warm water bath.
- a whitish paste is collected which is diluted in 100 ml of methanol and then a 3N solution of hydrochloric acid is added to acid pH while cooling with an acetone / ice bath.
- the product is purified by chromatography, on 50 times its weight of silica, using 10% ether cyclohexane as solvent.
- the fraction corresponding to the 17 ⁇ -ethyl derivative is brought to dryness and the dry residue is recrystallized from cyclohexane.
- Stage B 3-ethoxy 17 ⁇ -ethyl 20-oxo 19-nor pregna 3,5-diene
- Ether-enolization is carried out according to the same procedure as that described in Stage A of Example 1 starting from 9.6 g of 17 ⁇ -ethyl derivative of Stage A in 29 ml of ethanol, with 9.6 ml of ethyl orthoformate and 0.048 g of p.toluene sulfonic acid then 1 ml of triethylamine.
- Stage C 3-ethoxy 6-formyl 17 ⁇ -ethyl 20-oxo 19-nor pregna
- the 6-methylene derivative is prepared from the 6-formylated derivative in Stage C, according to the same procedure as in Example I, Stage E starting from 0.5 g of 3-ethoxy 6-formyl 17 ⁇ -ethyl 20-oxo 19-nor pregna 3,5-diene in 65 ml of ethanol and 0.419 g of sodium borohydride then hydrolysis and dehydration with 8 ml of 2N sulfuric acid and 55 ml of water. 4.4 g of crude 6-methylen derivative are thus isolated, ie a yield of 76%. This product contains small amounts of the intermediate 6-hydroxy methyl derivative.
- a suspension formed of 5.5 g of palladium charcoal in 820 ml of ethanol is brought to reflux for 60 min.
- 4.1 g of 3.20-dioxo 6-methylene 17 ⁇ -ethyl 19-nor pregna 4-ene is added and the progress of the isomerization is monitored by UV spectrophotometry. After 8 min, the maximum has switched to 288 nm.
- the reaction is then stopped, the suspension is filtered on clarcel and the filtrate is brought to dryness. 3.65 g of crude 6-methylated product are collected.
- Stage B 3-methoxy 17 ⁇ -ethyl 20-oxo 19-nor pregna 1,3,5 (10) triene
- a solution of 3.75 g of lithium is prepared in 800 ml of liquid ammonia under argon and at -60 ° C. Then adding a solution of 50 g of 3-methoxy 17 ⁇ -acetyl 17 ⁇ -acetoxy estra 1,3,5 (10) Triene in 750 ml of Tetrahydrofuran. After 3 hours of stirring, 270 ml of ethyl iodide are added over 20 minutes and the mixture is stirred for 2 hours.
- Stage E 3-ethoxy 17 ⁇ -ethyl 21-methyl 20-oxo 19-nor pregna
- Stage F 3-ethoxy 6-formyl 17 ⁇ -ethyl 21-methyl 20-oxo 19-nor pregna 3,5-diene
- Progesterone labeled with Carbon C 14 is incubated with the uterine cytosol, alone or in the presence of increasing concentrations of cold steroid (including unlabeled progesterone), in an R ratio varying from 1 to 1000 between the two substances.
- the following table shows the percentages of labeled progesterone still bound to the receptor in the presence of the cold competitor.
- Compound D is 17 ⁇ -acetoxy 6.21 dimethyl 3-oxo 19-nor pregna
- Compound A is 3,20-dioxo 6,17 ⁇ -dimethyl 19-nor pregna
- Compound B is 3,20-dioxo 6-methyl 17 ⁇ -ethyl 19-nor pregna
- Compound C is 3,20-dioxo 6,17 ⁇ -20-trimethyl 19-nor pregna
- Relative affinity is the ratio between the 50% inhibition concentrations (C150) of a given steroid and the specific cold hormone taken for reference (here progesterone):
- This relative affinity is thus expressed as a percentage, considering that for the reference hormone (or steroid), the AR is equal to 100%.
- the C150s constitute an estimate of the Kl (inhibition constant) of the steroids tested for the binding of the reference steroid.
- the six products studied belong to a series of derivatives of nomegestrol acetate.
- the 17 ⁇ -methyl (Compound A), 17 ⁇ -ethyl (Compound B) and 17 ⁇ -acetoxy groups as in nomegestrol acetate give molecules whose affinity for the progestogen receptor is at least equal to that of progesterone and equivalent to that of Medroxyprogesterone.
- nomégestrol has the same side chain in 17 ⁇ as the three products tested (compound A, compound B and Nomégestrol acetate) but having a hydr ⁇ xyl in 17 ⁇ - shows a reduced affinity, from 40 to 60 times weaker than the three products cited above.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Steroid Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR8904910 | 1989-04-13 | ||
FR8904910A FR2645864B1 (fr) | 1989-04-13 | 1989-04-13 | Nouveaux derives alcoyles en 17/21 de la 19-nor progesterone, leurs procedes d'obtention et les compositions pharmaceutiques en renfermant |
Publications (1)
Publication Number | Publication Date |
---|---|
EP0437552A1 true EP0437552A1 (fr) | 1991-07-24 |
Family
ID=9380699
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP90907142A Withdrawn EP0437552A1 (fr) | 1989-04-13 | 1990-04-13 | Derives alcoyles en 17/21 de la 19-nor progesterone |
Country Status (12)
Country | Link |
---|---|
EP (1) | EP0437552A1 (ja) |
JP (1) | JPH04500523A (ja) |
KR (1) | KR920700219A (ja) |
AU (1) | AU635739B2 (ja) |
FI (1) | FI906116A0 (ja) |
FR (1) | FR2645864B1 (ja) |
HU (1) | HU208152B (ja) |
NO (1) | NO174393C (ja) |
OA (1) | OA09632A (ja) |
RU (1) | RU1836379C (ja) |
TN (1) | TNSN90053A1 (ja) |
WO (1) | WO1990012027A1 (ja) |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2675047B1 (fr) * | 1991-04-09 | 1995-05-12 | Theramex | Nouvelles compositions pharmaceutiques anti-glaucomateuses et leur procede d'obtention. |
ATE185071T1 (de) * | 1991-06-18 | 1999-10-15 | Theramex | Steroide enthaltende zusammensetzungen zur anwendung am auge und ihre verwendung zur behandlung des glaukoms |
FR2679236B1 (fr) * | 1991-07-18 | 1997-01-24 | Theramex | Nouveaux sterouides substitues en position 6, leurs procedes d'obtention et des compositions pharmaceutiques en renfermant. |
HU231125B1 (hu) * | 2016-12-16 | 2020-12-28 | Richter Gedeon Nyrt. | Ipari eljárás Nomegesztrol-acetát előállítására |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3361744A (en) * | 1962-07-18 | 1968-01-02 | American Cyanamid Co | Novel 17-hydrocarbon substituted progesterones, intermediates and methods of preparing the same |
FR2077877B1 (ja) * | 1970-02-20 | 1974-02-01 | Roussel Uclaf | |
FR2552766B1 (fr) * | 1983-10-04 | 1987-06-26 | Theramex | Nouveau procede de preparation de derives de la serie du 17 a-hydroxy 19-nor progesterone |
AU624096B2 (en) * | 1987-10-27 | 1992-06-04 | Laboratoire Theramex S.A. | Derivatives of 19-norprogesterone, their preparation and their use |
-
1989
- 1989-04-13 FR FR8904910A patent/FR2645864B1/fr not_active Expired - Fee Related
-
1990
- 1990-04-13 KR KR1019900702623A patent/KR920700219A/ko not_active Application Discontinuation
- 1990-04-13 WO PCT/FR1990/000270 patent/WO1990012027A1/fr not_active Application Discontinuation
- 1990-04-13 JP JP2506960A patent/JPH04500523A/ja active Pending
- 1990-04-13 EP EP90907142A patent/EP0437552A1/fr not_active Withdrawn
- 1990-04-13 TN TNTNSN90053A patent/TNSN90053A1/fr unknown
- 1990-04-13 AU AU55525/90A patent/AU635739B2/en not_active Ceased
- 1990-04-13 HU HU904373A patent/HU208152B/hu not_active IP Right Cessation
- 1990-12-11 NO NO905344A patent/NO174393C/no unknown
- 1990-12-12 FI FI906116A patent/FI906116A0/fi not_active Application Discontinuation
- 1990-12-12 RU SU904894526A patent/RU1836379C/ru active
- 1990-12-13 OA OA59916A patent/OA09632A/fr unknown
Non-Patent Citations (1)
Title |
---|
See references of WO9012027A1 * |
Also Published As
Publication number | Publication date |
---|---|
NO905344L (no) | 1991-02-01 |
HU208152B (en) | 1993-08-30 |
FR2645864B1 (fr) | 1991-07-12 |
FR2645864A1 (fr) | 1990-10-19 |
AU635739B2 (en) | 1993-04-01 |
WO1990012027A1 (fr) | 1990-10-18 |
OA09632A (fr) | 1993-04-30 |
AU5552590A (en) | 1990-11-05 |
FI906116A0 (fi) | 1990-12-12 |
NO905344D0 (no) | 1990-12-11 |
RU1836379C (ru) | 1993-08-23 |
TNSN90053A1 (fr) | 1991-03-05 |
JPH04500523A (ja) | 1992-01-30 |
KR920700219A (ko) | 1992-02-19 |
HUT56579A (en) | 1991-09-30 |
HU904373D0 (en) | 1991-06-28 |
NO174393B (no) | 1994-01-17 |
NO174393C (no) | 1994-04-27 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CA1266466A (fr) | Procede de preparation de steroides substitues en position 10 | |
EP0280618B1 (fr) | Nouveaux 19-nor stéroîdes substitués en position 7, leur préparation, leur application comme médicaments, les compositions pharmaceutiques les renfermant | |
EP0384842B1 (fr) | Nouveaux 19-nor stéroides ayant en position 11béta une chaîne carbonée comportant une fonction amide ou carbamate, leur procédé de préparation et les intermédiaires de ce procédé, leur application comme médicaments et les compositions pharmaceutiques les renfermant | |
EP0007823B1 (fr) | Nouveaux dérivés 3,20-dioxo 4,9-diène 21-hydroxyle stéroides, leur procédé de préparation, leur application à titre de médicaments et les compositions pharmaceutiques les renfermant | |
CA1260459A (fr) | Procede de preparation de nouveaux steroides substitues en position 10 par un radical comportant une double ou une triple liaison | |
EP0414606B1 (fr) | Nouveaux acides oméga-phénylamino alcanoiques substitués sur le noyau aromatique par un radical dérivé de 19-nor stéroides, leurs sels, leur procédé de préparation et les intermédiaires de ce procédé, leur application à titre de médicaments et les compositions les renfermant | |
WO1990012027A1 (fr) | Derives alcoyles en 17/21 de la 19-nor progesterone | |
EP0443957B1 (fr) | Nouveaux produits stéroides comportant un radical spiro en position 17, leur procédé de préparation et les intermédiaires de ce procédé, leur application à titre de médicaments et les compositions pharmaceutiques les renfermant | |
CA1231939A (fr) | PROCEDE DE PREPARATION DE DERIVES DE LA SERIE DE LA 17.alpha.-HYDROXY 19-NOR-PROGESTERONE | |
EP0338065B1 (fr) | Derives de la 19-nor progesterone, leur preparation et leur utilisation | |
EP0001029A1 (fr) | Procédé de préparation d'oximes en 3 de stéroides | |
EP0044575B1 (fr) | Produits intermédiaires dans la synthèse de 19-nor stéroides substitués en position 2 | |
EP0055170B1 (fr) | Nouveaux dérivés stéroides 3-céto delta 4 ou delta 1-4 substitués en position 7, leur préparation, leur application comme médicaments et les compositions les renfermant | |
CA1096372A (fr) | Procede de preparation de nouveaux 2,2-dimethyl 19- nor steroides | |
LU81497A1 (fr) | Nouveaux derives acetyleniques de l'androst-4-ene,leur procede de preparation,leur application comme medicament et les compositions pharmaceutiques les renfermant | |
EP0059146B1 (fr) | Nouveaux médicaments dérivés de la 3-hydroxy dodécahydro benz (e) inden-7-one, produits dérivés de la 3-hydroxy dodécahydro benz (e) inden-7-one et leur procédé de préparation | |
CA1122590A (fr) | Steroides, leur procede de preparation et leur application dans la synthese de steroides marques au tritium | |
WO1993002095A1 (fr) | Nouveaux steroides substitues en position 6 leurs procedes d'obtention et des compositions pharmaceutiques en renfermant | |
CH498867A (fr) | Procédé de préparation de dérivés stéroïdes insaturés substitués par un atome d'oxygène endocyclique |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AT BE CH DE DK ES FR GB IT LI LU NL SE |
|
17P | Request for examination filed |
Effective date: 19910529 |
|
17Q | First examination report despatched |
Effective date: 19931227 |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN |
|
18D | Application deemed to be withdrawn |
Effective date: 19940708 |