ZA200200502B - Methods for treating or preventing pain and anxiety. - Google Patents
Methods for treating or preventing pain and anxiety. Download PDFInfo
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- ZA200200502B ZA200200502B ZA200200502A ZA200200502A ZA200200502B ZA 200200502 B ZA200200502 B ZA 200200502B ZA 200200502 A ZA200200502 A ZA 200200502A ZA 200200502 A ZA200200502 A ZA 200200502A ZA 200200502 B ZA200200502 B ZA 200200502B
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Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/72—Nitrogen atoms
- C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- 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
- C07D401/12—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 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
- C07D405/12—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 chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- C07D417/12—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 chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
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- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
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- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Ophthalmology & Optometry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Hydrogenated Pyridines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (1)
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| US14722199P | 1999-08-04 | 1999-08-04 |
Publications (1)
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| ZA200200502B true ZA200200502B (en) | 2003-04-30 |
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| EP (1) | EP1208085B1 (de) |
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| AU (1) | AU779034B2 (de) |
| CA (1) | CA2378241A1 (de) |
| DE (2) | DE60037321D1 (de) |
| NZ (1) | NZ516610A (de) |
| WO (1) | WO2001010380A2 (de) |
| ZA (1) | ZA200200502B (de) |
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| NZ527771A (en) * | 1999-08-04 | 2005-04-29 | Icagen Inc | Methods for treating or preventing anxiety |
| US6495550B2 (en) * | 1999-08-04 | 2002-12-17 | Icagen, Inc. | Pyridine-substituted benzanilides as potassium ion channel openers |
| AU2002238023B2 (en) * | 1999-08-04 | 2008-03-13 | Icagen, Inc | Pyridine-substituted benzanilides as potassium ion channel openers |
| ATE380176T1 (de) | 1999-08-04 | 2007-12-15 | Icagen Inc | Benzanilide als öffner des kaliumkanals |
| US6589986B2 (en) | 2000-12-20 | 2003-07-08 | Wyeth | Methods of treating anxiety disorders |
| CA2438868A1 (en) * | 2001-02-20 | 2002-09-19 | Valentin K. Gribkoff | Modulators of kcnq potassium channels and use thereof in treating migraine and mechanistically related diseases |
| JP2004531483A (ja) * | 2001-02-20 | 2004-10-14 | ブリストル−マイヤーズ スクイブ カンパニー | Ｋｃｎｑカリウムチャネルのモジュレーターとしてのフルオロオキシンドール誘導体 |
| CA2448894A1 (en) | 2001-05-31 | 2002-12-05 | Bristol-Myers Squibb Company | Cinnamide derivatives as kcnq potassium channel modulators |
| US7205307B2 (en) * | 2002-02-14 | 2007-04-17 | Icagen, Inc. | Pyrimidines as novel openers of potassium ion channels |
| US7442519B2 (en) * | 2002-06-25 | 2008-10-28 | Serono Genetics Institute, S.A. | KCNQ2-15 potassium channel |
| EP1537237A2 (de) * | 2002-06-25 | 2005-06-08 | Genset S.A. | Verwendung von modulatoren der pp2a phosphatase zur behandlung von mentalen erkrankungen |
| AU2003295782A1 (en) | 2002-11-22 | 2004-06-18 | Bristol-Myers Squibb Company | Pyridinyl, pyrimidinyl and pyrazinyl amides as potassium channel openers |
| EP1581516A4 (de) | 2002-11-22 | 2007-10-17 | Bristol Myers Squibb Co | 3-heterocyclylbenzylamidderivate als kaliumkanalöffner |
| AU2003295781A1 (en) | 2002-11-22 | 2004-06-18 | Bristol-Myers Squibb Company | Arylcyclopropylcarboxylic amides as potassium channel openers |
| WO2004047745A2 (en) * | 2002-11-22 | 2004-06-10 | Bristol-Myers Squibb Company | 3-(pyridinyl-piperazin-1-yl)-phenylethyl amides as potassium channel openers |
| AU2003294441A1 (en) | 2002-11-22 | 2004-06-18 | Bristol-Myers Squibb Company | 1-aryl-2-hydroxyethyl amides as potassium channel openers |
| EP1603858A2 (de) * | 2003-03-11 | 2005-12-14 | NeuroSearch A/S | Kncq-kanal-modulatoren und ihre pharmazeutische verwendung |
| EP1680109A4 (de) | 2003-10-07 | 2009-05-06 | Renovis Inc | Amid-derivate als ionenkanal-liganden und pharmazeutische zusammensetzungen und anwendungsverfahren |
| US20050089559A1 (en) * | 2003-10-23 | 2005-04-28 | Istvan Szelenyi | Combinations of potassium channel openers and sodium channel inhibitors or sodium channel-influencing active compounds for treating pains |
| CA2571717A1 (en) * | 2004-06-23 | 2006-01-05 | Josette-Nicole Mahy Gehenne | Compounds for the treatment of inflammation of the central nervous system |
| UA89503C2 (uk) * | 2004-09-13 | 2010-02-10 | Х. Луннбек А/С | Заміщені похідні аніліну |
| KR20070092297A (ko) * | 2004-12-21 | 2007-09-12 | 데브젠 엔브이 | Ｋｖ4 이온 채널 활성을 갖는 화합물 |
| US7576099B2 (en) | 2005-02-28 | 2009-08-18 | Renovis, Inc. | Amide derivatives as ion-channel ligands and pharmaceutical compositions and methods of using the same |
| CA2599890C (en) * | 2005-03-03 | 2011-05-03 | H. Lundbeck A/S | Substituted pyridine derivatives |
| UA92340C2 (en) * | 2005-03-03 | 2010-10-25 | Х. Луннбек А/С | Substituted pyridine derivatives |
| US7960436B2 (en) * | 2006-06-05 | 2011-06-14 | Valeant Pharmaceuticals International | Substituted arylamino-1,2,3,4-tetrahydro naphthalenes and-2,3-dihydro-1H-indenes as potassium channel modulators |
| US20080045534A1 (en) * | 2006-08-18 | 2008-02-21 | Valeant Pharmaceuticals North America | Derivatives of 1,3-diamino benzene as potassium channel modulators |
| CN101563085A (zh) * | 2006-08-23 | 2009-10-21 | 威朗国际制药公司 | 作为钾通道调节剂的4-(n-氮杂环烷基)酰苯胺的衍生物 |
| US8993593B2 (en) * | 2006-08-23 | 2015-03-31 | Valeant Pharmaceuticals International | N-(4-(6-fluoro-3,4-dihydroisoquinolin-2(1H)-yl)-2,6-dimethylphenyl)-3,3-dimethylbutanamide as potassium channel modulators |
| US8722929B2 (en) * | 2006-10-10 | 2014-05-13 | Valeant Pharmaceuticals International | N-[2-amino-4-(phenylmethoxy)phenyl] amides and related compounds as potassium channel modulators |
| AU2007325629A1 (en) * | 2006-11-28 | 2008-06-05 | Valeant Pharmaceuticals International | 1,4 diamino bicyclic retigabine analogues as potassium channel modulators |
| US8093265B2 (en) | 2007-03-09 | 2012-01-10 | Renovis, Inc. | Bicycloheteroaryl compounds as P2X7 modulators and uses thereof |
| US8367684B2 (en) * | 2007-06-13 | 2013-02-05 | Valeant Pharmaceuticals International | Derivatives of 4-(N-azacycloalkyl) anilides as potassium channel modulators |
| US8563566B2 (en) | 2007-08-01 | 2013-10-22 | Valeant Pharmaceuticals International | Naphthyridine derivatives as potassium channel modulators |
| AR070513A1 (es) * | 2007-08-01 | 2010-04-14 | Lundbeck & Co As H | Uso de abridores de canales de potasio kcnq para reducir los sintomas o tratar desordenes o afecciones en las cuales se encuentra anulado el sis-tema dopaminergico como por ejemplo esquizofrenia y trastorno depresivo mayor |
| WO2009016088A1 (en) * | 2007-08-02 | 2009-02-05 | F. Hoffmann-La Roche Ag | The use of benzamide derivatives for the treatment of cns disorders |
| US7786146B2 (en) * | 2007-08-13 | 2010-08-31 | Valeant Pharmaceuticals International | Derivatives of 5-amino-4,6-disubstituted indole and 5-amino-4,6-disubstituted indoline as potassium channel modulators |
| CA2751534A1 (en) * | 2009-03-03 | 2010-09-10 | Pfizer Inc. | Novel phenyl imidazoles and phenyl triazoles as gamma-secretase modulators |
| TWI504395B (zh) | 2009-03-10 | 2015-10-21 | Substituted 3-amino-2-mercaptoquinoline as a KCNQ2 / 3 modifier | |
| TW201038565A (en) | 2009-03-12 | 2010-11-01 | Gruenenthal Gmbh | Substituted 2-mercapto-3-aminopyridines as KCNQ2/3 modulators |
| TWI475020B (zh) | 2009-03-12 | 2015-03-01 | The substituted nicotine amide as a KCNQ2 / 3 modifier | |
| TWI461197B (zh) | 2009-03-12 | 2014-11-21 | 2-mercaptoquinoline-3-carboxamide as a KCNQ2 / 3 modifier | |
| PL2609083T3 (pl) | 2010-08-27 | 2015-07-31 | Gruenenthal Gmbh | Podstawione 2-oksy-chinolino-3-karboksyamidy jako modulatory KCNQ2/3 |
| EP2609084A1 (de) | 2010-08-27 | 2013-07-03 | Grünenthal GmbH | Substituierte 2-aminochinolin-3-carboxamide als kcnq-2/3-modulatoren |
| TWI552750B (zh) | 2010-08-27 | 2016-10-11 | 歌林達股份有限公司 | 作為ｋｃｎｑ２／３鉀離子通道調節劑之經取代之２－氧基－及2－硫基－二氫喹啉－３－羧醯胺 |
| WO2012028300A1 (en) | 2010-09-01 | 2012-03-08 | Grünenthal GmbH | Substituted 1-oxo-dihydroisoquinoline-3-carboxamides as kcnq2/3 modulators |
| WO2015143654A1 (en) * | 2014-03-26 | 2015-10-01 | Merck Sharp & Dohme Corp. | TrkA KINASE INHIBITORS,COMPOSITIONS AND METHODS THEREOF |
| SG11202001310SA (en) | 2017-08-17 | 2020-03-30 | Ikena Oncology Inc | Ahr inhibitors and uses thereof |
| CN113905787A (zh) * | 2019-04-05 | 2022-01-07 | 斯托姆治疗有限公司 | Mettl3抑制化合物 |
Family Cites Families (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2891958A (en) * | 1958-05-29 | 1959-06-23 | Reilly Tar & Chem Corp | Certain alkyl n-pyridylthiopicolinamides and alkyl n-pyridylthiosonicotinamides and process |
| US3835145A (en) | 1972-09-11 | 1974-09-10 | Sterling Drug Inc | 2- and 3-pyridylisothiocyanates |
| JPS57131719A (en) | 1981-02-10 | 1982-08-14 | Chugai Pharmaceut Co Ltd | Blood sugar level lowering agent |
| JPS57206661A (en) * | 1981-06-15 | 1982-12-18 | Chugai Pharmaceut Co Ltd | Acetaminobenzamide derivative |
| JPS5869812A (ja) | 1981-10-22 | 1983-04-26 | Chugai Pharmaceut Co Ltd | 血糖降下剤 |
| DE3305569A1 (de) | 1983-02-18 | 1984-08-23 | Bayer Ag, 5090 Leverkusen | Biscarboxamide zur bekaempfung von erkrankungen sowie verfahren zu ihrer herstellung |
| JPS59175467A (ja) | 1983-03-25 | 1984-10-04 | Chugai Pharmaceut Co Ltd | ウレイドベンズアミド誘導体 |
| JPS59181257A (ja) | 1983-03-31 | 1984-10-15 | Chugai Pharmaceut Co Ltd | ウレイドベンズアミド誘導体 |
| DE3804346A1 (de) * | 1988-02-12 | 1989-08-24 | Boehringer Mannheim Gmbh | Tert.-butylphenyl-pyridyl-amide - verfahren zu ihrer herstellung sowie diese verbindungen enthaltende arzneimittel |
| US5273977A (en) * | 1990-11-05 | 1993-12-28 | Warner-Lambert Company | Substituted tetrahydropyridines and hydroxypiperidines as central nervous system agents |
| JPH08176113A (ja) * | 1993-11-12 | 1996-07-09 | Dainippon Pharmaceut Co Ltd | ２−スルフィニルニコチンアミド誘導体及びその中間体並びにそれを有効成分とする消化性潰瘍治療薬 |
| WO1998037068A1 (en) | 1997-02-21 | 1998-08-27 | Bristol-Myers Squibb Company | Benzoic acid derivatives and related compounds as antiarrhythmic agents |
| JPH10259176A (ja) * | 1997-03-17 | 1998-09-29 | Japan Tobacco Inc | 血管新生阻害作用を有する新規アミド誘導体及びその用途 |
| AU6422098A (en) | 1997-03-24 | 1998-10-20 | Kyowa Hakko Kogyo Co. Ltd. | Benzene derivatives |
| ID23053A (id) | 1997-06-04 | 2000-01-20 | Lilly Co Eli | Karboksamida yang digunakan sebagai agonis 5-ht <if> |
| EP1000035B1 (de) | 1997-07-25 | 2002-11-27 | ALTANA Pharma AG | Substituierte 6-phenylphenanthridine |
| ATE380176T1 (de) | 1999-08-04 | 2007-12-15 | Icagen Inc | Benzanilide als öffner des kaliumkanals |
| CN1391562A (zh) | 1999-09-21 | 2003-01-15 | 阿斯特拉曾尼卡有限公司 | 用作药物的喹唑啉衍生物 |
| CA2397493A1 (en) | 2000-01-27 | 2001-08-02 | Cytovia, Inc. | Substituted nicotinamides and analogs as activators of caspases and inducers of apoptosis and the use thereof |
| HN2002000156A (es) | 2001-07-06 | 2003-11-27 | Inc Agouron Pharmaceuticals | Derivados de benzamida tiazol y composiciones farmaceuticas para inhibir la proliferacion de celulas y metodos para su utilización. |
| UA76512C2 (en) | 2001-09-04 | 2006-08-15 | Boehringer Ingelheim Pharma | Dihydropteridinones, a method for producing thereof and use thereof as medicament |
-
2000
- 2000-08-04 AT AT00955367T patent/ATE380176T1/de not_active IP Right Cessation
- 2000-08-04 WO PCT/US2000/021308 patent/WO2001010380A2/en active IP Right Grant
- 2000-08-04 DE DE60037321A patent/DE60037321D1/de not_active Expired - Lifetime
- 2000-08-04 US US09/632,576 patent/US6372767B1/en not_active Expired - Fee Related
- 2000-08-04 NZ NZ516610A patent/NZ516610A/en not_active IP Right Cessation
- 2000-08-04 CA CA002378241A patent/CA2378241A1/en not_active Abandoned
- 2000-08-04 JP JP2001514905A patent/JP2003506387A/ja active Pending
- 2000-08-04 EP EP00955367A patent/EP1208085B1/de not_active Expired - Lifetime
- 2000-08-04 AU AU67585/00A patent/AU779034B2/en not_active Ceased
- 2000-08-04 DE DE60037321T patent/DE60037321T4/de not_active Expired - Lifetime
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2001
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- 2001-12-06 US US10/004,122 patent/US6737422B2/en not_active Expired - Fee Related
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2002
- 2002-01-21 ZA ZA200200502A patent/ZA200200502B/en unknown
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2004
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Also Published As
| Publication number | Publication date |
|---|---|
| ATE380176T1 (de) | 2007-12-15 |
| JP2003506387A (ja) | 2003-02-18 |
| EP1208085B1 (de) | 2007-12-05 |
| EP1208085A2 (de) | 2002-05-29 |
| WO2001010380A3 (en) | 2001-08-16 |
| EP1208085A4 (de) | 2003-05-02 |
| US20020052393A1 (en) | 2002-05-02 |
| US6372767B1 (en) | 2002-04-16 |
| US20020091122A1 (en) | 2002-07-11 |
| DE60037321T4 (de) | 2010-01-07 |
| US20040157829A1 (en) | 2004-08-12 |
| US6605725B2 (en) | 2003-08-12 |
| US6737422B2 (en) | 2004-05-18 |
| NZ516610A (en) | 2004-05-28 |
| US6989398B2 (en) | 2006-01-24 |
| DE60037321T2 (de) | 2008-11-27 |
| DE60037321D1 (de) | 2008-01-17 |
| WO2001010380A2 (en) | 2001-02-15 |
| AU6758500A (en) | 2001-03-05 |
| CA2378241A1 (en) | 2001-02-15 |
| AU779034B2 (en) | 2005-01-06 |
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