HRP20161369T1 - Postupak za proizvodnju intermedijera estetrola - Google Patents
Postupak za proizvodnju intermedijera estetrola Download PDFInfo
- Publication number
- HRP20161369T1 HRP20161369T1 HRP20161369TT HRP20161369T HRP20161369T1 HR P20161369 T1 HRP20161369 T1 HR P20161369T1 HR P20161369T T HRP20161369T T HR P20161369TT HR P20161369 T HRP20161369 T HR P20161369T HR P20161369 T1 HRP20161369 T1 HR P20161369T1
- Authority
- HR
- Croatia
- Prior art keywords
- group
- compound
- formula
- process according
- sulfonation
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims 17
- AJIPIJNNOJSSQC-NYLIRDPKSA-N estetrol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H]([C@H](O)[C@@H]4O)O)[C@@H]4[C@@H]3CCC2=C1 AJIPIJNNOJSSQC-NYLIRDPKSA-N 0.000 title claims 3
- 229950009589 estetrol Drugs 0.000 title claims 3
- 238000004519 manufacturing process Methods 0.000 title claims 2
- 239000000543 intermediate Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims 13
- 238000006277 sulfonation reaction Methods 0.000 claims 7
- 239000003153 chemical reaction reagent Substances 0.000 claims 4
- 230000026030 halogenation Effects 0.000 claims 4
- 238000005658 halogenation reaction Methods 0.000 claims 4
- 125000001424 substituent group Chemical group 0.000 claims 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 3
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 claims 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims 3
- 238000006243 chemical reaction Methods 0.000 claims 3
- 239000003638 chemical reducing agent Substances 0.000 claims 3
- 239000003795 chemical substances by application Substances 0.000 claims 3
- 125000001153 fluoro group Chemical group F* 0.000 claims 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims 3
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 claims 2
- 125000000217 alkyl group Chemical group 0.000 claims 2
- 230000031709 bromination Effects 0.000 claims 2
- 238000005893 bromination reaction Methods 0.000 claims 2
- QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 claims 2
- 238000005695 dehalogenation reaction Methods 0.000 claims 2
- 230000006326 desulfonation Effects 0.000 claims 2
- 238000005869 desulfonation reaction Methods 0.000 claims 2
- 239000012279 sodium borohydride Substances 0.000 claims 2
- 229910000033 sodium borohydride Inorganic materials 0.000 claims 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 1
- XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 claims 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims 1
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims 1
- 229910004664 Cerium(III) chloride Inorganic materials 0.000 claims 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims 1
- 229910021590 Copper(II) bromide Inorganic materials 0.000 claims 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims 1
- 229910010084 LiAlH4 Inorganic materials 0.000 claims 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims 1
- 150000001263 acyl chlorides Chemical class 0.000 claims 1
- 150000008064 anhydrides Chemical class 0.000 claims 1
- HOPRXXXSABQWAV-UHFFFAOYSA-N anhydrous collidine Natural products CC1=CC=NC(C)=C1C HOPRXXXSABQWAV-UHFFFAOYSA-N 0.000 claims 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims 1
- UHNOAGDNODCLKN-UHFFFAOYSA-N bromine;pyridine Chemical compound [Br].C1=CC=NC=C1 UHNOAGDNODCLKN-UHFFFAOYSA-N 0.000 claims 1
- 229910052794 bromium Inorganic materials 0.000 claims 1
- VYLVYHXQOHJDJL-UHFFFAOYSA-K cerium trichloride Chemical compound Cl[Ce](Cl)Cl VYLVYHXQOHJDJL-UHFFFAOYSA-K 0.000 claims 1
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- NBWIIOQJUKRLKW-UHFFFAOYSA-N chloro(phenyl)silane Chemical compound Cl[SiH2]C1=CC=CC=C1 NBWIIOQJUKRLKW-UHFFFAOYSA-N 0.000 claims 1
- UTBIMNXEDGNJFE-UHFFFAOYSA-N collidine Natural products CC1=CC=C(C)C(C)=N1 UTBIMNXEDGNJFE-UHFFFAOYSA-N 0.000 claims 1
- 229910000365 copper sulfate Inorganic materials 0.000 claims 1
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 125000001072 heteroaryl group Chemical group 0.000 claims 1
- 239000012280 lithium aluminium hydride Substances 0.000 claims 1
- 229910052987 metal hydride Inorganic materials 0.000 claims 1
- -1 metal hydride compounds Chemical class 0.000 claims 1
- OMGWPAUMPKUGQL-UHFFFAOYSA-N methyl 4-chlorobenzenesulfinate Chemical compound COS(=O)C1=CC=C(Cl)C=C1 OMGWPAUMPKUGQL-UHFFFAOYSA-N 0.000 claims 1
- MGPLBSPZSIFUQX-LLVKDONJSA-N methyl 4-methylbenzenesulfinate Chemical compound CO[S@@](=O)C1=CC=C(C)C=C1 MGPLBSPZSIFUQX-LLVKDONJSA-N 0.000 claims 1
- PSNSVDSRLUYDKF-UHFFFAOYSA-N methyl benzenesulfinate Chemical compound COS(=O)C1=CC=CC=C1 PSNSVDSRLUYDKF-UHFFFAOYSA-N 0.000 claims 1
- CECDAUNJGIUIIW-UHFFFAOYSA-N methyl pyridine-2-sulfinate Chemical group COS(=O)C1=CC=CC=N1 CECDAUNJGIUIIW-UHFFFAOYSA-N 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- PZABZCASVQXUET-UHFFFAOYSA-N phenylsilyl trifluoromethanesulfonate Chemical compound FC(F)(F)S(=O)(=O)O[SiH2]C1=CC=CC=C1 PZABZCASVQXUET-UHFFFAOYSA-N 0.000 claims 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 claims 1
- 229910000105 potassium hydride Inorganic materials 0.000 claims 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims 1
- 125000006239 protecting group Chemical group 0.000 claims 1
- 229910052708 sodium Inorganic materials 0.000 claims 1
- 239000011734 sodium Substances 0.000 claims 1
- 229910000104 sodium hydride Inorganic materials 0.000 claims 1
- 239000012312 sodium hydride Substances 0.000 claims 1
- GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 claims 1
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
- C07J1/0003—Androstane derivatives
- C07J1/0018—Androstane derivatives substituted in position 17 beta, not substituted in position 17 alfa
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J75/00—Processes for the preparation of steroids in general
-
- 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
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- 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
- A61P15/02—Drugs for genital or sexual disorders; Contraceptives for disorders of the vagina
-
- 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
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/18—Feminine contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- 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
- C07J1/0059—Estrane derivatives substituted in position 17 by a keto group
-
- 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
- C07J1/0066—Estrane derivatives substituted in position 17 beta not substituted in position 17 alfa
- C07J1/007—Estrane derivatives substituted in position 17 beta not substituted in position 17 alfa the substituent being an OH group free esterified or etherified
-
- 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
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Dermatology (AREA)
- Gynecology & Obstetrics (AREA)
- Diabetes (AREA)
- Steroid Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Claims (14)
1. Postupak za pripravu spoja formule (I)
[image]
obuhvaća sljedeće korake
a) reakciju spoja formule (II) sa sililirajućim ili acilirajućim sredstvom kako bi se dobio spoj formule (III), gdje je P¹ neovisna zaštitna skupina odabrana iz R²-Si-R³R4, ili R¹CO-, pri čemu je R¹ skupina odabrana iz C1-6alkila ili C3-6cikloalkila, a svaka skupina po izboru je supstituirana sa jednim ili više supstituenata neovisno odabranih od fluoro ili C1-4alkila; svaka od R², R³ i R4 su neovisna skupina odabrana od C1-6alkila ili fenila, svaka skupina po izboru je supstituirana sa jednim ili više supstituenata neovisno odabranih od fluoro ili C1-4alkila;
[image]
b) halogeniranje ili sulfoniranje spoja formule (III) kako bi se dobio spoj formule (IV); pri čemu je X halo, ili -SO-R5, i R5 je skupina odabrana od C6-10arila ili heteroarila, svaka skupina po izboru je supstituirana sa jednim ili više supstituenata neovisno odabranih od kloro ili C1-4alkila;
[image]
c) dehalogeniranje ili desulfoniranje spoja formule (IV) kako bi se dobio spoj formule (V); i
[image]
d) reakciju spoja formule (V) sa redukcijskim sredstvom kako bi se dobio spoj formule (I), pri čemu je C6-10 aril namjenjen da uključuje također derivate djelomično hidrogenirane.
2. Postupak prema zahtjevu 1, u kome je korak (b) sulfoniranje a sulfoniranje se izvodi reakcijom spoja formule (III) sa bazom i reagensom za sulfoniranje.
3. Postupak prema zahtjevima 1 ili 2, u kome je korak (b) sulfoniranje a reagens za sulfoniranje je metil 2-piridinsulfinat, metil benzensulfinat, metil 4-metil-benzensulfinat, metil 4-kloro-benzen sulfinat.
4. Postupak prema zahtjevima 2 ili 3, u kome je baza korištena u koraku sulfoniranja odabrana iz skupine koja obuhvaća kalijev hidrid, kalijev terbutilat, natrijev hidrid, natrijev terbutilat i njihove smjese.
5. Postupak prema zahtjevu 9, u kome je korak (b) halogeniranje a halogeniranje se izvodi reakcijom spoja formule (III) sa reagensom za halogeniranje.
6. Postupak prema zahtjevima 1 ili 5, u kome je korak (b) bromiranje a reagens za bromiranje odabran je iz skupine koja obuhvaća bakar (II) bromid, brom, i piridin brom perbromin.
7. Postupak prema bilo kojem od zahtjeva 1 do 4, u kome se korak desulfoniranja provodi toplinom, poželjno u prisutnosti bakrenog sulfata.
8. Postupak prema bilo kojem od zahtjeva 1, 5-6, u kome se korak dehalogeniranja provodi u prisutnosti baze.
9. Postupak u skladu sa zahtjevom 8, u kome je baza odabrana iz skupine koja obuhvaća imidazol, kolidin, 2,6-lutidin, trietilamin, ili 1,8-diazabiciklo [5.4.0]undek-7-en.
10. Postupak prema bilo kojem od zahtjeva 1 do 9, u kome se korak (c) izvodi koristeći redukcijsko sredstvo odabrano iz skupine koja obuhvaća spojeve metalnih hidrida.
11. Postupak prema kojem od zahtjeva 1 do 10, u kome se korak (c) izvodi koristeći redukcijsko sredstvo odabrano iz skupine koja obuhvaća NaBH4/CeCl3, LiAlH4, NaBH4, NaBH(OAc)3 i ZnBH4.
12. Postupak prema bilo kojem od zahtjeva 1 do 11, u kome se sredstvo za sililiranje odabire iz skupine koja obuhvaća C1-6alkilsililklorid, C1-6alkilsililtriflat, fenilsililklorid, fenilsililtriflat, C1-6alkilfenilsililklorid, C1-6alkilfenilsililtriflat, svaka skupina poželjno je supstituirana sa jednim ili više supstituenata neovisno odabranih od fluoro ili C1-4alkila.
13. Postupak prema bilo kojem od zahtjeva 1 do 11, u kome se acilirajuće sredstvo odabire iz skupine koju čine C2-6alkenilC1-6alkanoat, C2-6alkenilC3-6cikloalkanoat, acil kloridi i anhidridi.
14. Postupak za pripravu estetrola, spomenuti postupak obuhvaća pripravu spoja formule (I) postupkom prema bilo kojem od zahtjeva 1 do 13, i daljnju reakciju spoja formule (I) za proizvodnju estetrola.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161492297P | 2011-06-01 | 2011-06-01 | |
| EP11168560 | 2011-06-01 | ||
| PCT/EP2012/060446 WO2012164095A1 (en) | 2011-06-01 | 2012-06-01 | Process for the production of estetrol intermediates |
| EP12729053.4A EP2714712B1 (en) | 2011-06-01 | 2012-06-01 | Process for the production of estetrol intermediates |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20161369T1 true HRP20161369T1 (hr) | 2016-12-02 |
Family
ID=44588329
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20161369TT HRP20161369T1 (hr) | 2011-06-01 | 2016-10-20 | Postupak za proizvodnju intermedijera estetrola |
Country Status (25)
| Country | Link |
|---|---|
| US (1) | US11053273B2 (hr) |
| EP (1) | EP2714712B1 (hr) |
| JP (1) | JP6116550B2 (hr) |
| KR (1) | KR101957937B1 (hr) |
| CN (1) | CN103619867B (hr) |
| AU (1) | AU2012264601C1 (hr) |
| BR (1) | BR112013030833B1 (hr) |
| CA (1) | CA2835979C (hr) |
| CY (1) | CY1118164T1 (hr) |
| DK (1) | DK2714712T3 (hr) |
| EA (1) | EA025511B1 (hr) |
| ES (1) | ES2600703T3 (hr) |
| HR (1) | HRP20161369T1 (hr) |
| HU (1) | HUE031809T2 (hr) |
| LT (1) | LT2714712T (hr) |
| ME (1) | ME02585B (hr) |
| MX (1) | MX342537B (hr) |
| PL (1) | PL2714712T3 (hr) |
| PT (1) | PT2714712T (hr) |
| RS (1) | RS55293B1 (hr) |
| SG (1) | SG195121A1 (hr) |
| SI (1) | SI2714712T1 (hr) |
| SM (1) | SMT201600408B (hr) |
| WO (1) | WO2012164095A1 (hr) |
| ZA (1) | ZA201308445B (hr) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2579175T3 (es) | 2011-06-01 | 2016-08-05 | Estetra S.P.R.L. | Proceso para la producción de intermediarios de estetrol |
| EA025511B1 (ru) | 2011-06-01 | 2016-12-30 | Эстетра С.П.Р.Л. | Способ получения промежуточных соединений эстетрола |
| EP2383279A1 (en) | 2011-07-19 | 2011-11-02 | Pantarhei Bioscience B.V. | Process for the preparation of estetrol |
| EP2764008B1 (en) | 2011-10-07 | 2016-08-17 | Estetra S.P.R.L. | Process for the production of estetrol |
| SI3701944T1 (sl) | 2015-06-18 | 2022-04-29 | Estetra Srl | Orodisperzibilna odmerna enota, ki vsebuje estetrolno komponento |
| CN107771075A (zh) | 2015-06-18 | 2018-03-06 | 密特拉制药公司 | 含雌四醇组分的口腔分散剂量单位 |
| MD3310345T2 (ro) | 2015-06-18 | 2021-07-31 | Estetra Sprl | Comprimată orodispersabilă ce conține estetrol |
| CN107750157B (zh) | 2015-06-18 | 2021-07-13 | 埃斯特拉私人有限责任公司 | 含雌四醇的口腔分散片剂 |
| KR20220144885A (ko) | 2016-08-05 | 2022-10-27 | 에스테트라, 소시에떼 아 레스폰서빌리떼 리미떼 | 월경통 및 생리통의 관리방법 |
| TWI801561B (zh) | 2018-04-19 | 2023-05-11 | 比利時商依思特拉私人有限責任公司 | 化合物及其用於緩解絕經相關症狀的用途 |
| JOP20200260A1 (ar) | 2018-04-19 | 2019-10-19 | Estetra Sprl | مركبات واستخداماتها للتخفيف من الأعراض المصاحبة لانقطاع الطمث |
| WO2023021026A1 (en) | 2021-08-17 | 2023-02-23 | Aspen Oss B.V. | A synthetic pathway to estra-1,3,5(10)-triene-3,15a,16a,17b-tetrol |
Family Cites Families (71)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE144266C (hr) | ||||
| US3138588A (en) | 1962-08-24 | 1964-06-23 | American Home Prod | 17-ketals of estrone and derivatives thereof |
| US3177206A (en) | 1963-03-07 | 1965-04-06 | American Home Prod | Selective bromination of a-ring aromatic 17-ketalized steroids |
| US3433785A (en) | 1966-07-11 | 1969-03-18 | Sterling Drug Inc | 15,16-disubstituted aromatic steroids,intermediates and processes |
| US3673180A (en) | 1970-06-18 | 1972-06-27 | Merck & Co Inc | 19-nor-6,6-ethylene-20-spiroxenes |
| US4792620A (en) | 1983-10-14 | 1988-12-20 | Bp Chemicals Limited | Carbonylation catalysts |
| US4739078A (en) | 1984-02-17 | 1988-04-19 | The Upjohn Company | Use of borohydride-salt lanthanide salt reagents for stereo selective reduction of C-15-keto prostaglandin precursors |
| IE60780B1 (en) | 1987-01-23 | 1994-08-10 | Akzo Nv | New 11-aryl steroid derivatives |
| DE3710728A1 (de) | 1987-03-31 | 1988-10-13 | Schering Ag | Verfahren zur herstellung von 17(alpha)-ethinyl-17ss-hydroxy-18-methyl-4,15-estradien-3-on und die neuen zwischenprodukte fuer dieses verfahren |
| US5073374A (en) | 1988-11-30 | 1991-12-17 | Schering Corporation | Fast dissolving buccal tablet |
| US5340586A (en) | 1991-04-12 | 1994-08-23 | University Of Southern California | Methods and formulations for use in treating oophorectomized women |
| JPH07101977A (ja) | 1993-10-05 | 1995-04-18 | Kureha Chem Ind Co Ltd | ホルモン作用を軽減した新規なエストラジオール誘導体及びその増殖因子阻害剤 |
| WO1997004752A1 (en) | 1995-07-26 | 1997-02-13 | Duramed Pharmaceuticals, Inc. | Pharmaceutical compositions of conjugated estrogens and methods for their use |
| US6117446A (en) | 1999-01-26 | 2000-09-12 | Place; Virgil A. | Drug dosage unit for buccal administration of steroidal active agents |
| TW548277B (en) * | 1999-07-16 | 2003-08-21 | Akzo Nobel Nv | Orally active androgens |
| US20020132801A1 (en) | 2001-01-11 | 2002-09-19 | Schering Aktiengesellschaft | Drospirenone for hormone replacement therapy |
| EP1260225A1 (en) | 2001-05-18 | 2002-11-27 | Pantarhei Bioscience B.V. | A pharmaceutical composition for use in hormone replacement therapy |
| ATE350041T1 (de) | 2001-05-18 | 2007-01-15 | Pantarhei Bioscience Bv | Pharmaceutishe zusammensetzung für die hormonersatztherapie |
| US7871995B2 (en) | 2001-05-23 | 2011-01-18 | Pantarhei Bioscience B.V. | Drug delivery system comprising a tetrahydroxylated estrogen for use in hormonal contraception |
| DK1390042T3 (da) | 2001-05-23 | 2008-03-31 | Pantarhei Bioscience Bv | System for administration af et lægemiddel omfattende tetrahydroxyleret östrogen til anvendelse i hormonal svangerskabsforebyggelse |
| WO2003018026A1 (en) | 2001-08-31 | 2003-03-06 | Pantarhei Bioscience B.V. | Use of estrogenic compounds in combination with progestogenic compounds in hormone-replacement therapy |
| ES2278925T3 (es) | 2001-11-15 | 2007-08-16 | Pantarhei Bioscience B.V. | Uso de compuestos estrogenicos en combinacion con compuestos progestogenicos en terapias de sustitucion hormonal. |
| US6723348B2 (en) | 2001-11-16 | 2004-04-20 | Ethypharm | Orodispersible tablets containing fexofenadine |
| HU227198B1 (en) | 2001-11-27 | 2010-10-28 | Richter Gedeon Nyrt | Pharmaceutical composition for emergency contraception containing levonorgestrel |
| JP5037779B2 (ja) | 2002-02-21 | 2012-10-03 | バイエル ファーマ アクチエンゲゼルシャフト | １又は複数のステロイド、１又は複数のテトラヒドロ葉酸成分およびビタミンｂ１２を含む医薬組成物 |
| US20050147670A1 (en) | 2002-05-29 | 2005-07-07 | Impax Laboratories Inc. | Oral disintegrating dosage forms |
| US7943604B2 (en) | 2002-06-11 | 2011-05-17 | Pantarhei Bioscience B.V. | Method of treating human skin and a skin care composition for use in such a method |
| US7923440B2 (en) | 2002-06-11 | 2011-04-12 | Pantarhei Bioscience B.V. | Method of treating or preventing immune mediated disorders and pharmaceutical formulation for use therein |
| AU2003253506A1 (en) | 2002-07-12 | 2004-02-02 | Pantarhei Biosciences B.V. | Pharmaceutical composition comprising estetrol derivatives for use in cancer therapy |
| ATE380552T1 (de) | 2002-10-23 | 2007-12-15 | Pantarhei Bioscience Bv | Pharmazeutische zusammensetzung enthältend estetrolderivate und anwendung in der krebsbehandlung |
| EP1562976B1 (en) * | 2002-11-08 | 2010-05-26 | Pantarhei Bioscience B.V. | Synthesis of estetrol via estrone derived steroids |
| DK1624878T3 (da) | 2003-05-22 | 2007-01-08 | Pantarhei Bioscience Bv | Anvendelse af præparater som omfatter en östrogen komponent til behandling og forebyggelse af muskel-skelet-smerte |
| ES2388297T3 (es) | 2005-05-26 | 2012-10-11 | Abbott Products Gmbh | Inhibidores de 17-HSD1 y STS |
| EP2098592A3 (de) | 2005-07-25 | 2009-09-30 | Technische Universität Dresden | RNA-abhängige RNA-Polymerase, Verfahren und Kits zur Amplifikation und/oder Markierung von RNA |
| US20070048369A1 (en) | 2005-08-26 | 2007-03-01 | National Starch And Chemical Investment Holding Corporation | Mucosal delivery tablet |
| US20090221540A1 (en) | 2006-01-09 | 2009-09-03 | Pantarhei Bioscience B.V. | Method of Treating An Acute Vascular Disorder |
| US20070286819A1 (en) | 2006-06-08 | 2007-12-13 | Warner Chilcott Company, Inc. | Methods to administer ethinyl estradiol and prodrugs thereof with improved bioavailability |
| US20080113953A1 (en) | 2006-06-08 | 2008-05-15 | Warner Chilcott Company, Inc. | Methods to administer solid dosage forms of ethinyl estradiol and prodrugs thereof with improved bioavailability |
| EP2029146B8 (en) | 2006-06-08 | 2018-02-21 | Allergan Pharmaceuticals International Limited | Methods to administer solid dosage forms of ethinyl estradiol and prodrugs thereof with improved bioavailabilty |
| GB0621926D0 (en) | 2006-11-03 | 2006-12-13 | Medlock Medical Ltd | Multi directional stretch tubular bandages |
| AU2007325207A1 (en) | 2006-11-29 | 2008-06-05 | Wyeth | Estrogen/ serm and estrogen/ progestin bi-layer tablets |
| US7867515B2 (en) | 2006-12-20 | 2011-01-11 | TEVA Woman's Health, Inc. | Orally disintegrating solid dosage forms comprising progestin and methods of making and use thereof |
| CA2674325A1 (en) | 2007-01-08 | 2008-07-17 | Pantarhei Bioscience B.V. | Method of treating or preventing infertility in a female mammal and pharmaceutical kit for use in such method |
| AR064875A1 (es) | 2007-01-12 | 2009-04-29 | Wyeth Corp | Composiciones de tableta en tableta |
| US8367647B2 (en) | 2007-06-21 | 2013-02-05 | Pantarhei Bioscience B.V. | Treatment of meconium aspiration syndrome with estrogens |
| CA2693982C (en) | 2007-07-19 | 2017-03-14 | Pantarhei Bioscience B.V. | Treatment or prevention of hypertensive disorders of pregnancy or fetal growth retardation |
| CN101541725B (zh) | 2007-08-31 | 2013-08-28 | 国立大学法人名古屋大学 | 羰基化合物的制造方法和用于制造羰基化合物的氧化促进剂 |
| EP2077272A1 (en) | 2007-12-21 | 2009-07-08 | Affibody AB | Polypeptide libraries with a predetermined scaffold |
| EP2077273B1 (en) | 2007-12-31 | 2011-09-14 | Animal Technology Institute Taiwan | Methods for separating casein from soluble proteins in a composition |
| CN101318983A (zh) * | 2008-04-21 | 2008-12-10 | 上海大学 | 螺[(5β,6β,15β,16β-二亚甲基-雄甾-14β-氢-5,7-二烯-3-酮)-17α-2′-(1′-氧-环戊烷-5′-酮)]及其合成方法 |
| WO2010033832A2 (en) | 2008-09-19 | 2010-03-25 | Evestra, Inc. | Estriol formulations |
| DE102009007771B4 (de) | 2009-02-05 | 2012-02-16 | Bayer Schering Pharma Aktiengesellschaft | Bukkales Applikationssystem, 17α-Estradiol enthaltend |
| CN101560237A (zh) * | 2009-05-26 | 2009-10-21 | 上海大学 | 14β-氢-6β,7β,15β,16β-二亚甲基-3-氧代-17β-孕甾-4-烯-21,17-羧内酯及其合成方法 |
| CN102058604A (zh) | 2009-11-17 | 2011-05-18 | 北京万全阳光医学技术有限公司 | 一种含有地诺孕素和戊酸雌二醇的药物组合物及其制备方法 |
| US9603860B2 (en) | 2010-07-28 | 2017-03-28 | Laboratorios Leon Farma Sa | Pharmaceutical compositions comprising active drugs, contraceptive kits comprising active drugs, and methods of administering the same |
| ES2579175T3 (es) | 2011-06-01 | 2016-08-05 | Estetra S.P.R.L. | Proceso para la producción de intermediarios de estetrol |
| EA025511B1 (ru) | 2011-06-01 | 2016-12-30 | Эстетра С.П.Р.Л. | Способ получения промежуточных соединений эстетрола |
| KR102033187B1 (ko) | 2011-07-19 | 2019-10-16 | 판타레이 바이오사이언스 비.브이. | 디하이드로에피안드로스테론(ｄｈｅａ)을 함유하는 정제 |
| EP2383279A1 (en) | 2011-07-19 | 2011-11-02 | Pantarhei Bioscience B.V. | Process for the preparation of estetrol |
| ME02723B (me) | 2011-08-11 | 2017-10-20 | Estetra Sprl | Upotreba estetrola kao kontraceptivnog sredstva u hitnim slučajevima |
| BR112014005134A2 (pt) | 2011-09-16 | 2017-04-18 | Ferring Bv | composição farmacêutica de dissolução rápida |
| EP2764008B1 (en) | 2011-10-07 | 2016-08-17 | Estetra S.P.R.L. | Process for the production of estetrol |
| EP2653163A1 (en) | 2012-04-19 | 2013-10-23 | Université de Liège | Estrogenic components for use in the treatment of neurological disorders |
| US9808470B2 (en) | 2012-04-19 | 2017-11-07 | Universite De Liege | Estrogenic components for use in the treatment of neurological disorders |
| WO2014159377A1 (en) | 2013-03-14 | 2014-10-02 | Teva Women's Health, Inc. | Compositions containing tanaproget and natural estrogens |
| EP3046928B1 (en) | 2013-09-18 | 2017-02-08 | Crystal Pharma, S.A.U. | Process for the preparation of estetrol |
| EP3079671B1 (en) | 2013-12-12 | 2017-10-25 | Donesta Bioscience B.V. | Orally disintegrating solid dosage unit containing an estetrol component |
| CN107771075A (zh) | 2015-06-18 | 2018-03-06 | 密特拉制药公司 | 含雌四醇组分的口腔分散剂量单位 |
| MD3310345T2 (ro) | 2015-06-18 | 2021-07-31 | Estetra Sprl | Comprimată orodispersabilă ce conține estetrol |
| SI3701944T1 (sl) | 2015-06-18 | 2022-04-29 | Estetra Srl | Orodisperzibilna odmerna enota, ki vsebuje estetrolno komponento |
| CN107750157B (zh) | 2015-06-18 | 2021-07-13 | 埃斯特拉私人有限责任公司 | 含雌四醇的口腔分散片剂 |
-
2012
- 2012-06-01 EA EA201301315A patent/EA025511B1/ru unknown
- 2012-06-01 CN CN201280026131.6A patent/CN103619867B/zh active Active
- 2012-06-01 DK DK12729053.4T patent/DK2714712T3/en active
- 2012-06-01 JP JP2014513213A patent/JP6116550B2/ja active Active
- 2012-06-01 EP EP12729053.4A patent/EP2714712B1/en active Active
- 2012-06-01 US US14/122,892 patent/US11053273B2/en active Active
- 2012-06-01 RS RS20160946A patent/RS55293B1/sr unknown
- 2012-06-01 WO PCT/EP2012/060446 patent/WO2012164095A1/en active Application Filing
- 2012-06-01 MX MX2013014044A patent/MX342537B/es active IP Right Grant
- 2012-06-01 SG SG2013086715A patent/SG195121A1/en unknown
- 2012-06-01 PL PL12729053T patent/PL2714712T3/pl unknown
- 2012-06-01 CA CA2835979A patent/CA2835979C/en active Active
- 2012-06-01 BR BR112013030833A patent/BR112013030833B1/pt active IP Right Grant
- 2012-06-01 ME MEP-2016-253A patent/ME02585B/me unknown
- 2012-06-01 PT PT127290534T patent/PT2714712T/pt unknown
- 2012-06-01 HU HUE12729053A patent/HUE031809T2/en unknown
- 2012-06-01 SI SI201230746A patent/SI2714712T1/sl unknown
- 2012-06-01 KR KR1020137031484A patent/KR101957937B1/ko active IP Right Grant
- 2012-06-01 AU AU2012264601A patent/AU2012264601C1/en active Active
- 2012-06-01 ES ES12729053.4T patent/ES2600703T3/es active Active
- 2012-06-01 LT LTEP12729053.4T patent/LT2714712T/lt unknown
-
2013
- 2013-11-11 ZA ZA2013/08445A patent/ZA201308445B/en unknown
-
2016
- 2016-10-20 HR HRP20161369TT patent/HRP20161369T1/hr unknown
- 2016-10-26 CY CY20161101090T patent/CY1118164T1/el unknown
- 2016-11-10 SM SM201600408T patent/SMT201600408B/it unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| HRP20161369T1 (hr) | Postupak za proizvodnju intermedijera estetrola | |
| HRP20161282T1 (hr) | Postupak za proizvodnju estetrola | |
| IL263543A (en) | Methods and devices for synthesizing imaging agents, and their intermediates | |
| HRP20170851T1 (hr) | Postupak za proizvodnju cikloalkilkarboksiamido-piridin benzojevih kiselina | |
| RS54183B1 (en) | PIRAZOLE DERIVATIVES | |
| HRP20210764T1 (hr) | Postupak za pripremu 6-(ciklopropanamido)-4-((2-metoksi-3-(1-metil-1h-1,2,4-triazol-3-il)fenil)amino)-n-(metil-d3)piridazin-3-karboksamida | |
| RS51210B (sr) | Dobijanje pregaballina i srodnih jedinjenja | |
| JPWO2015190316A1 (ja) | ピリジン化合物の製造方法 | |
| CA2935601A1 (en) | 5-fluoro-4-imino-3-(alkyl/substituted alkyl)-1-(arylsulfonyl)-3,4-dihydropyrimidin-2(1h)-one and processes for their preparation | |
| HRP20130978T1 (hr) | Postupak priprave 6-(7-((1-aminociklopropil)metoksi)-6-metoksikinolin-4-iloksi)-n-metil-1-naftamid i odgovarajućih sintetičkih međuprodukata | |
| JP2015501820A5 (hr) | ||
| RU2007125710A (ru) | Способ получения n-фенилпиразол-1-карбоксамидов | |
| RU2009109160A (ru) | Инсектицидные изоксазолины | |
| RS51549B (en) | HETEROARIL UNITS USEFUL AS INVESTIGATIVE ENZYME E1 INHIBITORS | |
| NO20051051L (no) | Derivater av dioksan-2-alkylkarbamater, fremgangsmate for fremstilling derav og anvendelse av de samme i terapeutiske midler | |
| JP2008523069A5 (hr) | ||
| HRP20140856T1 (hr) | Postupak proizvodnje 2'-deoksi-5-azacitidina (decitabina) | |
| Cao et al. | A Highly Efficient CuCl2-Catalyzed C–S Coupling of Aryl Iodides with Tetraalkylthiuram Disulfides: Synthesis of Aryl Dithiocarbamates | |
| HRP20130103T1 (hr) | Postupak dobivanja montelukastove kiseline u ionskom tekuä†em mediju | |
| HRP20231191T1 (hr) | Postupak za proizvodnju n-(5-((4-(4-((dimetilamino)metil)-3-fenil-1h-pirazol-1-il)pirimidin-2-il)amino)-4-metoksi-2-morfolinofenil)akrilamida putem reakcije odgovarajućeg amina s 3-halo-propionilkloridom | |
| AR085023A1 (es) | Proceso para la preparacion de 4-amino-3-cloro-5-fluoro-6-picolinatos (sustituidos) e intermediario de dicha sintesis | |
| Mai et al. | Metal-free trifluoroethylation of activated alkenes: rapid access to construct fluorinated 3, 3-disubstituted 2-oxindoles | |
| JP4931181B2 (ja) | １８ｆ標識フルオロベンゼン環を有する放射性リガンドの合成法 | |
| CN108569942A (zh) | 一种α-三氟甲硫基取代苯乙酮类化合物的制备方法 | |
| CN103980280A (zh) | 一种酸性条件下合成喹唑啉酮并吲唑衍生物的方法 |