WO1994018224A1 - Steroides pour le traitement d'affections menopausiques - Google Patents
Steroides pour le traitement d'affections menopausiques Download PDFInfo
- Publication number
- WO1994018224A1 WO1994018224A1 PCT/EP1994/000348 EP9400348W WO9418224A1 WO 1994018224 A1 WO1994018224 A1 WO 1994018224A1 EP 9400348 W EP9400348 W EP 9400348W WO 9418224 A1 WO9418224 A1 WO 9418224A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- hydroxy
- optionally
- alkyl
- alkynyl
- halogen
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
-
- 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
- A61P15/12—Drugs for genital or sexual disorders; Contraceptives for climacteric disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- 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
- A61P5/30—Oestrogens
-
- 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
- C07J1/0088—Substituted in position 17 alfa and 17 beta the substituent in position 17 alfa being an unsaturated hydrocarbon group
- C07J1/0096—Alkynyl derivatives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J11/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J21/00—Normal steroids containing carbon, hydrogen, halogen or oxygen having an oxygen-containing hetero ring spiro-condensed with the cyclopenta(a)hydrophenanthrene skeleton
- C07J21/005—Ketals
- C07J21/008—Ketals at position 17
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J33/00—Normal steroids having a sulfur-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton
- C07J33/005—Normal steroids having a sulfur-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton spiro-condensed
- C07J33/007—Cyclic thioketals
-
- 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
- C07J41/0044—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 with an estrane or gonane skeleton, including 18-substituted derivatives and derivatives where position 17-beta is substituted by a carbon atom not directly bonded to another carbon atom and not being part of an amide group
-
- 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
- C07J41/0094—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 containing nitrile radicals, including thiocyanide radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J51/00—Normal steroids with unmodified cyclopenta(a)hydrophenanthrene skeleton not provided for in groups C07J1/00 - C07J43/00
Definitions
- the invention relates to the use of steroids for the manufacture of a medicament for treating or preventing menopausal complaints, especially for treating or preventing osteoporosis.
- ll ⁇ -alkyl steroid are known from USP 3,983,144. These steroids are described to have
- R-L represents 0, (H,OH), or two hydrogens atoms;
- R 2 is hydroxy, optionally etherified or esterified;
- R 3 is (2-6 C) alkynyl, optionally substituted with hydroxy;
- R is CN or one of the hydrocarbon groups selected from (1-6 C) alkyl, (1-6 C) alkoxy, (2-6 C) alkenyl, (2-6 C) alkynyl, and (2-6 C) alkylidene, each of said hydro ⁇ carbon groups may optionally be substituted with halogen, hydroxy or (1-6 C) alkoxy; and
- R 5 is hydrogen or (1-6 C) alkyl, can be used for treating or preventing postmenopausal complaints, and especially osteoporosis.
- the aim of this invention is to provide a medicament which is able to prevent bone loss, and possibly to increase bone mass, and further to treat climacteric complaints.
- the active ingre ⁇ pros of these medicaments have strong estrogen and weak or non-existing androgenic activity.
- Preferred medicaments further have favourable bleeding properties , do not induce endometrium proliferation, and have a favourable HDL/LDL (high/low density lipid) ratio.
- the compounds have the general formula I wherein R-L represents 0 or two hydrogens atoms; R is hydroxy; R 3 is ethynyl; R 4 is selected from the group consisting of methyl, (2-6 C) alkynyl, (2-6 C) alkylidene, and one of (2-6 C) alkyl, (2-7 C) alkoxy- alkyl, (1-6 C) alkoxy, or (2-6 C) alkenyl, which may optionally be substituted with halogen; and R 5 is hydro- gen or (1-6 C) alkyl.
- R ⁇ is 0; R 2 is hydroxy; R 3 is ethyn- yl; R 4 is ethyl, 2-fluoroethyl, ethynyl, (2-6 C) alkenyl optionally substituted with fluorine, or (2-6 C) alkyli ⁇ dene optionally substituted with fluorine; and R 5 is hydrogen or methyl. In the preferred embodiment R 5 is hydrogen.
- steroids having the general formula I wherein: R- ⁇ is O; R 2 is hydroxy; R 3 is ethynyl; R 4 is ethyl or ethynyl; and R 5 is hydrogen.
- the invention further relates to new steroids having the general formula I wherein:
- R ⁇ represents 0
- R 2 is hydroxy, optionally etherified or esterified;
- R 3 is (2-6 C) alkynyl, optionally substituted with hydroxy;
- R 4 is CN, (2-6 C) alkyl optionally substituted with halogen, or (2-6 C) alkenyl substituted with halogen; and R 5 is hydrogen or (1-6 C) alkyl; or wherein
- R- L represents two hydrogens atoms
- R 2 is hydroxy, optionally etherified or esterified;
- R 3 is (2-6 C) alkynyl, optionally substituted with hydroxy;
- R 4 is CN or one of the hydrocarbon groups selected from (2-6 C) alkyl, (1-6 C) alkoxy, (2-6 C) alkenyl, (2-6 C) alkynyl, and (2-6 C) alkylidene, each of said hydro ⁇ carbon groups may optionally be substituted with halogen, hydroxy or (1-6 C) alkoxy; and R 5 is (1-6 C) alkyl.
- steroids of general formula I wherein R ⁇ is O; R 2 is hydroxy; R 3 is ethynyl; R 4 is 2-fluoroethyl or 2-fluoro- ethenyl; and R 5 is hydrogen are preferred steroids.
- Other preferred steroids are steroids of general formula I wherein R j represents two hydrogens atoms; R 2 is hydroxy; R 3 is ethynyl; R 4 is (2-6 C) alkyl, (2-6 C) alkylidene or (2-6 C) alkenyl, each of which groups may be substituted with fluorine; and R 5 is methyl.
- the OH group may be etherified or esterified.
- etherified means that the hydroxy group is etherified with a lower alkyl group, preferably having 1-6 carbon atoms, such as methyl, ethyl, propyl, sec-butyl and the like.
- esterified means that the hydroxy group is esterified with a lower alkanoyl group, preferably having 2-6 carbon atoms, like acetyl, propionyl, and the like. In principle any ester suffices as long as the ester group cleaves when the compound is administered in vivo .
- the (1-6 C) alkyl group in the definition of formula I is a branched or unbranched alkyl group having 1-6 carbon atoms, such as methyl, ethyl, propyl, butyl, tert-butyl, pentyl and hexyl.
- the alkyl group is methyl (especially for R 5 ) and ethyl (especially for R 4 ).
- the term (2-6 C) alkyl has the same meaning with the exception of methyl.
- the (2-6 C) alkenyl group is a branched or unbranched alkenyl group having 2-6 carbon atoms, like vinyl, 2- propenyl, and 1,3-butadienyl.
- the (2-6 C) alkynyl group is a branched or unbranched alkynyl group having 2-6 carbon atoms, like ethynyl, propynyl, butynyl, and the like.
- the (2-6 C) alkylidene group is a branched or unbranched alkylidene group having 2-6 ' carbon atoms, like ethylidene, propylidene, 2-methylpropylidene, and the like.
- halogen used in the definition of formula I means fluorine, chlorine, bromine or iodine. Fluorine is the preferred halogen.
- (1-6 C) alkoxy means an alkoxy group, the alkyl moiety of which is a (1-6 C) alkyl group as previously defined.
- (2-7 C) alkoxyalkyl means a (1-6 C) alkyl group as previously defined substituted by a (1-6 C) alkoxy group as previously defined, the total number of carbon atoms being between 2 and 7.
- the new compounds of this invention can be prepared by condensation of 11-keto steroids of the general formula:
- R- L represents 0
- R 2 is hydroxy, optionally etherified or esterified
- R 3 is (2-6 C) alkynyl, optionally substituted with hydroxy
- R 5 is hydrogen or (1-6 C) alkyl; or wherein
- R- L represents two hydrogens atoms
- R 2 is hydroxy, optionally etherified or esterified
- R 3 is (2-6 C) alkynyl, optionally substituted with hydroxy
- R 5 is (1-6 C) alkyl; the active groups of which are optionally protected, is condensed with a Wittig(-like) compound of the formula
- R 'R 4 "CH-W wherein R 4 R 4 // C forms the group R 4 which is the optionally halogen, hydroxy, or (1-6 C) alkoxy substituted (2-6 C) alkylidene group as previously defined, or R 4 "'Li, wherein R 4 '" is (2-6 C) alkyl or (2-6 C) alkenyl optionally substituted with halogen, hydroxy, or (1-6 C) alkoxy, in which reactive groups can be protected by protective groups which are known in the art (see for example T.W.
- W is a Wittig, Wittig-Horner or Peterson-like moiety, optionally followed by halogenation and dehydration or by hydration, after which the compound obtained is converted into a nitrile or condensed with a Wittig(*- like) compound of the formula R g W, wherein W has the previously given meaning and R 6 is independently hydrogen, halogen or (1-6 C) alkyl, followed by hydroboration, optionally followed by alkylation, halogenation, or halogenation and dehydrohalogenation, or (partial) hydrogenation, after which optionally present protective groups are removed.
- Suitable reagents are triphenylphosphoranes such as R 4 R 4 / CH-P(Hal)Ph 3 and the like, and suitable Peterson reagents are, for example, trimethylsilane reagents like R 4 'R ' , C(MgHal)Si(CH 3 ) 3 , wherein Hal denotes a halogen like chlorine or bromine.
- the steroids of the invention can be used to prevent and treat estrogen deficiency induced disorders such as menopausal complaints, as is demonstrated in the estrogen-induced bone loss assay.
- young mature female Wistar rats are ovariectomized and treated with the test compound for 1 month.
- blood is collected and in the lithium-heparin plasma the bone turnover parameter (osteocalcin) is determined according to the method of Verhaeghe et al., J. Endrocrinol. , 120 , 143-151.
- the right femur is dissected and the bone density of the distal part of the metaphyse is measured using an X-ray densitometric method.
- the bone density, in mm aluminum equivalent is expressed in a percentage relative to the intact control group which is 100 % by definition, and to the ovariectomized control group which is 0 % by definition.
- osteocalcin is defined as 100 % for the ovariectomized group and 0 % for the intact group. Active compounds inhibit the bone turnover, and thus have an osteocalcin value lower than 100 %. Table I gives the results of this assay.
- the compounds of the invention may be administered enterally or parenterally, and for humans preferably in a daily dosage of 0,001-10 mg per kg body weight.
- pharmaceutically suitable auxiliaries e.g. as described in the standard reference, Gennaro et al.. Remington's Pharmaceutical Sciences, (18th ed. , Mack Publishing Company, 1990, see especially Part 8: Pharmaceutical Preparations and Their Manufacture
- the compounds may be compressed into solid dosage units, such as pills, tablets, or be processed into capsules or suppositories.
- the compounds can also be applied as an injection preparation in the form of a solution, suspension, emulsion, or as a spray, e.g. a nasal spray.
- a spray e.g. a nasal spray.
- dosage units e.g. tablets
- conventional additives such as fillers, colorants, poly ⁇ meric binders and the like is contemplated.
- any pharmaceutically acceptable additive which does not interfere with the function of the active compounds can be used.
- Suitable carriers with which the compositions can be administered include lactose, starch, cellulose derivatives and the like, or mixtures thereof, used in suitable amounts.
- Rf 0.77 (toluene-ethyl acetate 9/1) .
- a mixture of 6.1 g of (7 ⁇ )-3,3-ethanedithio-17,17- ethylenedioxy-7-methyl-ll-methylene-estr-4-en, 90 ml of acetone, 50 ml of tetrahydrofuran and 3 ml of 6 N hydrochloric acid was stirred at ambient temperature. After 1 h the mixture was diluted by addition of 700 ml of 5% sodium carbonate and stirred for h. The precipitate was filtered and dried to provide 5.4 g of (7 ⁇ )-3,3-ethanedithio-7-methyl-ll-methylene-estr-4-en- 17-one.
- R f 0.74 (toluene-ethyl acetate 9/1).
- Acetylene gas was passed through a solution of 50 g of potassium tert-butoxide in 500 ml of dry tetrahydro ⁇ furan. After 2 h a solution of 30 g of (7 ⁇ )-3,3- ethanedithio-7-methyl-ll-methylene-estr-4-en-17-one in 400 ml of tetrahydrofuran was introduced dropwise at 0 °C. After stirring for an additional 1 h the mixture was poured into 7 1 of water and stirred for an additional h.
- Dehydration of the oxime was effected by reacting 0.8 g of (7 ⁇ ,ll ⁇ ,17 ⁇ )-3,3-ethanedithio-17-tetrahydropyranyl- oxy-7-methylestr-4-en-ll-carboxaldehyde oxime in 8 ml of acetic anhydride during 45 min. Concomitant replacement of the 17-tetrahydropyran ether by an acetate group was observed. The reaction mixture was poured into 50 ml of ice water and stirred for 30 min.
- Acetylene gas was passed through a solution of 10.5 g of potassium tert-butoxide in 60 ml of dry tetrahydrofuran for 1 h at 0 °C. Then a solution of 9.3 g of (7 ⁇ ,ll ⁇ )- 3,3-ethanedithio-17-oxo-7-methylestr-4-en-ll-carbo- nitrile in 100 ml of tetrahydrofuran were added drop- wise. After stirring for 1 h at 0-5 °C the mixture was poured into 500 ml of saturated ammonium chloride solution and the product was extracted with ethyl acetate.
- lithium diisopropylamide prepared from 250 mg of dii ⁇ opropylamine and 1.6 ml of a 1.6M butyl lithium-hexane ⁇ olution
- 3 ml of tetrahydrofuran wa ⁇ added a solution of 600 mg of difluoromethyldiphenyl- pho ⁇ phinoxide in 2 ml of tetrahydrofuran at -50 °C.
- Acetylene gas was bubbled into a solution of 0.48 g of potassium tert-butoxide in a mixture of 5 ml of tetrahydrofuran and 0.5 ml of t-butanol. After 15 min a solution of 250 mg of ll ⁇ -(2,2-difluoroethylene)-estr-4- en-3,17-dione in 3 ml of tetrahydrofuran was added and 15 min later the mixture was quenched with water and the product extracted with ethyl acetate.
- the organic material wa ⁇ purified by chromatography to provide 1.9 g of (ll ⁇ ,E,17 ⁇ )-ll-(2-chloroethenyl-17-hydroxy-19-norpregn- 4-en-20-yn-3-one; M.p. 180 °C.
- Ba ⁇ e granule ⁇ were prepared by mixing the lactose with a portion of starch. The remainder of the starch wa ⁇ mixed to a slurry with water and added to the mixture. The whole was granulated and dried. The ⁇ e ba ⁇ e granule ⁇ were mixed with ascorbyl palmitate and the active ingredient, sieved, finely mixed with magnesium ⁇ tearate and then tabletted.
- Example 9 The components were mixed with one another in the manner described in Example 9, granulated and filled into gelatin cap ⁇ ule ⁇ .
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- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
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- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Epidemiology (AREA)
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Abstract
Priority Applications (9)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU60394/94A AU682170C (en) | 1993-02-08 | 1994-02-04 | Steroids for treating menopausal complaints |
BR9405825A BR9405825A (pt) | 1993-02-08 | 1994-02-04 | Uso de um esteróide esteróide processo para a preparação do mesmo e composição farmacéutica |
RU95118286/04A RU2172740C2 (ru) | 1993-02-08 | 1994-02-04 | Активный компонент лекарственного препарата, стероид, способ его получения и фармацевтическая композиция |
PL94310125A PL182901B1 (pl) | 1993-02-08 | 1994-02-04 | Steroidy do leczenia lub zapobiegania dolegliwościom menopauzalnym i środki farmaceutyczne zawierające steroidy |
HU9501940A HU220615B1 (hu) | 1993-02-08 | 1994-02-04 | Menopauzális panaszok kezelésére alkalmas szteroidok és azokat tartalmazó gyógyszerkészítmények |
JP6517652A JPH08506116A (ja) | 1993-02-08 | 1994-02-04 | 閉経期愁訴の治療用ステロイド |
EP94906918A EP0682672A1 (fr) | 1993-02-08 | 1994-02-04 | Steroides pour le traitement d'affections menopausiques |
FI953747A FI114101B (fi) | 1993-02-08 | 1995-08-07 | Menetelmä vaihdevuosivaivojen hoitoon käyttökelpoisten steroidien valmistamiseksi |
NO953089A NO308583B1 (no) | 1993-02-08 | 1995-08-07 | Anvendelse av steroider for fremstilling av et medikament for behandling av forstyrrelser indusert av østrogenmangel, steroidene samt farmasøytisk blanding |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP93200332 | 1993-02-08 | ||
EP93200332.0 | 1993-02-08 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US08/791,084 Continuation US5710144A (en) | 1993-02-08 | 1997-01-29 | C-11 substituted steroids for treating menopausal complaints |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1994018224A1 true WO1994018224A1 (fr) | 1994-08-18 |
Family
ID=8213615
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP1994/000348 WO1994018224A1 (fr) | 1993-02-08 | 1994-02-04 | Steroides pour le traitement d'affections menopausiques |
Country Status (15)
Country | Link |
---|---|
EP (1) | EP0682672A1 (fr) |
JP (1) | JPH08506116A (fr) |
KR (1) | KR100364113B1 (fr) |
CN (1) | CN1046735C (fr) |
AU (1) | AU4675897A (fr) |
BR (1) | BR9405825A (fr) |
CA (1) | CA2155532A1 (fr) |
FI (1) | FI114101B (fr) |
HU (2) | HU0102320D0 (fr) |
NO (1) | NO308583B1 (fr) |
NZ (1) | NZ261581A (fr) |
PL (1) | PL182901B1 (fr) |
RU (1) | RU2172740C2 (fr) |
WO (1) | WO1994018224A1 (fr) |
ZA (1) | ZA94715B (fr) |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0869132A1 (fr) * | 1997-02-21 | 1998-10-07 | Akzo Nobel N.V. | Stéroides ayant activité contraceptif et antiostéoporotique |
WO1999045886A2 (fr) * | 1998-03-09 | 1999-09-16 | Akzo Nobel N.V. | Nouveau kit de contraception |
WO2001018027A1 (fr) * | 1999-09-06 | 2001-03-15 | Akzo Nobel N.V. | Steroides oestrogeniques non aromatiques possedant un substituant hydrocarbure en position 11 |
US7696190B2 (en) | 2000-07-28 | 2010-04-13 | N.V. Organon | 16Alpha-methyl or ethyl substituted estrogens |
US7838516B2 (en) | 2004-09-08 | 2010-11-23 | N.V. Organon | 15 β-substituted steroids having selective estrogenic activity |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ES2881336T3 (es) * | 2016-03-03 | 2021-11-29 | Crystal Pharma Sau | Procedimiento y nuevos productos intermedios para la preparación de 11-metilen-esteroides |
Citations (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3325520A (en) * | 1965-12-08 | 1967-06-13 | Searle & Co | (optionally 17-hydrocarbon-substituted) 11, 13beta-dialkylgon-4-en-3-ones and esters corresponding |
US3465010A (en) * | 1966-11-22 | 1969-09-02 | Searle & Co | 17 - (unsaturated hydrocarbon - substituted) 11,13beta - dialkylgon -4 - ene - 3,17beta-diols and esters thereof |
NL7216767A (fr) * | 1972-12-09 | 1974-06-11 | ||
US3983144A (en) * | 1973-12-19 | 1976-09-28 | Akzona Incorporated | Novel 11β-alkyl steroids of the estrane series |
NL7701384A (nl) * | 1977-02-10 | 1978-08-14 | Akzo Nv | Werkwijze voor het bereiden van nieuwe steroiden van de oestraanreeks. |
GB2058564A (en) * | 1979-09-07 | 1981-04-15 | Horton J E | Pharmaceutical compositions comprising anti-osteoporotic agents |
EP0136011A2 (fr) * | 1983-08-05 | 1985-04-03 | Pre Jay Holdings Ltd. | Méthode de traitement hormonal de troubles de la périménopause, ménopause et postménopause et emballage à préparations multiples dans ce but |
EP0145493A2 (fr) * | 1983-12-14 | 1985-06-19 | The Upjohn Company | 11-Difluorométhyl et 11-fluorométhylène stéroide |
NL8502571A (nl) * | 1985-09-20 | 1987-04-16 | Akzo Nv | Steroiden met immunomodulerende eigenschappen. |
DE3702383A1 (de) * | 1987-01-23 | 1988-08-04 | Schering Ag | 11ss-alkinylestrene und -estradiene, deren herstellung und diese enthaltende pharmazeutische praeparate |
EP0337938A2 (fr) * | 1988-03-14 | 1989-10-18 | Sandoz Ag | Dérivés de 19-norprogestérone dans le traitement de l'ostéoporose |
EP0461290A1 (fr) * | 1990-06-14 | 1991-12-18 | HENNING BERLIN GmbH CHEMIE- UND PHARMAWERK | Capsules à couleur liquide |
EP0474374A1 (fr) * | 1990-08-10 | 1992-03-11 | Ortho Pharmaceutical Corporation | Méthode de traitement des maladies avec atrophie osseuse utilisant une progestine |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FI54128C (fi) * | 1972-12-09 | 1978-10-10 | Akzo Nv | Foerfarande foer framstaellning av nya 11,11-alkylidensteroider ur oestran- och 19-norpregnanserien med foerbaettrad hormonell verkan |
-
1994
- 1994-02-02 ZA ZA94715A patent/ZA94715B/xx unknown
- 1994-02-04 CA CA002155532A patent/CA2155532A1/fr not_active Abandoned
- 1994-02-04 EP EP94906918A patent/EP0682672A1/fr not_active Withdrawn
- 1994-02-04 JP JP6517652A patent/JPH08506116A/ja active Pending
- 1994-02-04 KR KR1019950703263A patent/KR100364113B1/ko not_active IP Right Cessation
- 1994-02-04 PL PL94310125A patent/PL182901B1/pl not_active IP Right Cessation
- 1994-02-04 RU RU95118286/04A patent/RU2172740C2/ru not_active IP Right Cessation
- 1994-02-04 BR BR9405825A patent/BR9405825A/pt not_active Application Discontinuation
- 1994-02-04 HU HU0102320A patent/HU0102320D0/hu unknown
- 1994-02-04 CN CN94191126A patent/CN1046735C/zh not_active Expired - Fee Related
- 1994-02-04 HU HU9501940A patent/HU220615B1/hu not_active IP Right Cessation
- 1994-02-04 NZ NZ261581A patent/NZ261581A/en unknown
- 1994-02-04 WO PCT/EP1994/000348 patent/WO1994018224A1/fr not_active Application Discontinuation
-
1995
- 1995-08-07 NO NO953089A patent/NO308583B1/no unknown
- 1995-08-07 FI FI953747A patent/FI114101B/fi not_active IP Right Cessation
-
1997
- 1997-11-28 AU AU46758/97A patent/AU4675897A/en not_active Abandoned
Patent Citations (15)
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US3325520A (en) * | 1965-12-08 | 1967-06-13 | Searle & Co | (optionally 17-hydrocarbon-substituted) 11, 13beta-dialkylgon-4-en-3-ones and esters corresponding |
US3465010A (en) * | 1966-11-22 | 1969-09-02 | Searle & Co | 17 - (unsaturated hydrocarbon - substituted) 11,13beta - dialkylgon -4 - ene - 3,17beta-diols and esters thereof |
GB1190240A (en) * | 1966-11-22 | 1970-04-29 | Searle & Co | 07-(Unsaturated Hydrocarbon-Substituted) 11,13beta-Dialkylgon-4-Ene-3,17beta-Diols and Esters thereof |
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US3983144A (en) * | 1973-12-19 | 1976-09-28 | Akzona Incorporated | Novel 11β-alkyl steroids of the estrane series |
US4292251A (en) * | 1977-02-10 | 1981-09-29 | Akzona Incorporated | 11β-Substituted steroids |
NL7701384A (nl) * | 1977-02-10 | 1978-08-14 | Akzo Nv | Werkwijze voor het bereiden van nieuwe steroiden van de oestraanreeks. |
GB2058564A (en) * | 1979-09-07 | 1981-04-15 | Horton J E | Pharmaceutical compositions comprising anti-osteoporotic agents |
EP0136011A2 (fr) * | 1983-08-05 | 1985-04-03 | Pre Jay Holdings Ltd. | Méthode de traitement hormonal de troubles de la périménopause, ménopause et postménopause et emballage à préparations multiples dans ce but |
EP0145493A2 (fr) * | 1983-12-14 | 1985-06-19 | The Upjohn Company | 11-Difluorométhyl et 11-fluorométhylène stéroide |
NL8502571A (nl) * | 1985-09-20 | 1987-04-16 | Akzo Nv | Steroiden met immunomodulerende eigenschappen. |
DE3702383A1 (de) * | 1987-01-23 | 1988-08-04 | Schering Ag | 11ss-alkinylestrene und -estradiene, deren herstellung und diese enthaltende pharmazeutische praeparate |
EP0337938A2 (fr) * | 1988-03-14 | 1989-10-18 | Sandoz Ag | Dérivés de 19-norprogestérone dans le traitement de l'ostéoporose |
EP0461290A1 (fr) * | 1990-06-14 | 1991-12-18 | HENNING BERLIN GmbH CHEMIE- UND PHARMAWERK | Capsules à couleur liquide |
EP0474374A1 (fr) * | 1990-08-10 | 1992-03-11 | Ortho Pharmaceutical Corporation | Méthode de traitement des maladies avec atrophie osseuse utilisant une progestine |
Non-Patent Citations (4)
Title |
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A.J.VAN DEN BROEK ET AL.: "11-ALKYLIDENE STEROIDS IN THE 19-NOR SERIES", RECL.TRAV.CHIM.PAYS-BAS, vol. 94, no. 2, 1975, pages 35 - 39, XP009036160 * |
E.W.BERGINK ET AL.: "BINDING OF A CONTRACEPTIVE PROGESTOGEN ORG 2969 AND ITS METABOLITES TO RECEPTOR PROTEINS AND HUMAN SEX HORMONE BINDING GLOBULIN", J. STEROID BIOCHEM., vol. 14, no. 2, February 1981 (1981-02-01), pages 175 - 183, XP023415170, DOI: doi:10.1016/0022-4731(81)90171-0 * |
H.-O. HOPPEN ET AL.: "THE INFLUENCE OF STRUCTURAL MODIFICATION ON PROGESTERONE AND ANDROGEN RECEPTOR BINDING OF NORETHISTERONE. CORRELATION WITH NUCLEAR MAGNETIC RESONANCE SIGNALS", ACTA ENDOCRINOL., vol. 115, no. 3, July 1987 (1987-07-01), pages 406 - 412 * |
J.S.BARAN ET AL.: "11-BETA-METHYL-19-NORSTEROIDS: NOVEL PROGESTATIONAL HORMONES", EXPERIENTIA, vol. 26, no. 7, 1970, pages 762 - 763 * |
Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0869132A1 (fr) * | 1997-02-21 | 1998-10-07 | Akzo Nobel N.V. | Stéroides ayant activité contraceptif et antiostéoporotique |
US6077873A (en) * | 1997-02-21 | 2000-06-20 | Akzo Nobel N.V. | Steroid compounds having contraceptive and anti-osteoporosis activity |
WO1999045886A2 (fr) * | 1998-03-09 | 1999-09-16 | Akzo Nobel N.V. | Nouveau kit de contraception |
WO1999045886A3 (fr) * | 1998-03-09 | 1999-12-02 | Akzo Nobel Nv | Nouveau kit de contraception |
AU756882B2 (en) * | 1998-03-09 | 2003-01-23 | Akzo Nobel N.V. | New contraceptive kit |
WO2001018027A1 (fr) * | 1999-09-06 | 2001-03-15 | Akzo Nobel N.V. | Steroides oestrogeniques non aromatiques possedant un substituant hydrocarbure en position 11 |
US6677329B1 (en) | 1999-09-06 | 2004-01-13 | Akzo Nobel N V. | Non-aromatic estrogenic steroids with a hydrocarbon substituent in position 11 |
US7696190B2 (en) | 2000-07-28 | 2010-04-13 | N.V. Organon | 16Alpha-methyl or ethyl substituted estrogens |
US7838516B2 (en) | 2004-09-08 | 2010-11-23 | N.V. Organon | 15 β-substituted steroids having selective estrogenic activity |
Also Published As
Publication number | Publication date |
---|---|
AU682170B2 (en) | 1997-09-25 |
NO953089L (no) | 1995-10-06 |
AU6039494A (en) | 1994-08-29 |
ZA94715B (en) | 1994-10-24 |
CA2155532A1 (fr) | 1994-08-18 |
NO308583B1 (no) | 2000-10-02 |
JPH08506116A (ja) | 1996-07-02 |
RU2172740C2 (ru) | 2001-08-27 |
HUT72971A (en) | 1996-06-28 |
PL310125A1 (en) | 1995-11-27 |
CN1046735C (zh) | 1999-11-24 |
NZ261581A (en) | 1997-06-24 |
PL182901B1 (pl) | 2002-03-29 |
BR9405825A (pt) | 1995-12-05 |
CN1117735A (zh) | 1996-02-28 |
HU220615B1 (hu) | 2002-03-28 |
HU9501940D0 (en) | 1995-09-28 |
FI114101B (fi) | 2004-08-13 |
NO953089D0 (no) | 1995-08-07 |
HU0102320D0 (en) | 2001-08-28 |
EP0682672A1 (fr) | 1995-11-22 |
FI953747A0 (fi) | 1995-08-07 |
KR100364113B1 (ko) | 2003-04-08 |
FI953747A (fi) | 1995-09-12 |
AU4675897A (en) | 1998-02-19 |
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