JP2008520688A - 選択的エストロゲン受容体モジュレーターとしての新規な２ｈ−クロメン誘導体 - Google Patents
選択的エストロゲン受容体モジュレーターとしての新規な２ｈ−クロメン誘導体 Download PDFInfo
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- JP2008520688A JP2008520688A JP2007543221A JP2007543221A JP2008520688A JP 2008520688 A JP2008520688 A JP 2008520688A JP 2007543221 A JP2007543221 A JP 2007543221A JP 2007543221 A JP2007543221 A JP 2007543221A JP 2008520688 A JP2008520688 A JP 2008520688A
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- alkyl
- group
- chromen
- ethoxy
- phenyl
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- 125000000850 2H-chromenyl group Chemical class O1C(C=CC2=CC=CC=C12)* 0.000 title abstract 2
- 239000000333 selective estrogen receptor modulator Substances 0.000 title description 7
- 229940095743 selective estrogen receptor modulator Drugs 0.000 title description 6
- 238000000034 method Methods 0.000 claims abstract description 46
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- 108010038795 estrogen receptors Proteins 0.000 claims abstract description 22
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 20
- 208000035475 disorder Diseases 0.000 claims abstract description 14
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 14
- 230000001404 mediated effect Effects 0.000 claims abstract description 11
- 150000001875 compounds Chemical class 0.000 claims description 152
- -1 carboxy, amino Chemical group 0.000 claims description 51
- 239000000203 mixture Substances 0.000 claims description 42
- 125000000217 alkyl group Chemical group 0.000 claims description 28
- 150000003839 salts Chemical class 0.000 claims description 22
- 239000000262 estrogen Substances 0.000 claims description 19
- 229910003849 O-Si Inorganic materials 0.000 claims description 17
- 229910003872 O—Si Inorganic materials 0.000 claims description 17
- 239000001257 hydrogen Substances 0.000 claims description 17
- 229910052739 hydrogen Inorganic materials 0.000 claims description 17
- 125000001424 substituent group Chemical group 0.000 claims description 17
- 229910052757 nitrogen Inorganic materials 0.000 claims description 16
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 15
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 13
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 13
- 239000003937 drug carrier Substances 0.000 claims description 12
- 125000005842 heteroatom Chemical group 0.000 claims description 12
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- 125000003545 alkoxy group Chemical group 0.000 claims description 10
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- 125000001072 heteroaryl group Chemical group 0.000 claims description 9
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
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- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 7
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- 125000006705 (C5-C7) cycloalkyl group Chemical group 0.000 claims description 5
- PAUMCYOKUFGQRG-UHFFFAOYSA-N 4-methyl-2-[4-(2-piperidin-1-ylethoxy)phenyl]-3-(2-trimethylsilylethoxymethyl)-2h-chromen-7-ol Chemical compound O1C2=CC(O)=CC=C2C(C)=C(COCC[Si](C)(C)C)C1C(C=C1)=CC=C1OCCN1CCCCC1 PAUMCYOKUFGQRG-UHFFFAOYSA-N 0.000 claims description 5
- 125000003118 aryl group Chemical group 0.000 claims description 5
- IFANTIOZECIHCH-UHFFFAOYSA-N 5-[4-(2-piperidin-1-ylethoxy)phenyl]-1,2,4,5-tetrahydropyrano[3,4-c]chromen-8-ol Chemical compound O1C2=CC(O)=CC=C2C(CCOC2)=C2C1C(C=C1)=CC=C1OCCN1CCCCC1 IFANTIOZECIHCH-UHFFFAOYSA-N 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000003386 piperidinyl group Chemical group 0.000 claims description 4
- RLJYJQLEYYYFCL-UHFFFAOYSA-N tert-butyl-dimethyl-[[5-[4-(2-piperidin-1-ylethoxy)phenyl]-1,2,4,5-tetrahydropyrano[3,4-c]chromen-8-yl]oxy]silane Chemical compound O1C2=CC(O[Si](C)(C)C(C)(C)C)=CC=C2C(CCOC2)=C2C1C(C=C1)=CC=C1OCCN1CCCCC1 RLJYJQLEYYYFCL-UHFFFAOYSA-N 0.000 claims description 4
- ZAOFBTDRLXTTRR-UHFFFAOYSA-N 4-methyl-2-[4-(2-piperidin-1-ylethoxy)phenyl]-2h-chromen-7-ol Chemical compound O1C2=CC(O)=CC=C2C(C)=CC1C(C=C1)=CC=C1OCCN1CCCCC1 ZAOFBTDRLXTTRR-UHFFFAOYSA-N 0.000 claims description 3
- YKALNUZJEDZKJG-UHFFFAOYSA-N 6-[4-(2-piperidin-1-ylethoxy)phenyl]-6,7,8,9,10,11-hexahydrocyclohepta[c]chromen-3-ol Chemical compound O1C2=CC(O)=CC=C2C(CCCCC2)=C2C1C(C=C1)=CC=C1OCCN1CCCCC1 YKALNUZJEDZKJG-UHFFFAOYSA-N 0.000 claims description 3
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- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 3
- 201000010881 cervical cancer Diseases 0.000 claims description 3
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- NMYMDQSWZHPVOQ-UHFFFAOYSA-N 2-[4-[2-(azepan-1-yl)ethoxy]phenyl]-4-(2-hydroxyethyl)-2h-chromen-7-ol Chemical compound O1C2=CC(O)=CC=C2C(CCO)=CC1C(C=C1)=CC=C1OCCN1CCCCCC1 NMYMDQSWZHPVOQ-UHFFFAOYSA-N 0.000 claims description 2
- BCAHYKSCCYDNLZ-UHFFFAOYSA-N 3-(hydroxymethyl)-4-methyl-2-[4-(2-piperidin-1-ylethoxy)phenyl]-2h-chromen-7-ol Chemical compound O1C2=CC(O)=CC=C2C(C)=C(CO)C1C(C=C1)=CC=C1OCCN1CCCCC1 BCAHYKSCCYDNLZ-UHFFFAOYSA-N 0.000 claims description 2
- FANGYSXRPPSHRV-UHFFFAOYSA-N 4-(2-hydroxyethyl)-2-[4-(2-piperidin-1-ylethoxy)phenyl]-2h-chromen-7-ol Chemical compound O1C2=CC(O)=CC=C2C(CCO)=CC1C(C=C1)=CC=C1OCCN1CCCCC1 FANGYSXRPPSHRV-UHFFFAOYSA-N 0.000 claims description 2
- SXENAAYLHGRIAZ-UHFFFAOYSA-N 4-cyclopentyl-2-[4-(2-piperidin-1-ylethoxy)phenyl]-2h-chromen-7-ol Chemical compound O1C2=CC(O)=CC=C2C(C2CCCC2)=CC1C(C=C1)=CC=C1OCCN1CCCCC1 SXENAAYLHGRIAZ-UHFFFAOYSA-N 0.000 claims description 2
- QYHKGMAAOCANDP-UHFFFAOYSA-N 6-[4-[2-(dimethylamino)ethoxy]phenyl]-6,7,8,9,10,11-hexahydrocyclohepta[c]chromen-3-ol Chemical compound C1=CC(OCCN(C)C)=CC=C1C1C(CCCCC2)=C2C2=CC=C(O)C=C2O1 QYHKGMAAOCANDP-UHFFFAOYSA-N 0.000 claims description 2
- 125000003282 alkyl amino group Chemical group 0.000 claims description 2
- 125000002785 azepinyl group Chemical group 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 201000006828 endometrial hyperplasia Diseases 0.000 claims 3
- PAUMCYOKUFGQRG-LJAQVGFWSA-N (2s)-4-methyl-2-[4-(2-piperidin-1-ylethoxy)phenyl]-3-(2-trimethylsilylethoxymethyl)-2h-chromen-7-ol Chemical compound C1=CC([C@H]2C(COCC[Si](C)(C)C)=C(C3=CC=C(O)C=C3O2)C)=CC=C1OCCN1CCCCC1 PAUMCYOKUFGQRG-LJAQVGFWSA-N 0.000 claims 2
- 206010060862 Prostate cancer Diseases 0.000 claims 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims 2
- PAUMCYOKUFGQRG-GDLZYMKVSA-N (2r)-4-methyl-2-[4-(2-piperidin-1-ylethoxy)phenyl]-3-(2-trimethylsilylethoxymethyl)-2h-chromen-7-ol Chemical compound C1=CC([C@@H]2C(COCC[Si](C)(C)C)=C(C3=CC=C(O)C=C3O2)C)=CC=C1OCCN1CCCCC1 PAUMCYOKUFGQRG-GDLZYMKVSA-N 0.000 claims 1
- 125000006704 (C5-C6) cycloalkyl group Chemical group 0.000 claims 1
- 238000011278 co-treatment Methods 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 33
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 138
- 239000011541 reaction mixture Substances 0.000 description 93
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 78
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 77
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- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 44
- 239000012044 organic layer Substances 0.000 description 43
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 42
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 42
- 229910052938 sodium sulfate Inorganic materials 0.000 description 42
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Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
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- A—HUMAN NECESSITIES
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/06—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2
- C07D311/08—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring
- C07D311/18—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring substituted otherwise than in position 3 or 7
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
- C07D311/60—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4 with aryl radicals attached in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/78—Ring systems having three or more relevant rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
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- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Diabetes (AREA)
- Rheumatology (AREA)
- Gynecology & Obstetrics (AREA)
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- Biomedical Technology (AREA)
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- Neurology (AREA)
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- Hematology (AREA)
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- Immunology (AREA)
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- Hospice & Palliative Care (AREA)
- Pregnancy & Childbirth (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyrane Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US62898704P | 2004-11-18 | 2004-11-18 | |
| PCT/US2005/041648 WO2006055694A1 (en) | 2004-11-18 | 2005-11-17 | Novel 2h-chromene derivatives as selective estrogen receptor modulators |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2008520688A true JP2008520688A (ja) | 2008-06-19 |
| JP2008520688A5 JP2008520688A5 (cg-RX-API-DMAC7.html) | 2009-01-15 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007543221A Withdrawn JP2008520688A (ja) | 2004-11-18 | 2005-11-17 | 選択的エストロゲン受容体モジュレーターとしての新規な２ｈ−クロメン誘導体 |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US20060166933A1 (cg-RX-API-DMAC7.html) |
| EP (1) | EP1812417B1 (cg-RX-API-DMAC7.html) |
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| CN (1) | CN101103011A (cg-RX-API-DMAC7.html) |
| AT (1) | ATE412643T1 (cg-RX-API-DMAC7.html) |
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| CA (1) | CA2587669A1 (cg-RX-API-DMAC7.html) |
| DE (1) | DE602005010735D1 (cg-RX-API-DMAC7.html) |
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| PT (1) | PT1812417E (cg-RX-API-DMAC7.html) |
| SI (1) | SI1812417T1 (cg-RX-API-DMAC7.html) |
| WO (1) | WO2006055694A1 (cg-RX-API-DMAC7.html) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2018520116A (ja) * | 2015-05-26 | 2018-07-26 | エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト | 複素環式エストロゲン受容体モジュレーター及びその使用 |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20200390755A1 (en) * | 2018-08-01 | 2020-12-17 | Shaanxi Micot Technology Co., Ltd. | Compound for treating nervous system diseases and use thereof |
| CN119176799B (zh) * | 2024-09-19 | 2025-10-03 | 晨伫(杭州)生物科技有限责任公司 | 色烯衍生物及其应用 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6060503A (en) * | 1991-12-02 | 2000-05-09 | Endorecherche, Inc. | Benzopyran-containing compounds and method for their use |
| DE10013782A1 (de) * | 2000-03-15 | 2001-10-18 | Schering Ag | 4-Fluoralkyl-2H-benzopyrane mit antiestrogener Wirksamkeit, Verfahren zu ihrer Herstellung, pharmazeutische Präparate, die diese enthalten sowie deren Verwendung zur Herstellung von Arzneimitteln |
| IL161325A0 (en) * | 2001-11-19 | 2004-09-27 | Lilly Co Eli | Substituted benzopyrans as selective estrogen receptor-beta agonists |
| US7329654B2 (en) * | 2001-12-19 | 2008-02-12 | Janssen Pharmaceutica N.V. | Heteroatom containing tetracyclic derivatives as selective estrogen receptor modulators |
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- 2005-11-17 CN CNA2005800468519A patent/CN101103011A/zh active Pending
- 2005-11-17 ES ES05824228T patent/ES2314747T3/es not_active Expired - Lifetime
- 2005-11-17 SI SI200530558T patent/SI1812417T1/sl unknown
- 2005-11-17 JP JP2007543221A patent/JP2008520688A/ja not_active Withdrawn
- 2005-11-17 PL PL05824228T patent/PL1812417T3/pl unknown
- 2005-11-17 DE DE602005010735T patent/DE602005010735D1/de not_active Expired - Fee Related
- 2005-11-17 US US11/281,074 patent/US20060166933A1/en not_active Abandoned
- 2005-11-17 WO PCT/US2005/041648 patent/WO2006055694A1/en not_active Ceased
- 2005-11-17 PT PT05824228T patent/PT1812417E/pt unknown
- 2005-11-17 CA CA002587669A patent/CA2587669A1/en not_active Abandoned
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- 2005-11-17 AT AT05824228T patent/ATE412643T1/de not_active IP Right Cessation
- 2005-11-17 EP EP05824228A patent/EP1812417B1/en not_active Expired - Lifetime
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2018520116A (ja) * | 2015-05-26 | 2018-07-26 | エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト | 複素環式エストロゲン受容体モジュレーター及びその使用 |
Also Published As
| Publication number | Publication date |
|---|---|
| PL1812417T3 (pl) | 2009-04-30 |
| SI1812417T1 (sl) | 2009-04-30 |
| EP1812417A1 (en) | 2007-08-01 |
| CA2587669A1 (en) | 2006-05-26 |
| DK1812417T3 (da) | 2009-02-16 |
| DE602005010735D1 (de) | 2008-12-11 |
| WO2006055694A1 (en) | 2006-05-26 |
| EP1812417B1 (en) | 2008-10-29 |
| ES2314747T3 (es) | 2009-03-16 |
| AU2005307704A1 (en) | 2006-05-26 |
| US20060166933A1 (en) | 2006-07-27 |
| CN101103011A (zh) | 2008-01-09 |
| ATE412643T1 (de) | 2008-11-15 |
| PT1812417E (pt) | 2008-12-05 |
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