HUP0500025A2 - Tisztított lasofoxifene és eljárás racém lasofoxifene tisztítására átkristályosítással - Google Patents
Tisztított lasofoxifene és eljárás racém lasofoxifene tisztítására átkristályosítással Download PDFInfo
- Publication number
- HUP0500025A2 HUP0500025A2 HU0500025A HUP0500025A HUP0500025A2 HU P0500025 A2 HUP0500025 A2 HU P0500025A2 HU 0500025 A HU0500025 A HU 0500025A HU P0500025 A HUP0500025 A HU P0500025A HU P0500025 A2 HUP0500025 A2 HU P0500025A2
- Authority
- HU
- Hungary
- Prior art keywords
- phenyl
- lasofoxifene
- purified
- ethanol
- racemic
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 20
- 238000000746 purification Methods 0.000 title claims description 18
- GXESHMAMLJKROZ-IAPPQJPRSA-N lasofoxifene Chemical compound C1([C@@H]2[C@@H](C3=CC=C(C=C3CC2)O)C=2C=CC(OCCN3CCCC3)=CC=2)=CC=CC=C1 GXESHMAMLJKROZ-IAPPQJPRSA-N 0.000 title description 91
- 229960002367 lasofoxifene Drugs 0.000 title description 86
- 238000001953 recrystallisation Methods 0.000 title description 5
- 239000012535 impurity Substances 0.000 claims abstract description 36
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 94
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 64
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 32
- 239000000725 suspension Substances 0.000 claims description 30
- 239000000203 mixture Substances 0.000 claims description 20
- 239000007787 solid Substances 0.000 claims description 18
- 238000001914 filtration Methods 0.000 claims description 14
- 238000003756 stirring Methods 0.000 claims description 4
- 238000001816 cooling Methods 0.000 claims description 3
- 238000010438 heat treatment Methods 0.000 claims description 3
- 239000000556 agonist Substances 0.000 abstract description 3
- 229940011871 estrogen Drugs 0.000 abstract description 3
- 239000000262 estrogen Substances 0.000 abstract description 3
- 239000005557 antagonist Substances 0.000 abstract description 2
- UMKXSOXZAXIOPJ-UHFFFAOYSA-N 5,6,7,8-tetrahydro-2-naphthol Chemical compound C1CCCC2=CC(O)=CC=C21 UMKXSOXZAXIOPJ-UHFFFAOYSA-N 0.000 abstract 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 12
- 230000014759 maintenance of location Effects 0.000 description 12
- 230000002265 prevention Effects 0.000 description 7
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- FEWJPZIEWOKRBE-LWMBPPNESA-L D-tartrate(2-) Chemical compound [O-]C(=O)[C@@H](O)[C@H](O)C([O-])=O FEWJPZIEWOKRBE-LWMBPPNESA-L 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000000328 estrogen antagonist Substances 0.000 description 2
- 229940095743 selective estrogen receptor modulator Drugs 0.000 description 2
- 239000000333 selective estrogen receptor modulator Substances 0.000 description 2
- JEHUZVBIUCAMRZ-UHFFFAOYSA-N 1,1'-binaphthyl-2,2'-diyl hydrogenphosphate Chemical compound O1P(O)(=O)OC2=CC=C(C=CC=C3)C3=C2C2=C1C=CC1=CC=CC=C21 JEHUZVBIUCAMRZ-UHFFFAOYSA-N 0.000 description 1
- 208000037853 Abnormal uterine bleeding Diseases 0.000 description 1
- 206010000242 Abortion threatened Diseases 0.000 description 1
- 208000002874 Acne Vulgaris Diseases 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 208000005171 Dysmenorrhea Diseases 0.000 description 1
- 201000009273 Endometriosis Diseases 0.000 description 1
- 208000008899 Habitual abortion Diseases 0.000 description 1
- 206010020112 Hirsutism Diseases 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- 206010027304 Menopausal symptoms Diseases 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000004403 Prostatic Hyperplasia Diseases 0.000 description 1
- 208000005985 Threatened Abortion Diseases 0.000 description 1
- 206010000496 acne Diseases 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 229940046836 anti-estrogen Drugs 0.000 description 1
- 230000001833 anti-estrogenic effect Effects 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 229960001270 d- tartaric acid Drugs 0.000 description 1
- 230000006408 female gonad development Effects 0.000 description 1
- 230000003779 hair growth Effects 0.000 description 1
- 230000006651 lactation Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 229940127234 oral contraceptive Drugs 0.000 description 1
- 239000003539 oral contraceptive agent Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 238000013341 scale-up Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/06—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with radicals, containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/088—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
-
- 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
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Diabetes (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Endocrinology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyrrole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
A találmány tárgya eljárás szennyezőanyagok eltávolítására racém cisz-6-fenil-[4-(2-pirrolidin-l-iletoxi)fenil]-5,6,7,8-tetrahidronaftalin-2-olból, valamint a tisztított cisz-6-fenil-[4-(2-pirrolidin-l-iletoxi)fenil]5,6,7,8-tetrahidronaftalin-2-ol, amely ösztrogénagonistaként/antagonistaként alkalmazható. Ó
Claims (12)
- Szabadalmi igénypontok1. Eljárás racém cisz-6-fenil-[4-(2-pirrolidin-liletoxi)fenil]-5,6,7,8-tetrahidronaftalin-2-ol tisztítására, azzal jellemezve, hogya) racém cisz-6-fenil-[4-(2-pirrolidin-l-iletoxi)fenil] -5 , 6 , 7 , 8 -tetrahidronaf talin-2-olt etanol és tetrahidrofurán elegyében szuszpendálunk,b) a kapott szuszpenziót keverjük és melegítjük, c) a b) lépésben kapott szuszpenziőt lehűtjük, és d) a szilárd tisztított racém cisz-6-fenil-[4-(2-pirrolidin-l-iletoxi)fenil]-5,6,7,8-tetrahidronaftalin-2-olt kinyerjük.
- 2. Az 1. igénypont szerinti eljárás, azzal jellemezve, hogy az etanolt és a tetrahidrofuránt körülbelül 4:1 térfogatarányban alkalmazzuk.
- 3. Az 1. igénypont szerinti eljárás, azzal jellemezve, hogy az etanolt és a tetrahidrofuránt körülbelül 3:1 térfogatarányban alkalmazzuk.
- 4. Az 1. igénypont szerinti eljárás, azzal jellemezve, hogy az etanolt és a tetrahidrofuránt körülbelül 2:1 térfogatarányban alkalmazzuk.
- 5. Az 1. igénypont szerinti eljárás, azzal jellemezve, hogy az etanolt és a tetrahidrofuránt körülbelül 1:1 térfogatarányban alkalmazzuk.
- 6. Az 1-5. igénypontok bármelyike szerinti eljárás, azzal jellemezve, hogy az a) lépésben kapott szuszpenziót a b) lépésben környezeti hőmérséklet és körülbelül 70 °C közötti hőmérsékleten melegítjük és keverjük.
- 7. A 6. igénypont szerinti eljárás, azzal jellemezve, hogy az a) lépésben kapott szuszpenziót a b) lépésben környezeti hőmérséklet és körülbelül 65 °C közötti hőmérsékleten körülbelül 12 óráig terjedő ideig melegítjük és kever j ük.
- 8. A 7. igénypont szerinti eljárás, azzal jellemezve, hogy a b) lépésben kapott szuszpenziót a c) lépésben körülbelül 18 óráig terjedő ideig hűtjük és keverjük.
- 9. A 8. igénypont szerinti eljárás, azzal jellemezve, hogy a c) lépésben kapott szuszpenziót szűrjük, így szilárd, tisztított racém cisz-6-fenil-[4-(2-pirrolidin-l-iletoxi)fenil]-5,6,7,8-tetrahidronaftalin-2-olt kapunk, amely 0,2%-nál kevesebb szennyezőanyagot tartalmaz.
- 10. A 8. igénypont szerinti eljárás, azzal jellemezve, hogy a c) lépésben kapott szuszpenziót szűrjük, így szilárd, tisztított racém cisz-6-fenil-[4-(2-pirrolidin-liletoxi)fenil]-5,6,7,8-tetrahidronaftalin-2-olt kapunk, amely 0,1%-nál kevesebb szennyezőanyagot tartalmaz.
- 11. Eljárás racém cisz-6-fenil-[4-(2-pirrolidin-1iletoxi)fenil]-5,6,7,8-tetrahidronaftalin-2-ol tisztítására, azzal jellemezve, hogya) racém cisz-6-fenil-[4-(2-pirrolidin-l-iletoxi)fenil] -5,6,7,8-tetrahidronaftalin-2-olt etanol és tetrahidrofurán 2:1 térfogatarányú elegyében szuszpendálunk,b) a kapott szuszpenziót környezeti és 65 °C közötti hőmérsékleten 12 óráig terjedő ideig keverjük és melegítjük,c) a b) lépésben kapott szuszpenziót lehűtjük, és 18 óráig terjedő ideig keverjük, ésd) a szilárd racém cisz-6-fenil-[4-(2-pirrolidin-liletoxi) fenil]-5,6,7,8-tetrahidronaftalin-2-olt szűréssel kinyerj ük.
- 12. Tisztított cisz-6-fenil-[4-(2-pirrolidin-l-iletoxi) fenil]-5,6,7,8-tetrahidronaftalin-2-ol, amely 0,1%nál kevesebb szennyezőanyagot tartalmaz.A meghatalmazott:Dr. Gárdonyi Zoltánná ^jjsaahadalmi ügyvivő
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US36887202P | 2002-03-28 | 2002-03-28 | |
| PCT/IB2003/001033 WO2003082814A1 (en) | 2002-03-28 | 2003-03-17 | Purified lasofoxifene and a method for purification of racemic lasofoxifene by recrystallization |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| HUP0500025A2 true HUP0500025A2 (hu) | 2005-04-28 |
| HUP0500025A3 HUP0500025A3 (en) | 2005-10-28 |
Family
ID=28675551
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HU0500025A HUP0500025A3 (en) | 2002-03-28 | 2003-03-17 | Purified lasofoxifene and a method for purification of racemic lasofoxifene by recrystallization |
Country Status (23)
| Country | Link |
|---|---|
| US (2) | US6906202B2 (hu) |
| EP (1) | EP1487790B1 (hu) |
| JP (1) | JP4268055B2 (hu) |
| KR (1) | KR100636953B1 (hu) |
| CN (1) | CN1283625C (hu) |
| AR (1) | AR039152A1 (hu) |
| AT (1) | ATE459599T1 (hu) |
| AU (1) | AU2003209603B2 (hu) |
| BR (1) | BR0308758A (hu) |
| CA (1) | CA2479924C (hu) |
| DE (1) | DE60331527D1 (hu) |
| DK (1) | DK1487790T3 (hu) |
| ES (1) | ES2339936T3 (hu) |
| HK (1) | HK1073111A1 (hu) |
| HU (1) | HUP0500025A3 (hu) |
| IL (2) | IL162929A0 (hu) |
| MX (1) | MXPA04009259A (hu) |
| PL (1) | PL372727A1 (hu) |
| RS (1) | RS80604A (hu) |
| RU (1) | RU2278861C2 (hu) |
| TW (1) | TW200306974A (hu) |
| WO (1) | WO2003082814A1 (hu) |
| ZA (1) | ZA200405209B (hu) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL162929A0 (en) * | 2002-03-28 | 2005-11-20 | Pfizer Prod Inc | Purified lasofoxifene and a method for purification of racemic lasofoxifene by recrystallization |
| US7795427B2 (en) * | 2006-02-14 | 2010-09-14 | New York University | Methods for inhibiting osteoclast differentiation, formation, or function and for increasing bone mass |
| CZ2007373A3 (cs) * | 2007-05-29 | 2008-12-10 | Zentiva, A. S | Zpusob prípravy lasofoxifenu |
| CN102311406A (zh) * | 2010-06-29 | 2012-01-11 | 武汉启瑞药业有限公司 | 拉索昔芬中间体的制备方法 |
| JP6892151B2 (ja) | 2016-10-11 | 2021-06-23 | デューク ユニバーシティ | Ｅｒ＋乳がんのラソフォキシフェン処置 |
| WO2019199891A1 (en) | 2018-04-10 | 2019-10-17 | Duke University | Lasofoxifene treatment of breast cancer |
| KR102412089B1 (ko) | 2021-09-13 | 2022-06-22 | 주식회사 세라수 | Dmts의 정제방법 |
| GB202116903D0 (en) | 2021-11-18 | 2022-01-05 | Sermonix Pharmaceuticals Inc | Lasofoxifene treatment of aromatase-resistant er+ cancer |
| WO2025043004A1 (en) | 2023-08-21 | 2025-02-27 | Duke University | Treatment of solid cancer with lasofoxifene |
| KR102663941B1 (ko) | 2024-03-04 | 2024-05-08 | 주식회사 세라수 | Drometrizole trisiloxane(DMTS)의 제조방법 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5326865A (en) * | 1990-06-08 | 1994-07-05 | Hercules Incorporated | Arylazo and poly(arylazo) dyes having at least one core radical selected from naphthyl or anthracyl and having at least one 2,3-dihydro-1,3-dialkyl perimidine substituent |
| US5552412A (en) * | 1995-01-09 | 1996-09-03 | Pfizer Inc | 5-substitued-6-cyclic-5,6,7,8-tetrahydronaphthalen2-ol compounds which are useful for treating osteoporosis |
| EP0756205A3 (en) * | 1995-07-26 | 1998-10-14 | Eastman Kodak Company | Pattern transfer techniques for fabrication of lenslet arrays using specialized polyesters |
| UA51676C2 (uk) | 1995-11-02 | 2002-12-16 | Пфайзер Інк. | (-)цис-6(s)-феніл-5(r)[4-(2-піролідин-1-ілетокси)феніл]-5,6,7,8-тетрагідронафталін-2-ол d-тартрат, спосіб його одержання, спосіб лікування захворювань, що піддаються лікуванню агоністами естрогену, та фармацевтична композиція |
| YU26700A (sh) * | 1999-05-24 | 2002-06-19 | Pfizer Products Inc. | Postupak za cis-1-(2-(4-(6-metoksi-2-fenil-1,2,3,4- tetrahidronaftalen-1-il)fenoksi)etil)pirolidin |
| US6180375B1 (en) * | 1999-08-27 | 2001-01-30 | Pfizer Inc. | Microbial biotransformation |
| KR100568380B1 (ko) | 2001-05-01 | 2006-04-05 | 화이자 프로덕츠 인코포레이티드 | 저 투약량 약학 조성물의 제조 방법 |
| IL162929A0 (en) * | 2002-03-28 | 2005-11-20 | Pfizer Prod Inc | Purified lasofoxifene and a method for purification of racemic lasofoxifene by recrystallization |
-
2003
- 2003-03-17 IL IL16292903A patent/IL162929A0/xx unknown
- 2003-03-17 CA CA002479924A patent/CA2479924C/en not_active Expired - Fee Related
- 2003-03-17 AT AT03745203T patent/ATE459599T1/de not_active IP Right Cessation
- 2003-03-17 AU AU2003209603A patent/AU2003209603B2/en not_active Ceased
- 2003-03-17 JP JP2003580282A patent/JP4268055B2/ja not_active Expired - Fee Related
- 2003-03-17 DE DE60331527T patent/DE60331527D1/de not_active Expired - Lifetime
- 2003-03-17 MX MXPA04009259A patent/MXPA04009259A/es active IP Right Grant
- 2003-03-17 KR KR1020047015249A patent/KR100636953B1/ko not_active Expired - Fee Related
- 2003-03-17 RU RU2004128931/04A patent/RU2278861C2/ru not_active IP Right Cessation
- 2003-03-17 BR BR0308758-1A patent/BR0308758A/pt not_active IP Right Cessation
- 2003-03-17 PL PL03372727A patent/PL372727A1/xx not_active Application Discontinuation
- 2003-03-17 DK DK03745203.4T patent/DK1487790T3/da active
- 2003-03-17 RS YUP-806/04A patent/RS80604A/sr unknown
- 2003-03-17 CN CNB038031175A patent/CN1283625C/zh not_active Expired - Lifetime
- 2003-03-17 ES ES03745203T patent/ES2339936T3/es not_active Expired - Lifetime
- 2003-03-17 EP EP03745203A patent/EP1487790B1/en not_active Expired - Lifetime
- 2003-03-17 HU HU0500025A patent/HUP0500025A3/hu unknown
- 2003-03-17 WO PCT/IB2003/001033 patent/WO2003082814A1/en not_active Application Discontinuation
- 2003-03-26 US US10/397,654 patent/US6906202B2/en not_active Expired - Lifetime
- 2003-03-26 AR ARP030101058A patent/AR039152A1/es unknown
- 2003-03-27 TW TW092106928A patent/TW200306974A/zh unknown
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2004
- 2004-06-30 ZA ZA2004/05209A patent/ZA200405209B/en unknown
- 2004-07-08 IL IL162929A patent/IL162929A/en active IP Right Grant
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2005
- 2005-03-28 US US11/092,240 patent/US7358374B2/en not_active Expired - Lifetime
- 2005-07-11 HK HK05105808A patent/HK1073111A1/xx not_active IP Right Cessation
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