DE102004012069A1 - Neue aryl-haltige 5-Acylindolinone, deren Herstellung und deren Verwendung als Arzneimittel - Google Patents
Neue aryl-haltige 5-Acylindolinone, deren Herstellung und deren Verwendung als Arzneimittel Download PDFInfo
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- DE102004012069A1 DE102004012069A1 DE102004012069A DE102004012069A DE102004012069A1 DE 102004012069 A1 DE102004012069 A1 DE 102004012069A1 DE 102004012069 A DE102004012069 A DE 102004012069A DE 102004012069 A DE102004012069 A DE 102004012069A DE 102004012069 A1 DE102004012069 A1 DE 102004012069A1
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- Prior art keywords
- alkyl
- group
- substituted
- amino
- indolinone
- Prior art date
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- 125000003118 aryl group Chemical group 0.000 title claims abstract description 6
- 238000002360 preparation method Methods 0.000 title claims description 13
- 239000003814 drug Substances 0.000 title claims description 9
- 239000000203 mixture Substances 0.000 claims abstract description 27
- 150000003839 salts Chemical class 0.000 claims abstract description 27
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims abstract description 18
- 150000001875 compounds Chemical class 0.000 claims description 68
- 125000000217 alkyl group Chemical group 0.000 claims description 59
- -1 nitro, cyano, Amino Chemical group 0.000 claims description 53
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 40
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 35
- 229910052757 nitrogen Inorganic materials 0.000 claims description 28
- 125000006698 (C1-C3) dialkylamino group Chemical group 0.000 claims description 27
- 125000003545 alkoxy group Chemical group 0.000 claims description 26
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 24
- 125000001424 substituent group Chemical group 0.000 claims description 22
- 239000000460 chlorine Chemical group 0.000 claims description 20
- 239000000126 substance Substances 0.000 claims description 18
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 17
- 229910052801 chlorine Inorganic materials 0.000 claims description 16
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 15
- 229910052731 fluorine Inorganic materials 0.000 claims description 15
- 239000011737 fluorine Substances 0.000 claims description 15
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 14
- 125000004432 carbon atom Chemical group C* 0.000 claims description 14
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 12
- 229910052794 bromium Chemical group 0.000 claims description 12
- 125000006597 (C1-C3) alkylcarbonylamino group Chemical group 0.000 claims description 11
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 10
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 10
- 125000006239 protecting group Chemical group 0.000 claims description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
- 238000006243 chemical reaction Methods 0.000 claims description 8
- 206010012601 diabetes mellitus Diseases 0.000 claims description 8
- 125000001072 heteroaryl group Chemical group 0.000 claims description 8
- 125000005842 heteroatom Chemical group 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 7
- 208000024827 Alzheimer disease Diseases 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- 125000006842 cycloalkyleneimino group Chemical group 0.000 claims description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
- ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical group O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- 150000001412 amines Chemical class 0.000 claims description 5
- 125000003277 amino group Chemical group 0.000 claims description 5
- 125000001246 bromo group Chemical group Br* 0.000 claims description 5
- 125000001153 fluoro group Chemical group F* 0.000 claims description 5
- 125000002883 imidazolyl group Chemical group 0.000 claims description 5
- 150000007522 mineralic acids Chemical class 0.000 claims description 5
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- 235000005985 organic acids Nutrition 0.000 claims description 5
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- 125000006602 (C1-C3) alkylsulfonylamino group Chemical group 0.000 claims description 4
- ITFRWUWWMCAPJX-OCOZRVBESA-N 4-[[(e)-(5-acetyl-2-oxo-1h-indol-3-ylidene)-(2,3-dihydro-1,4-benzodioxin-6-yl)methyl]amino]benzonitrile Chemical compound C12=CC(C(=O)C)=CC=C2NC(=O)\C1=C(C=1C=C2OCCOC2=CC=1)\NC1=CC=C(C#N)C=C1 ITFRWUWWMCAPJX-OCOZRVBESA-N 0.000 claims description 4
- PBKNRZLAHOHFJY-UHFFFAOYSA-N 5-acetyl-3-[[4-[(dimethylamino)methyl]anilino]-(3-methoxyphenyl)methylidene]-1h-indol-2-one Chemical compound COC1=CC=CC(C(NC=2C=CC(CN(C)C)=CC=2)=C2C3=CC(=CC=C3NC2=O)C(C)=O)=C1 PBKNRZLAHOHFJY-UHFFFAOYSA-N 0.000 claims description 4
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- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 150000003951 lactams Chemical group 0.000 claims description 4
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 125000006563 (C1-3) alkylaminocarbonyl group Chemical group 0.000 claims description 3
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- 239000000969 carrier Substances 0.000 claims description 3
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- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 3
- 229910052740 iodine Inorganic materials 0.000 claims description 3
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 3
- 125000006594 (C1-C3) alkylsulfony group Chemical group 0.000 claims description 2
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 2
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 2
- QNFNCWDZCWGVHH-UHFFFAOYSA-N 5-acetyl-3-[(3,5-dimethoxyphenyl)-[4-[(dimethylamino)methyl]anilino]methylidene]-1h-indol-2-one Chemical compound COC1=CC(OC)=CC(C(NC=2C=CC(CN(C)C)=CC=2)=C2C3=CC(=CC=C3NC2=O)C(C)=O)=C1 QNFNCWDZCWGVHH-UHFFFAOYSA-N 0.000 claims description 2
- PXKZNTZKSOMKQE-UHFFFAOYSA-N 5-acetyl-3-[[4-(diethylaminomethyl)anilino]-phenylmethylidene]-1h-indol-2-one Chemical compound C1=CC(CN(CC)CC)=CC=C1NC(C=1C=CC=CC=1)=C1C2=CC(C(C)=O)=CC=C2NC1=O PXKZNTZKSOMKQE-UHFFFAOYSA-N 0.000 claims description 2
- HGSWEDDINXUSQV-UHFFFAOYSA-N 5-acetyl-3-[[4-(ethylaminomethyl)anilino]-phenylmethylidene]-1h-indol-2-one Chemical compound C1=CC(CNCC)=CC=C1NC(C=1C=CC=CC=1)=C1C2=CC(C(C)=O)=CC=C2NC1=O HGSWEDDINXUSQV-UHFFFAOYSA-N 0.000 claims description 2
- 125000004657 aryl sulfonyl amino group Chemical group 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000002619 bicyclic group Chemical group 0.000 claims description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 2
- 230000006378 damage Effects 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 125000005544 phthalimido group Chemical group 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 125000003107 substituted aryl group Chemical group 0.000 claims description 2
- RKTSCIZXPPGSJB-UHFFFAOYSA-N 5-acetyl-3-[2,3-dihydro-1,4-benzodioxin-6-yl-[4-[(dimethylamino)methyl]anilino]methylidene]-1h-indol-2-one Chemical compound C1=CC(CN(C)C)=CC=C1NC(C=1C=C2OCCOC2=CC=1)=C1C2=CC(C(C)=O)=CC=C2NC1=O RKTSCIZXPPGSJB-UHFFFAOYSA-N 0.000 claims 1
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims 1
- 125000000547 substituted alkyl group Chemical group 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 12
- 230000002401 inhibitory effect Effects 0.000 abstract description 5
- 230000000144 pharmacologic effect Effects 0.000 abstract description 3
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- 238000001819 mass spectrum Methods 0.000 description 68
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- OGDZTLONCPVKCE-UHFFFAOYSA-N 1,5-diacetyl-3h-indol-2-one Chemical compound CC(=O)C1=CC=C2N(C(=O)C)C(=O)CC2=C1 OGDZTLONCPVKCE-UHFFFAOYSA-N 0.000 description 28
- 239000013543 active substance Substances 0.000 description 21
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- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 16
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- AKGNIBXGIPMDLE-UHFFFAOYSA-N pyridine-4-carboxylic acid Chemical compound OC(=O)C1=CC=NC=C1.OC(=O)C1=CC=NC=C1 AKGNIBXGIPMDLE-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/32—Oxygen atoms
- C07D209/34—Oxygen atoms in position 2
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Psychiatry (AREA)
- Psychology (AREA)
- Cardiology (AREA)
- Pain & Pain Management (AREA)
- Dermatology (AREA)
- Immunology (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Child & Adolescent Psychology (AREA)
- Urology & Nephrology (AREA)
- Hospice & Palliative Care (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Priority Applications (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE102004012069A DE102004012069A1 (de) | 2004-03-12 | 2004-03-12 | Neue aryl-haltige 5-Acylindolinone, deren Herstellung und deren Verwendung als Arzneimittel |
| PCT/EP2005/002405 WO2005087726A1 (de) | 2004-03-12 | 2005-03-05 | Neue aryl-haltige 5-acylindolinone, deren herstellung und deren verwendung als arzneimittel |
| JP2007502260A JP2007528882A (ja) | 2004-03-12 | 2005-03-05 | 新規なアリール含有５−アシルインドリノン、その製法及びその医薬品としての使用 |
| DE502005005809T DE502005005809D1 (de) | 2004-03-12 | 2005-03-05 | Neue aryl-haltige 5-acylindolinone, deren herstellung und deren verwendung als arzneimittel |
| CA002559115A CA2559115A1 (en) | 2004-03-12 | 2005-03-05 | Novel aryl-containing 5-acylindolinones, the production thereof and their use as medicaments |
| ES05715810T ES2317201T3 (es) | 2004-03-12 | 2005-03-05 | Nuevas 5-acil-indolinonas que contienen arilo, obtencion de las mismas y su utilizacion como medicamentos. |
| AT05715810T ATE412632T1 (de) | 2004-03-12 | 2005-03-05 | Neue aryl-haltige 5-acylindolinone, deren herstellung und deren verwendung als arzneimittel |
| EP05715810A EP1727798B1 (de) | 2004-03-12 | 2005-03-05 | Neue aryl-haltige 5-acylindolinone, deren herstellung und deren verwendung als arzneimittel |
| US11/077,259 US7176231B2 (en) | 2004-03-12 | 2005-03-10 | Aryl-containing 5-acylindolinones, the preparation thereof and their use as medicaments |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE102004012069A DE102004012069A1 (de) | 2004-03-12 | 2004-03-12 | Neue aryl-haltige 5-Acylindolinone, deren Herstellung und deren Verwendung als Arzneimittel |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE102004012069A1 true DE102004012069A1 (de) | 2005-09-29 |
Family
ID=34895264
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE102004012069A Withdrawn DE102004012069A1 (de) | 2004-03-12 | 2004-03-12 | Neue aryl-haltige 5-Acylindolinone, deren Herstellung und deren Verwendung als Arzneimittel |
| DE502005005809T Expired - Fee Related DE502005005809D1 (de) | 2004-03-12 | 2005-03-05 | Neue aryl-haltige 5-acylindolinone, deren herstellung und deren verwendung als arzneimittel |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE502005005809T Expired - Fee Related DE502005005809D1 (de) | 2004-03-12 | 2005-03-05 | Neue aryl-haltige 5-acylindolinone, deren herstellung und deren verwendung als arzneimittel |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US7176231B2 (enExample) |
| EP (1) | EP1727798B1 (enExample) |
| JP (1) | JP2007528882A (enExample) |
| AT (1) | ATE412632T1 (enExample) |
| CA (1) | CA2559115A1 (enExample) |
| DE (2) | DE102004012069A1 (enExample) |
| ES (1) | ES2317201T3 (enExample) |
| WO (1) | WO2005087726A1 (enExample) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0400895D0 (en) * | 2004-01-15 | 2004-02-18 | Smithkline Beecham Corp | Chemical compounds |
| DE102004012068A1 (de) * | 2004-03-12 | 2005-09-29 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue alkyl-haltige 5-Acylindolinone, deren Herstellung und deren Verwendung als Arzneimittel |
| DE102004012070A1 (de) * | 2004-03-12 | 2005-09-29 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue cycloalkyl-haltige 5-Acylindolinone, deren Herstellung und deren Verwendung als Arzneimittel |
| PE20060373A1 (es) * | 2004-06-24 | 2006-04-29 | Smithkline Beecham Corp | Derivados 3-piperidinil-7-carboxamida-indazol como inhibidores de la actividad cinasa de ikk2 |
| US8063071B2 (en) | 2007-10-31 | 2011-11-22 | GlaxoSmithKline, LLC | Chemical compounds |
| ES2446269T3 (es) * | 2006-12-19 | 2014-03-06 | The Board Of Trustees Of The University Of Illinois | 3-Benzofuranil-4-indolil-maleimidas como potentes inhibidores de GSK-3 para trastornos neurodegenerativos |
| AR065804A1 (es) | 2007-03-23 | 2009-07-01 | Smithkline Beecham Corp | Compuesto de indol carboxamida, composicion farmaceutica que lo comprende y uso de dicho compuesto para preparar un medicamento |
| EP2406249A1 (en) | 2009-03-10 | 2012-01-18 | Glaxo Group Limited | Indole derivatives as ikk2 inhibitors |
| US10981896B2 (en) * | 2017-03-02 | 2021-04-20 | Board Of Regents, The University Of Texas System | Indolinone derivatives as inhibitors of maternal embryonic leucine zipper kinase |
| CN108752300B (zh) * | 2018-05-16 | 2022-03-25 | 中国科学院昆明植物研究所 | 苄烯叉苯肽类化合物及其药物组合物和其应用 |
| CN115703758B (zh) * | 2021-08-12 | 2024-03-26 | 中国医学科学院药物研究所 | 一类用作激酶抑制剂的化合物及其制备方法和用途 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9718913D0 (en) * | 1997-09-05 | 1997-11-12 | Glaxo Group Ltd | Substituted oxindole derivatives |
| GB9904933D0 (en) * | 1999-03-04 | 1999-04-28 | Glaxo Group Ltd | Compounds |
| US6498176B1 (en) * | 1999-03-04 | 2002-12-24 | Smithklinebeecham Corporation | 3-(anilinomethylene) oxindoles as protein tyrosine kinase and protein serine/threonine kinase inhibitors |
| CA2432417A1 (fr) * | 2000-12-20 | 2002-06-27 | Societe De Conseils De Recherches Et D'applications Scientifiques (S.C.R .A.S.) | Inhibiteurs de kinases dependantes des cylines (cdk) et de la glycogene synthase kinase-3 (gsk-3) |
| WO2003027109A1 (en) * | 2001-09-27 | 2003-04-03 | Allergan, Inc. | 3-(heteroarylamino)methylene-1, 3-dihydro-2h-indol-2-ones as kinase inhibitors |
-
2004
- 2004-03-12 DE DE102004012069A patent/DE102004012069A1/de not_active Withdrawn
-
2005
- 2005-03-05 DE DE502005005809T patent/DE502005005809D1/de not_active Expired - Fee Related
- 2005-03-05 WO PCT/EP2005/002405 patent/WO2005087726A1/de not_active Ceased
- 2005-03-05 AT AT05715810T patent/ATE412632T1/de not_active IP Right Cessation
- 2005-03-05 CA CA002559115A patent/CA2559115A1/en not_active Abandoned
- 2005-03-05 ES ES05715810T patent/ES2317201T3/es not_active Expired - Lifetime
- 2005-03-05 JP JP2007502260A patent/JP2007528882A/ja active Pending
- 2005-03-05 EP EP05715810A patent/EP1727798B1/de not_active Expired - Lifetime
- 2005-03-10 US US11/077,259 patent/US7176231B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| ES2317201T3 (es) | 2009-04-16 |
| JP2007528882A (ja) | 2007-10-18 |
| EP1727798B1 (de) | 2008-10-29 |
| ATE412632T1 (de) | 2008-11-15 |
| WO2005087726A1 (de) | 2005-09-22 |
| US7176231B2 (en) | 2007-02-13 |
| DE502005005809D1 (de) | 2008-12-11 |
| EP1727798A1 (de) | 2006-12-06 |
| US20050234120A1 (en) | 2005-10-20 |
| CA2559115A1 (en) | 2005-09-22 |
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Effective date: 20110315 |