ATE536349T1 - In der 2-stellung durch phenyl substituierte 1h- benzimidazol-4-carbonsäureamide sind wirksame parp-inhibitoren - Google Patents
In der 2-stellung durch phenyl substituierte 1h- benzimidazol-4-carbonsäureamide sind wirksame parp-inhibitorenInfo
- Publication number
- ATE536349T1 ATE536349T1 AT06836157T AT06836157T ATE536349T1 AT E536349 T1 ATE536349 T1 AT E536349T1 AT 06836157 T AT06836157 T AT 06836157T AT 06836157 T AT06836157 T AT 06836157T AT E536349 T1 ATE536349 T1 AT E536349T1
- Authority
- AT
- Austria
- Prior art keywords
- benzimidazole
- phenyl
- carbonic acid
- acid amides
- parp inhibitors
- Prior art date
Links
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- 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
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- 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
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- 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
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- 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
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/02—Antidotes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/18—Benzimidazoles; Hydrogenated benzimidazoles with aryl radicals directly attached in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
-
- 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
- C07D403/10—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 carbon chain containing aromatic rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Oncology (AREA)
- Neurosurgery (AREA)
- Rheumatology (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Communicable Diseases (AREA)
- Cardiology (AREA)
- Physical Education & Sports Medicine (AREA)
- Pain & Pain Management (AREA)
- Obesity (AREA)
- Heart & Thoracic Surgery (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Psychology (AREA)
- Urology & Nephrology (AREA)
- Virology (AREA)
- Toxicology (AREA)
- Vascular Medicine (AREA)
- Dermatology (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US72168305P | 2005-09-29 | 2005-09-29 | |
PCT/US2006/038169 WO2007041357A1 (en) | 2005-09-29 | 2006-09-28 | 1h-benzimidazole-4-carboxamides substituted with phenyl at the 2-position are potent parp inhibitors |
Publications (1)
Publication Number | Publication Date |
---|---|
ATE536349T1 true ATE536349T1 (de) | 2011-12-15 |
Family
ID=37692513
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
AT06836157T ATE536349T1 (de) | 2005-09-29 | 2006-09-28 | In der 2-stellung durch phenyl substituierte 1h- benzimidazol-4-carbonsäureamide sind wirksame parp-inhibitoren |
Country Status (8)
Country | Link |
---|---|
US (2) | US8697736B2 (de) |
EP (1) | EP1957477B1 (de) |
JP (1) | JP5227796B2 (de) |
CN (1) | CN101316834A (de) |
AT (1) | ATE536349T1 (de) |
CA (1) | CA2623822C (de) |
ES (1) | ES2378692T3 (de) |
WO (1) | WO2007041357A1 (de) |
Families Citing this family (30)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1391457B1 (de) | 1998-11-03 | 2013-12-25 | AbbVie Deutschland GmbH & Co KG | Substituierte 2-Phenylbenzimidazole und deren Verwendung als PARP Inhibitoren |
US7728026B2 (en) * | 2005-04-11 | 2010-06-01 | Abbott Laboratories, Inc. | 2-substituted-1 h-benzimidazile-4-carboxamides are PARP inhibitors |
CN101309908A (zh) * | 2005-11-15 | 2008-11-19 | 艾博特公司 | 作为有效parp抑制剂的取代的1h-苯并咪唑-4-甲酰胺化合物 |
EP2007733B1 (de) * | 2006-04-03 | 2016-05-25 | MSD Italia S.r.l. | Amidsubstituierte indazol- und benzotriazolderivate als inhibitoren der poly(adp-ribose)polymerase (parp) |
MX2008014004A (es) * | 2006-05-02 | 2008-11-12 | Abbott Lab | 1h-benzimidazol-4-carboxamidas sustituidas son inhibidores de parp potentes. |
JP4611444B2 (ja) * | 2007-01-10 | 2011-01-12 | イステイチユート・デイ・リチエルケ・デイ・ビオロジア・モレコラーレ・ピ・アンジエレツテイ・エツセ・ピー・アー | ポリ(adp−リボース)ポリメラーゼ(parp)阻害剤としてのアミド置換インダゾール |
US8067613B2 (en) * | 2007-07-16 | 2011-11-29 | Abbott Laboratories | Benzimidazole poly(ADP ribose)polymerase inhibitors |
JP2011503111A (ja) * | 2007-11-12 | 2011-01-27 | バイパー サイエンシズ,インコーポレイティド | Parp阻害剤単独又は抗腫瘍剤との組み合わせによる乳がんの治療 |
KR101653548B1 (ko) | 2008-01-08 | 2016-09-02 | 머크 샤프 앤드 돔 리미티드 | 2-{4-[(3s)-피페리딘-3-일]페닐}-2h-인다졸-7-카복스아미드의 약제학적으로 허용되는 염 |
CN101998959B (zh) | 2008-02-06 | 2013-08-28 | 生物马林药物股份有限公司 | 聚(adp-核糖)聚合酶(parp)的苯并噁唑甲酰胺抑制剂 |
WO2010083199A1 (en) * | 2009-01-19 | 2010-07-22 | Abbott Laboratories | Benzthiazole inhibitors of poly(adp-ribose)polymerase |
ES2882797T3 (es) * | 2009-04-02 | 2021-12-02 | Merck Serono Sa | Inhibidores de dihidroorotato deshidrogenasa |
WO2011006803A1 (en) * | 2009-07-14 | 2011-01-20 | Nerviano Medical Sciences S.R.L. | 3-0x0-2, 3, -dihydro-lh-isoindole-4-carboxamides with selective parp-1 inhibition |
ES2759751T3 (es) * | 2009-07-14 | 2020-05-12 | Nerviano Medical Sciences Srl | 3-oxo-2,3-dihidro-1H-isoindol-4-carboxamidas |
CA2798697A1 (en) | 2010-05-10 | 2011-11-17 | Radikal Therapeutics Inc. | Lipoic acid and nitroxide derivatives and uses thereof |
ES2616464T3 (es) | 2011-07-26 | 2017-06-13 | Nerviano Medical Sciences S.R.L. | Derivados de 3-Oxo-2,3-dihidro-1H-indazol-4-carboxamida como inhibidores de PARP-1 |
MX348338B (es) | 2012-10-15 | 2017-06-07 | Albemarle Corp | Procesos para la síntesis de 2-amino-4, 6-dimetoxibenzamida y otros compuestos de benzamida. |
CN102964354B (zh) * | 2012-11-16 | 2014-08-13 | 江苏先声药业有限公司 | 一类噻吩并咪唑衍生物及其应用 |
KR101896567B1 (ko) | 2015-07-23 | 2018-09-07 | 인스티튜트 큐리 | 암 치료를 위한 디베이트 분자와 parp 억제제의 병용 용도 |
GB201519573D0 (en) | 2015-11-05 | 2015-12-23 | King S College London | Combination |
JP6590226B2 (ja) * | 2016-05-11 | 2019-10-16 | 株式会社シード探索研究所 | オキサアジリジン化合物およびその製造方法 |
WO2018162439A1 (en) | 2017-03-08 | 2018-09-13 | Onxeo | New predictive biomarker for the sensitivity to a treatment of cancer with a dbait molecule |
JP7356450B2 (ja) | 2018-01-05 | 2023-10-04 | サイブレクサ 1・インコーポレイテッド | 酸性または低酸素の疾患組織を含む疾患の治療のための化合物、組成物、及び方法 |
CA3092779A1 (en) | 2018-03-13 | 2019-09-19 | Onxeo | A dbait molecule against acquired resistance in the treatment of cancer |
WO2020252383A2 (en) * | 2019-06-14 | 2020-12-17 | Srx Cardio, Llc | Compounds for the modulation of proprotein convertase subtilisin/kexin type 9 (pcsk9) |
AU2020309570A1 (en) | 2019-07-10 | 2022-02-03 | Cybrexa 2, Inc. | Peptide conjugates of cytotoxins as therapeutics |
JP2022541747A (ja) | 2019-07-10 | 2022-09-27 | サイブレクサ 3,インコーポレイテッド | 治療薬としての微小管標的化剤のペプチドコンジュゲート |
WO2021148581A1 (en) | 2020-01-22 | 2021-07-29 | Onxeo | Novel dbait molecule and its use |
AU2022206297A1 (en) | 2021-01-08 | 2023-08-03 | Cybrexa 2, Inc. | Process for preparing a conjugate linking moiety |
WO2022155172A1 (en) | 2021-01-13 | 2022-07-21 | Cybrexa 3, Inc. | Peptide conjugates of therapeutics |
Family Cites Families (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4093726A (en) * | 1976-12-02 | 1978-06-06 | Abbott Laboratories | N-(2-benzimidazolyl)-piperazines |
US6911462B2 (en) * | 1998-05-22 | 2005-06-28 | Avanir Pharmaceuticals | Benzimidazole compounds for regulating IgE |
GB9815880D0 (en) * | 1998-07-21 | 1998-09-16 | Pfizer Ltd | Heterocycles |
EP1391457B1 (de) * | 1998-11-03 | 2013-12-25 | AbbVie Deutschland GmbH & Co KG | Substituierte 2-Phenylbenzimidazole und deren Verwendung als PARP Inhibitoren |
ID28846A (id) | 1998-11-17 | 2001-07-05 | Basf Ag | 2-fenilbenzimidazol dan 2_fenilindol, pembuatan dan penggunaanya |
TR200101498T2 (tr) * | 1998-11-27 | 2001-11-21 | Basf Aktiengesellschaft | İkameli benzimidazoller ve parp inhibitörleri olarak kullanımları |
DE19918211A1 (de) | 1999-04-22 | 2000-10-26 | Basf Ag | Cycloalkylsubstituierte Benzimidazole, deren Herstellung und Anwendung |
DE19920936A1 (de) * | 1999-05-07 | 2000-11-09 | Basf Ag | Heterozyklisch substituierte Benzimidazole, deren Herstellung und Anwendung |
DE10021468A1 (de) * | 2000-05-04 | 2001-11-08 | Basf Ag | Verwendung von PARP-Inhibitoren in kosmetischen Zubereitungen |
US7122679B2 (en) * | 2000-05-09 | 2006-10-17 | Cephalon, Inc. | Multicyclic compounds and the use thereof |
HU0301154D0 (en) * | 2003-04-28 | 2003-07-28 | Hideg Kalman Dr | Pharmaceutical composition |
TWI375673B (en) | 2005-04-11 | 2012-11-01 | Abbott Lab | 1h-benzimidazole-4-carboxamides substituted with a quaternary carbon at the 2-position are potent parp inhibitors |
US7728026B2 (en) * | 2005-04-11 | 2010-06-01 | Abbott Laboratories, Inc. | 2-substituted-1 h-benzimidazile-4-carboxamides are PARP inhibitors |
CN101309908A (zh) * | 2005-11-15 | 2008-11-19 | 艾博特公司 | 作为有效parp抑制剂的取代的1h-苯并咪唑-4-甲酰胺化合物 |
SI2338487T1 (sl) * | 2006-01-17 | 2014-01-31 | Abbott Laboratories | Kombinacijska terapija z inhibitorji PARP |
MX2008014004A (es) * | 2006-05-02 | 2008-11-12 | Abbott Lab | 1h-benzimidazol-4-carboxamidas sustituidas son inhibidores de parp potentes. |
US8067613B2 (en) * | 2007-07-16 | 2011-11-29 | Abbott Laboratories | Benzimidazole poly(ADP ribose)polymerase inhibitors |
-
2006
- 2006-09-28 EP EP06836157A patent/EP1957477B1/de active Active
- 2006-09-28 ES ES06836157T patent/ES2378692T3/es active Active
- 2006-09-28 JP JP2008533692A patent/JP5227796B2/ja not_active Expired - Fee Related
- 2006-09-28 WO PCT/US2006/038169 patent/WO2007041357A1/en active Application Filing
- 2006-09-28 CN CNA2006800443709A patent/CN101316834A/zh active Pending
- 2006-09-28 CA CA2623822A patent/CA2623822C/en not_active Expired - Fee Related
- 2006-09-28 AT AT06836157T patent/ATE536349T1/de active
- 2006-09-29 US US11/536,994 patent/US8697736B2/en active Active
-
2014
- 2014-04-11 US US14/250,698 patent/US20140296235A1/en not_active Abandoned
Also Published As
Publication number | Publication date |
---|---|
CA2623822A1 (en) | 2007-04-12 |
JP5227796B2 (ja) | 2013-07-03 |
ES2378692T3 (es) | 2012-04-17 |
US8697736B2 (en) | 2014-04-15 |
CN101316834A (zh) | 2008-12-03 |
US20070179136A1 (en) | 2007-08-02 |
US20140296235A1 (en) | 2014-10-02 |
CA2623822C (en) | 2013-11-12 |
EP1957477B1 (de) | 2011-12-07 |
JP2009510106A (ja) | 2009-03-12 |
WO2007041357A1 (en) | 2007-04-12 |
EP1957477A1 (de) | 2008-08-20 |
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