JP2007528882A - 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 - Google Patents
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 Download PDFInfo
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- JP2007528882A JP2007528882A JP2007502260A JP2007502260A JP2007528882A JP 2007528882 A JP2007528882 A JP 2007528882A JP 2007502260 A JP2007502260 A JP 2007502260A JP 2007502260 A JP2007502260 A JP 2007502260A JP 2007528882 A JP2007528882 A JP 2007528882A
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- Prior art keywords
- group
- alkyl
- amino
- phenyl
- indolinone
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- 125000003118 aryl group Chemical group 0.000 title claims abstract description 8
- 238000002360 preparation method Methods 0.000 title claims description 70
- 239000003814 drug Substances 0.000 title description 4
- 239000000203 mixture Substances 0.000 claims abstract description 39
- 150000003839 salts Chemical class 0.000 claims abstract description 29
- 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 20
- 150000001875 compounds Chemical class 0.000 claims description 72
- -1 nitro , Cyano, amino Chemical group 0.000 claims description 57
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 46
- 125000000217 alkyl group Chemical group 0.000 claims description 28
- 229910052757 nitrogen Inorganic materials 0.000 claims description 28
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 24
- 239000000460 chlorine Substances 0.000 claims description 23
- 125000001424 substituent group Chemical group 0.000 claims description 22
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 20
- 229910052731 fluorine Inorganic materials 0.000 claims description 20
- 229910052801 chlorine Inorganic materials 0.000 claims description 19
- 239000000126 substance Substances 0.000 claims description 19
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 18
- 239000011737 fluorine Substances 0.000 claims description 18
- 125000006698 (C1-C3) dialkylamino group Chemical group 0.000 claims description 16
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 16
- 125000004432 carbon atom Chemical group C* 0.000 claims description 14
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 13
- 125000006597 (C1-C3) alkylcarbonylamino group Chemical group 0.000 claims description 10
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 10
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 10
- 229910052794 bromium Inorganic materials 0.000 claims description 10
- 125000006842 cycloalkyleneimino group Chemical group 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 125000006239 protecting group Chemical group 0.000 claims description 9
- 125000001072 heteroaryl group Chemical group 0.000 claims description 8
- 125000005842 heteroatom Chemical group 0.000 claims description 8
- 125000003277 amino group Chemical group 0.000 claims description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
- 238000006243 chemical reaction Methods 0.000 claims description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
- 208000024827 Alzheimer disease Diseases 0.000 claims description 6
- 125000001246 bromo group Chemical group Br* 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- 206010012601 diabetes mellitus Diseases 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 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
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- 125000002883 imidazolyl group Chemical group 0.000 claims description 5
- 125000001624 naphthyl group Chemical group 0.000 claims description 5
- 125000006563 (C1-3) alkylaminocarbonyl group Chemical group 0.000 claims description 4
- 125000006602 (C1-C3) alkylsulfonylamino group Chemical group 0.000 claims description 4
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- 208000025966 Neurological disease Diseases 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 4
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 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
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- 150000007522 mineralic acids Chemical class 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
- 150000007524 organic acids Chemical class 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 125000004193 piperazinyl group Chemical group 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 208000020925 Bipolar disease Diseases 0.000 claims description 3
- 208000032131 Diabetic Neuropathies Diseases 0.000 claims description 3
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 3
- 150000001412 amines Chemical class 0.000 claims description 3
- 230000003412 degenerative effect Effects 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 3
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 3
- 125000006594 (C1-C3) alkylsulfony group Chemical group 0.000 claims description 2
- 125000006701 (C1-C7) alkyl 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
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 2
- 208000027418 Wounds and injury Diseases 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
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 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
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- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 208000014674 injury Diseases 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
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 2
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 claims 3
- 239000000969 carrier Substances 0.000 claims 2
- 125000006264 diethylaminomethyl group Chemical group [H]C([H])([H])C([H])([H])N(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 claims 1
- 125000006534 ethyl amino methyl group Chemical group [H]N(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 12
- 230000002401 inhibitory effect Effects 0.000 abstract description 4
- 108091007911 GSKs Proteins 0.000 abstract description 3
- 102000004103 Glycogen Synthase Kinases Human genes 0.000 abstract description 3
- 230000009286 beneficial effect Effects 0.000 abstract description 3
- 230000000144 pharmacologic effect Effects 0.000 abstract description 3
- 102000001253 Protein Kinase Human genes 0.000 abstract description 2
- 108060006633 protein kinase Proteins 0.000 abstract description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 201
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 171
- 238000001819 mass spectrum Methods 0.000 description 82
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 57
- 239000000741 silica gel Substances 0.000 description 54
- 229910002027 silica gel Inorganic materials 0.000 description 54
- 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 47
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 33
- 239000013543 active substance Substances 0.000 description 29
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- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 19
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 16
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
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- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 12
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- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 10
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- JYGFTBXVXVMTGB-UHFFFAOYSA-N indolin-2-one Chemical compound C1=CC=C2NC(=O)CC2=C1 JYGFTBXVXVMTGB-UHFFFAOYSA-N 0.000 description 10
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- BQFPCTXLBRVFJL-UHFFFAOYSA-N triethoxymethylbenzene Chemical compound CCOC(OCC)(OCC)C1=CC=CC=C1 BQFPCTXLBRVFJL-UHFFFAOYSA-N 0.000 description 9
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- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 7
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- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- 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
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (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)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Psychiatry (AREA)
- Heart & Thoracic Surgery (AREA)
- Pain & Pain Management (AREA)
- Psychology (AREA)
- Cardiology (AREA)
- Dermatology (AREA)
- Immunology (AREA)
- Rheumatology (AREA)
- Child & Adolescent Psychology (AREA)
- Urology & Nephrology (AREA)
- Hospice & Palliative Care (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| 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 |
| DE102004012069.2 | 2004-03-12 | ||
| PCT/EP2005/002405 WO2005087726A1 (de) | 2004-03-12 | 2005-03-05 | Neue aryl-haltige 5-acylindolinone, deren herstellung und deren verwendung als arzneimittel |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2007528882A true JP2007528882A (ja) | 2007-10-18 |
| JP2007528882A6 JP2007528882A6 (ja) | 2008-02-14 |
| JP2007528882A5 JP2007528882A5 (enExample) | 2008-04-24 |
Family
ID=34895264
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007502260A Pending 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 |
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 |
| PE20081889A1 (es) | 2007-03-23 | 2009-03-05 | Smithkline Beecham Corp | Indol carboxamidas como inhibidores de ikk2 |
| WO2010102968A1 (en) | 2009-03-10 | 2010-09-16 | Glaxo Group Limited | Indole derivatives as ikk2 inhibitors |
| WO2018160967A1 (en) * | 2017-03-02 | 2018-09-07 | 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 |
| WO2002050079A1 (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 AT AT05715810T patent/ATE412632T1/de not_active IP Right Cessation
- 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 EP EP05715810A patent/EP1727798B1/de not_active Expired - Lifetime
- 2005-03-05 JP JP2007502260A patent/JP2007528882A/ja active Pending
- 2005-03-05 CA CA002559115A patent/CA2559115A1/en not_active Abandoned
- 2005-03-05 ES ES05715810T patent/ES2317201T3/es not_active Expired - Lifetime
- 2005-03-10 US US11/077,259 patent/US7176231B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| ES2317201T3 (es) | 2009-04-16 |
| ATE412632T1 (de) | 2008-11-15 |
| EP1727798B1 (de) | 2008-10-29 |
| DE102004012069A1 (de) | 2005-09-29 |
| US7176231B2 (en) | 2007-02-13 |
| DE502005005809D1 (de) | 2008-12-11 |
| EP1727798A1 (de) | 2006-12-06 |
| CA2559115A1 (en) | 2005-09-22 |
| WO2005087726A1 (de) | 2005-09-22 |
| US20050234120A1 (en) | 2005-10-20 |
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