EA200300982A1 - Гетероциклические производные для лечения рака и других пролиферативных заболеваний - Google Patents
Гетероциклические производные для лечения рака и других пролиферативных заболеванийInfo
- Publication number
- EA200300982A1 EA200300982A1 EA200300982A EA200300982A EA200300982A1 EA 200300982 A1 EA200300982 A1 EA 200300982A1 EA 200300982 A EA200300982 A EA 200300982A EA 200300982 A EA200300982 A EA 200300982A EA 200300982 A1 EA200300982 A1 EA 200300982A1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- substituted
- aryl
- heteroaryl
- alkyl
- cancer
- Prior art date
Links
- 206010028980 Neoplasm Diseases 0.000 title abstract 2
- 201000011510 cancer Diseases 0.000 title abstract 2
- 201000010099 disease Diseases 0.000 title abstract 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title abstract 2
- 230000002062 proliferating effect Effects 0.000 title 1
- 125000001072 heteroaryl group Chemical group 0.000 abstract 6
- 125000003118 aryl group Chemical group 0.000 abstract 3
- 125000003107 substituted aryl group Chemical group 0.000 abstract 3
- 125000000217 alkyl group Chemical group 0.000 abstract 2
- 125000000623 heterocyclic group Chemical group 0.000 abstract 2
- 125000000547 substituted alkyl group Chemical group 0.000 abstract 2
- 125000000753 cycloalkyl group Chemical group 0.000 abstract 1
- 150000002391 heterocyclic compounds Chemical class 0.000 abstract 1
- 229910052739 hydrogen Inorganic materials 0.000 abstract 1
- 239000001257 hydrogen Substances 0.000 abstract 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 abstract 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
- 125000005346 substituted cycloalkyl group Chemical group 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/34—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US27475101P | 2001-03-07 | 2001-03-07 | |
| PCT/US2002/007001 WO2002072009A2 (en) | 2001-03-07 | 2002-03-07 | Heterocyclic derivatives for the treatment of cancer and other proliferative diseases |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EA200300982A1 true EA200300982A1 (ru) | 2004-12-30 |
Family
ID=23049469
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA200300982A EA200300982A1 (ru) | 2001-03-07 | 2002-03-07 | Гетероциклические производные для лечения рака и других пролиферативных заболеваний |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US7153875B2 (https=) |
| EP (1) | EP1385465A4 (https=) |
| JP (1) | JP2005506290A (https=) |
| AU (1) | AU2002252227A1 (https=) |
| BR (1) | BR0207846A (https=) |
| CA (1) | CA2440184A1 (https=) |
| EA (1) | EA200300982A1 (https=) |
| IL (1) | IL157740A0 (https=) |
| MX (1) | MXPA03008117A (https=) |
| NO (1) | NO20033883L (https=) |
| PL (1) | PL373912A1 (https=) |
| WO (1) | WO2002072009A2 (https=) |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ517993A (en) | 1999-08-31 | 2004-03-26 | Incyte San Diego Inc | Benzylidene-thiazolidinediones and analogues and their use in the treatment of diabetes |
| IL157740A0 (en) | 2001-03-07 | 2004-03-28 | Incyte San Diego Inc | Heterocyclic derivatives and pharmaceutical compositions containing the same |
| US7265139B2 (en) * | 2001-03-08 | 2007-09-04 | Incyte San Diego Inc. | RXR activating molecules |
| WO2003016267A1 (en) * | 2001-08-17 | 2003-02-27 | Incyte San Diego Incorporated | Oxime derivatives for the treatment of dyslipidemia and hypercholesteremia |
| AU2002352706A1 (en) * | 2001-11-15 | 2003-06-10 | Maxia Pharmaceuticals, Inc. | N-substituted heterocycles for the treatment of hypercholesteremia, dyslipidemia and other metabolic disorders, cancer, and other diseases |
| EP1456165A1 (en) | 2001-11-30 | 2004-09-15 | The Burnham Institute | Induction of apoptosis in cancer cells |
| US7102000B2 (en) * | 2002-03-08 | 2006-09-05 | Incyte San Diego Inc. | Heterocyclic amide derivatives for the treatment of diabetes and other diseases |
| US7196108B2 (en) * | 2002-03-08 | 2007-03-27 | Incyte San Diego Inc. | Bicyclic heterocycles for the treatment of diabetes and other diseases |
| WO2004094409A1 (en) * | 2003-03-27 | 2004-11-04 | Lankenau Institute For Medical Research | Novel ido inhibitors and methods of use |
| FR2856401B1 (fr) * | 2003-06-20 | 2010-02-12 | Galderma Res & Dev | Nouveaux composes modulateurs des recepteurs de type ppargamma et leur utilisation dans des compositions cosmetiques ou pharmaceutiques |
| DE10351744A1 (de) * | 2003-10-31 | 2005-06-16 | Schering Ag | Thiazolidinone, deren Herstellung und Verwendung als Arzneimittel |
| US7122700B2 (en) | 2004-07-30 | 2006-10-17 | Xerox Corporation | Arylamine processes |
| JP5155148B2 (ja) * | 2005-04-08 | 2013-02-27 | ガルデルマ・リサーチ・アンド・デヴェロップメント | ６−［３−（１−アダマンチル）−４−メトキシフェニル］−２−ナフトエ酸の合成方法 |
| FR2884248B1 (fr) * | 2005-04-08 | 2007-05-18 | Galderma Res & Dev | Nouveau procede de preparation de l'acide 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphtoique |
| KR100814109B1 (ko) * | 2006-01-09 | 2008-03-14 | 한국생명공학연구원 | 로다닌 유도체, 이의 제조방법 및 이를 유효성분으로함유하는 약학적 조성물 |
| TW200815429A (en) * | 2006-04-11 | 2008-04-01 | Smithkline Beecham Corp | Thiazolidinedione derivatives as PI3 kinase inhibitors |
| US20080255115A1 (en) * | 2007-04-11 | 2008-10-16 | Michael Gerard Darcy | Thiazolidinedione derivatives as pi3 kinase inhibitors |
| PE20090288A1 (es) * | 2007-05-10 | 2009-04-03 | Smithkline Beecham Corp | Derivados de quinoxalina como inhibidores de la pi3 quinasa |
| PE20090717A1 (es) * | 2007-05-18 | 2009-07-18 | Smithkline Beecham Corp | Derivados de quinolina como inhibidores de la pi3 quinasa |
| KR20100098653A (ko) | 2007-11-21 | 2010-09-08 | 디코드 제네틱스 이에이치에프 | 염증의 치료를 위한 바이아릴 ｐｄｅ４ 억제제 |
| CA2722582A1 (en) * | 2007-11-21 | 2009-05-28 | Decode Genetics Ehf. | Biaryl pde4 inhibitors for treating inflammation |
| CN102558088A (zh) * | 2010-12-31 | 2012-07-11 | 中国科学院上海药物研究所 | 联苯亚甲基-2-硫代-4-噻唑酮类化合物及其制备方法和用途 |
| EP4455143A4 (en) * | 2021-12-21 | 2025-10-29 | Medific Inc | THIAZOLIDINEDIONE DERIVATIVE COMPOUND AND PHARMACEUTICAL COMPOSITION FOR PREVENTING OR TREATMENT OF CANCER INCLUDING IT |
| KR102922092B1 (ko) * | 2021-12-21 | 2026-02-03 | 주식회사 메디픽바이오 | 치환된 티아졸리딘디온 유도체 화합물 및 이를 포함하는 암의 예방 또는 치료용 약학적 조성물 |
| US12115148B1 (en) | 2024-05-10 | 2024-10-15 | Imam Mohammad Ibn Saud Islamic University | 3-(2-(1,3-dioxoisoindolin-2-yl)ethyl)-5-(2-hydroxy-5-nitrobenzylidene)thiazolidine-2,4-dione as a potential antitumor and apoptotic inducer |
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| US4051842A (en) | 1975-09-15 | 1977-10-04 | International Medical Corporation | Electrode and interfacing pad for electrical physiological systems |
| DE2626348C3 (de) | 1976-06-11 | 1980-01-31 | Siemens Ag, 1000 Berlin Und 8000 Muenchen | Implantierbare Dosiereinrichtung |
| JPS5538359A (en) | 1978-09-12 | 1980-03-17 | Hamari Yakuhin Kogyo Kk | Preparation of 2-(3-benzoylphenyl)-propionic acid |
| US4383529A (en) | 1980-11-03 | 1983-05-17 | Wescor, Inc. | Iontophoretic electrode device, method and gel insert |
| IL72684A (en) | 1984-08-14 | 1989-02-28 | Israel State | Pharmaceutical compositions for controlled transdermal delivery of cholinergic or anticholinergic basic drugs |
| US4713244A (en) | 1985-08-16 | 1987-12-15 | Bausch & Lomb Incorporated | Sustained-release formulation containing an amino acid polymer with a lower alkyl (C1 -C4) polar solvent |
| US4931279A (en) | 1985-08-16 | 1990-06-05 | Bausch & Lomb Incorporated | Sustained release formulation containing an ion-exchange resin |
| US4668506A (en) | 1985-08-16 | 1987-05-26 | Bausch & Lomb Incorporated | Sustained-release formulation containing and amino acid polymer |
| CA1325222C (en) | 1985-08-23 | 1993-12-14 | Lederle (Japan), Ltd. | Process for producing 4-biphenylylacetic acid |
| JP2539504B2 (ja) | 1987-03-11 | 1996-10-02 | 鐘淵化学工業株式会社 | ヒドロキシスチレン誘導体 |
| FI91869C (fi) * | 1987-03-18 | 1994-08-25 | Tanabe Seiyaku Co | Menetelmä antidiabeettisena aineena käytettävien bensoksatsolijohdannaisten valmistamiseksi |
| US5223522A (en) | 1988-03-08 | 1993-06-29 | Pfizer Inc. | Thiazolidinedione hypoglycemic agents |
| US5330998A (en) | 1988-03-08 | 1994-07-19 | Pfizer Inc. | Thiazolidinedione derivatives as hypoglycemic agents |
| IE62214B1 (en) | 1988-05-25 | 1995-01-11 | Warner Lambert Co | Arylmethylenyl derivatives of thiazolidinones, imidazolidinones and oxazolidinones useful as antiallergy agents and antiinflammatory agents |
| ATE173728T1 (de) | 1991-07-22 | 1998-12-15 | Pfizer | Verfahren zur herstellung von (s)-4-(3-(5-methyl- 2-phenyl-4-oxazolyl)- 1-hydroxypropyl> brombenzol |
| DE10199033I2 (de) | 1992-04-22 | 2003-01-09 | Ligand Parmaceuticals Inc | Retinoid-x Rezeptor selektive Verbindungen |
| US5780676A (en) | 1992-04-22 | 1998-07-14 | Ligand Pharmaceuticals Incorporated | Compounds having selective activity for Retinoid X Receptors, and means for modulation of processes mediated by Retinoid X Receptors |
| EP0915090A1 (en) | 1992-09-10 | 1999-05-12 | Eli Lilly And Company | Compounds useful as hypoglycemic agents and for treating Alzheimer's disease |
| JPH08506323A (ja) | 1992-11-25 | 1996-07-09 | ラ ホヤ キャンサー リサーチ ファウンデーション | Ｒｘｒホモダイマー形成ならびに架橋二環式芳香族化合物および調節遺伝子発現におけるそれらの使用 |
| AU692839B2 (en) | 1994-02-17 | 1998-06-18 | American Home Products Corporation | Substituted biphenyl derivatives as phosphodiesterase inhibitors |
| US5691376A (en) | 1994-02-17 | 1997-11-25 | American Home Products Corporation | Substituted biphenyl derivatives |
| JPH09136877A (ja) | 1995-06-16 | 1997-05-27 | Takeda Chem Ind Ltd | 複素環化合物、その製造法及び用途 |
| EP0850067A4 (en) | 1995-07-17 | 1999-12-15 | Cird Galderma | METHODS OF TREATING CANCER USING 6- 3- 1-ADAMANTYL] -4-HYDROXYPHENYL] |
| EP0844997A1 (en) | 1996-06-19 | 1998-06-03 | Dr. Reddy's Research Foundation | Novel polymorphic forms of troglitazone having enhanced anti-diabetic activity and a process for their preparation |
| IL127946A0 (en) | 1996-07-08 | 2000-02-17 | Cird Galderma | Apoptosis inducing adamantyl derivatives and their usage as anti-cancer agents |
| WO1999009965A2 (en) | 1997-08-21 | 1999-03-04 | Takeda Chemical Industries, Ltd. | Anti-inflammatory agent |
| US5972986A (en) * | 1997-10-14 | 1999-10-26 | G.D. Searle & Co. | Method of using cyclooxygenase-2 inhibitors in the treatment and prevention of neoplasia |
| JP4398585B2 (ja) | 1997-11-12 | 2010-01-13 | 有限会社ケムフィズ | レチノイドレセプター作用剤 |
| US6262044B1 (en) * | 1998-03-12 | 2001-07-17 | Novo Nordisk A/S | Modulators of protein tyrosine phosphatases (PTPASES) |
| US6331633B1 (en) | 1998-05-08 | 2001-12-18 | Calyx Therapeutics Inc. | Heterocyclic analogs of diphenylethylene compounds |
| ID27787A (id) | 1998-08-21 | 2001-04-26 | Viro Pharma Inc | Senyawa, komposisi dan metode untuk pengobatan atau pencegahan infeksi yang disebabkan oleh virus dan penyakit-penyakit yang berkaitan |
| WO2000018748A1 (en) | 1998-09-30 | 2000-04-06 | Roche Diagnostics Gmbh | Rhodanine derivatives for the treatment and prevention of metabolic bone disorders |
| WO2000032598A1 (en) | 1998-12-04 | 2000-06-08 | Structural Bioinformatics Inc. | Methods and compositions for treating inflammatory diseases utilizing inhibitors of tumor necrosis factor activity |
| WO2000063196A1 (en) | 1999-04-20 | 2000-10-26 | Novo Nordisk A/S | New compounds, their preparation and use |
| US6462032B1 (en) | 1999-05-04 | 2002-10-08 | Wyeth | Cyclic regimens utilizing indoline derivatives |
| NZ517993A (en) | 1999-08-31 | 2004-03-26 | Incyte San Diego Inc | Benzylidene-thiazolidinediones and analogues and their use in the treatment of diabetes |
| KR100608416B1 (ko) | 1999-11-12 | 2006-08-02 | 후지모토 쿄다이 가부시키가이샤 | 2-(ｎ-시아노이미노)티아졸리딘-4-온 유도체 |
| FR2812876B1 (fr) | 2000-08-08 | 2002-09-27 | Galderma Res & Dev | Nouveaux composes bi-aromatiques activateurs des recepteurs de type ppar-gamma et leur utilisation dans des compositions cosmetiques ou pharmaceutiques |
| IL157740A0 (en) | 2001-03-07 | 2004-03-28 | Incyte San Diego Inc | Heterocyclic derivatives and pharmaceutical compositions containing the same |
| US7265139B2 (en) * | 2001-03-08 | 2007-09-04 | Incyte San Diego Inc. | RXR activating molecules |
| EP1373240B1 (en) | 2001-03-14 | 2005-06-15 | Eli Lilly And Company | Retinoid x receptor modulators |
| JP4590158B2 (ja) | 2001-04-04 | 2010-12-01 | オーソ−マクニール・フアーマシユーチカル・インコーポレーテツド | グルコース再吸収阻害剤およびレチノイド−ｘ受容体モジュレーターを含んで成る併用療法 |
| WO2003016267A1 (en) * | 2001-08-17 | 2003-02-27 | Incyte San Diego Incorporated | Oxime derivatives for the treatment of dyslipidemia and hypercholesteremia |
| AU2002352706A1 (en) * | 2001-11-15 | 2003-06-10 | Maxia Pharmaceuticals, Inc. | N-substituted heterocycles for the treatment of hypercholesteremia, dyslipidemia and other metabolic disorders, cancer, and other diseases |
| TW200304375A (en) * | 2001-12-06 | 2003-10-01 | Maxia Pharmaceuticals Inc | 2-Substituted thiazolidinone and oxazolidinone derivatives for the inhibition of phosphatases and the treatment of cancer |
| US7102000B2 (en) * | 2002-03-08 | 2006-09-05 | Incyte San Diego Inc. | Heterocyclic amide derivatives for the treatment of diabetes and other diseases |
| US7196108B2 (en) * | 2002-03-08 | 2007-03-27 | Incyte San Diego Inc. | Bicyclic heterocycles for the treatment of diabetes and other diseases |
| CA2529154C (en) * | 2003-06-20 | 2013-05-07 | Galderma Research & Development, S.N.C. | Novel compounds that modulate ppar.gamma. type receptors, and use thereof in cosmetic or pharmaceutical compositions |
-
2002
- 2002-03-07 IL IL15774002A patent/IL157740A0/xx unknown
- 2002-03-07 PL PL02373912A patent/PL373912A1/xx not_active Application Discontinuation
- 2002-03-07 AU AU2002252227A patent/AU2002252227A1/en not_active Abandoned
- 2002-03-07 US US10/094,142 patent/US7153875B2/en not_active Expired - Fee Related
- 2002-03-07 WO PCT/US2002/007001 patent/WO2002072009A2/en not_active Ceased
- 2002-03-07 BR BR0207846-5A patent/BR0207846A/pt not_active Application Discontinuation
- 2002-03-07 JP JP2002570969A patent/JP2005506290A/ja active Pending
- 2002-03-07 EA EA200300982A patent/EA200300982A1/ru unknown
- 2002-03-07 MX MXPA03008117A patent/MXPA03008117A/es unknown
- 2002-03-07 CA CA002440184A patent/CA2440184A1/en not_active Abandoned
- 2002-03-07 EP EP02721289A patent/EP1385465A4/en not_active Withdrawn
-
2003
- 2003-09-02 NO NO20033883A patent/NO20033883L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| CA2440184A1 (en) | 2002-09-19 |
| WO2002072009A3 (en) | 2003-10-16 |
| NO20033883L (no) | 2003-11-05 |
| PL373912A1 (en) | 2005-09-19 |
| EP1385465A2 (en) | 2004-02-04 |
| EP1385465A4 (en) | 2005-09-07 |
| JP2005506290A (ja) | 2005-03-03 |
| MXPA03008117A (es) | 2004-11-12 |
| US7153875B2 (en) | 2006-12-26 |
| AU2002252227A1 (en) | 2002-09-24 |
| WO2002072009A2 (en) | 2002-09-19 |
| US20020143182A1 (en) | 2002-10-03 |
| BR0207846A (pt) | 2005-09-13 |
| IL157740A0 (en) | 2004-03-28 |
| NO20033883D0 (no) | 2003-09-02 |
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