AU2002358735B9 - Phenoxy piperidines for treating diseases such as schizophrenia and depression - Google Patents
Phenoxy piperidines for treating diseases such as schizophrenia and depression Download PDFInfo
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- AU2002358735B9 AU2002358735B9 AU2002358735A AU2002358735A AU2002358735B9 AU 2002358735 B9 AU2002358735 B9 AU 2002358735B9 AU 2002358735 A AU2002358735 A AU 2002358735A AU 2002358735 A AU2002358735 A AU 2002358735A AU 2002358735 B9 AU2002358735 B9 AU 2002358735B9
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims description 12
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- AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 description 1
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- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
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- 150000002825 nitriles Chemical class 0.000 description 1
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- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
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- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical class C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
- 150000004866 oxadiazoles Chemical class 0.000 description 1
- 125000003232 p-nitrobenzoyl group Chemical group [N+](=O)([O-])C1=CC=C(C(=O)*)C=C1 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
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- OAHKWDDSKCRNFE-UHFFFAOYSA-N phenylmethanesulfonyl chloride Chemical compound ClS(=O)(=O)CC1=CC=CC=C1 OAHKWDDSKCRNFE-UHFFFAOYSA-N 0.000 description 1
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- DROIHSMGGKKIJT-UHFFFAOYSA-N propane-1-sulfonamide Chemical compound CCCS(N)(=O)=O DROIHSMGGKKIJT-UHFFFAOYSA-N 0.000 description 1
- KPBSJEBFALFJTO-UHFFFAOYSA-N propane-1-sulfonyl chloride Chemical compound CCCS(Cl)(=O)=O KPBSJEBFALFJTO-UHFFFAOYSA-N 0.000 description 1
- DRINJBFRTLBHNF-UHFFFAOYSA-N propane-2-sulfonyl chloride Chemical compound CC(C)S(Cl)(=O)=O DRINJBFRTLBHNF-UHFFFAOYSA-N 0.000 description 1
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- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
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- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
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- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
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- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
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- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical class ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
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- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
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- SMBZJSVIKJMSFP-UHFFFAOYSA-N trifluoromethyl hypofluorite Chemical compound FOC(F)(F)F SMBZJSVIKJMSFP-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no 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
- C07D211/40—Oxygen atoms
- C07D211/44—Oxygen atoms attached in position 4
- C07D211/46—Oxygen atoms attached in position 4 having a hydrogen atom as the second substituent in position 4
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- 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
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- 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
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- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- 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
- A61P25/22—Anxiolytics
-
- 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
- A61P25/24—Antidepressants
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/34—Tobacco-abuse
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Psychiatry (AREA)
- Epidemiology (AREA)
- Psychology (AREA)
- Addiction (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10201550.3 | 2002-01-17 | ||
| DE10201550A DE10201550A1 (de) | 2002-01-17 | 2002-01-17 | Phenoxy-Piperidine |
| PCT/EP2002/014389 WO2003059882A1 (de) | 2002-01-17 | 2002-12-17 | Phenoxy-piperidine zur behandlung von erkrankungen wie schizophenie und depression |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| AU2002358735A1 AU2002358735A1 (en) | 2003-07-30 |
| AU2002358735B2 AU2002358735B2 (en) | 2009-03-12 |
| AU2002358735B9 true AU2002358735B9 (en) | 2009-04-09 |
Family
ID=7712334
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2002358735A Ceased AU2002358735B9 (en) | 2002-01-17 | 2002-12-17 | Phenoxy piperidines for treating diseases such as schizophrenia and depression |
Country Status (11)
| Country | Link |
|---|---|
| US (2) | US20050131021A1 (enExample) |
| EP (1) | EP1465868A1 (enExample) |
| JP (1) | JP4727925B2 (enExample) |
| CN (1) | CN1615297A (enExample) |
| AU (1) | AU2002358735B9 (enExample) |
| CA (1) | CA2473409C (enExample) |
| DE (1) | DE10201550A1 (enExample) |
| HU (1) | HUP0500497A2 (enExample) |
| PL (1) | PL373946A1 (enExample) |
| WO (1) | WO2003059882A1 (enExample) |
| ZA (1) | ZA200406504B (enExample) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AR046783A1 (es) * | 2003-12-03 | 2005-12-21 | Glaxo Group Ltd | Compuesto de sal ciclica de amonio cuaternario composicion farmaceutica que lo comprende y su uso para preparar esta ultima |
| AU2006282896A1 (en) | 2005-08-26 | 2007-03-01 | Braincells, Inc. | Neurogenesis by muscarinic receptor modulation |
| US8787440B2 (en) * | 2008-07-25 | 2014-07-22 | Qualcomm Incorporated | Determination of receive data values |
| US9630929B2 (en) | 2011-10-31 | 2017-04-25 | Xenon Pharmaceuticals Inc. | Benzenesulfonamide compounds and their use as therapeutic agents |
| RU2014121983A (ru) | 2011-10-31 | 2015-12-10 | Ксенон Фармасьютикалз Инк. | Биарильные простоэфирные сульфонамиды и их применение в качестве терапевтических средств |
| US8952169B2 (en) | 2012-05-22 | 2015-02-10 | Xenon Pharmaceuticals Inc. | N-substituted benzamides and methods of use thereof |
| CN104797555B (zh) | 2012-07-06 | 2017-12-22 | 基因泰克公司 | N‑取代的苯甲酰胺及其使用方法 |
| HK1213476A1 (zh) | 2013-03-14 | 2016-07-08 | 基因泰克公司 | 取代的三唑並吡啶及其使用方法 |
| CA2898680A1 (en) | 2013-03-15 | 2014-09-18 | Genentech,Inc. | Substituted benzoxazoles and methods of use thereof |
| CA2931732A1 (en) | 2013-11-27 | 2015-06-04 | Genentech, Inc. | Substituted benzamides and methods of use thereof |
| WO2016007534A1 (en) | 2014-07-07 | 2016-01-14 | Genentech, Inc. | Therapeutic compounds and methods of use thereof |
| PE20180575A1 (es) | 2015-05-22 | 2018-04-04 | Genentech Inc | Benzamidas sustituidas y metodos para utilizarlas |
| MA42683A (fr) | 2015-08-27 | 2018-07-04 | Genentech Inc | Composés thérapeutiques et leurs méthodes utilisation |
| BR112018006189A2 (pt) | 2015-09-28 | 2018-10-09 | Genentech Inc | compostos da fórmula, composição farmacêutica, métodos de tratamento de uma doença, de diminuição do fluxo de íons e de tratamento de prurido em um mamífero, método para tratamento de dores em um mamífero e uso de um composto |
| JP2018535234A (ja) | 2015-11-25 | 2018-11-29 | ジェネンテック， インコーポレイテッド | ナトリウムチャネル遮断薬として有用な置換ベンズアミド |
| CN109071426A (zh) | 2016-03-30 | 2018-12-21 | 基因泰克公司 | 取代的苯甲酰胺及其使用方法 |
| WO2018072602A1 (en) | 2016-10-17 | 2018-04-26 | Genentech, Inc. | Therapeutic compounds and methods of use thereof |
| WO2018112842A1 (en) | 2016-12-22 | 2018-06-28 | Merck Sharp & Dohme Corp. | 6,6-fused heteroaryl piperidine ether allosteric modulators of m4 muscarinic acetylcholine receptor |
| WO2018112840A1 (en) | 2016-12-22 | 2018-06-28 | Merck Sharp & Dohme Corp. | 6, 5-fused heteroaryl piperidine ether allosteric modulators of the m4 muscarinic acetylcholine receptor |
| WO2018112843A1 (en) * | 2016-12-22 | 2018-06-28 | Merck Sharp & Dohme Corp. | Heteroaryl piperidine ether allosteric modulators of the m4 muscarinic acetylcholine receptor |
| JP2020511511A (ja) | 2017-03-24 | 2020-04-16 | ジェネンテック， インコーポレイテッド | ナトリウムチャネル阻害剤としての４−ピペリジン−ｎ−（ピリミジン−４−イル）クロマン−７−スルホンアミド誘導体 |
| EP3759098A1 (en) | 2018-02-26 | 2021-01-06 | Genentech, Inc. | Pyridine-sulfonamide compounds and their use against pain and related conditions |
| US10947251B2 (en) | 2018-03-30 | 2021-03-16 | Genentech, Inc. | Therapeutic compounds and methods of use thereof |
| TW202003490A (zh) | 2018-05-22 | 2020-01-16 | 瑞士商赫孚孟拉羅股份公司 | 治療性化合物及其使用方法 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2776293A (en) * | 1950-08-09 | 1957-01-01 | Nopco Chem Co | Improved hydrogenation process |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4216218A (en) * | 1979-02-23 | 1980-08-05 | American Hoechst Corporation | Antidepressant and analgesic 4-aryloxy- and 4-arylthio-3-phenylpiperidines |
| EG18188A (en) * | 1986-05-01 | 1992-09-30 | Pfizer Ltd | Process for preparation anti-arhythmia agents |
| US5093341A (en) * | 1987-12-17 | 1992-03-03 | Merrell Dow Pharmaceuticals Inc. | N-aralkyl piperidine derivatives useful as antithrombolytic agents |
| US5169855A (en) * | 1990-03-28 | 1992-12-08 | Du Pont Merck Pharmaceutical Company | Piperidine ether derivatives as psychotropic drugs or plant fungicides |
| US5202346A (en) * | 1992-02-25 | 1993-04-13 | American Home Products Corporation | Piperidinyl and piperazinyl derivatives |
| IL117149A0 (en) * | 1995-02-23 | 1996-06-18 | Schering Corp | Muscarinic antagonists |
| ZA9610741B (en) * | 1995-12-22 | 1997-06-24 | Warner Lambert Co | 4-Substituted piperidine analogs and their use as subtype selective nmda receptor antagonists |
| HUP9904363A3 (en) * | 1996-08-15 | 2000-12-28 | Schering Corp | Piperidine ether muscarinic antagonists and pharmaceutical compositions containing them |
| GB9725541D0 (en) * | 1997-12-02 | 1998-02-04 | Pharmacia & Upjohn Spa | Amino-benzothiazole derivatives |
| DE10000739A1 (de) * | 2000-01-11 | 2001-07-12 | Merck Patent Gmbh | Piperidin- und Piperazinderivate |
| JP2002363159A (ja) * | 2001-04-05 | 2002-12-18 | Sankyo Co Ltd | ベンズアミジン誘導体 |
| US20040180401A1 (en) * | 2002-05-24 | 2004-09-16 | Neurion Pharmaceuticals, Inc. | Methods of determining precise HERG interactions and designing compounds based on said interactions |
-
2002
- 2002-01-17 DE DE10201550A patent/DE10201550A1/de not_active Withdrawn
- 2002-12-17 CA CA2473409A patent/CA2473409C/en not_active Expired - Fee Related
- 2002-12-17 WO PCT/EP2002/014389 patent/WO2003059882A1/de not_active Ceased
- 2002-12-17 CN CNA028272544A patent/CN1615297A/zh active Pending
- 2002-12-17 EP EP02793045A patent/EP1465868A1/de not_active Withdrawn
- 2002-12-17 PL PL02373946A patent/PL373946A1/xx unknown
- 2002-12-17 US US10/501,763 patent/US20050131021A1/en not_active Abandoned
- 2002-12-17 AU AU2002358735A patent/AU2002358735B9/en not_active Ceased
- 2002-12-17 JP JP2003559986A patent/JP4727925B2/ja not_active Expired - Fee Related
- 2002-12-17 HU HU0500497A patent/HUP0500497A2/hu unknown
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2004
- 2004-08-16 ZA ZA200406504A patent/ZA200406504B/en unknown
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2009
- 2009-02-26 US US12/393,480 patent/US20090247584A1/en not_active Abandoned
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2776293A (en) * | 1950-08-09 | 1957-01-01 | Nopco Chem Co | Improved hydrogenation process |
Non-Patent Citations (4)
| Title |
|---|
| CA abstract 133:207639 & Tang et al. Zhongguo Yaoke Daxue Xuebao 2000, 31(2), 81 * |
| Hahn et al. Helv. Chem. Acta. 1943, 1132 * |
| Larsen et al. J. Am. Chem. Soc. 1986, 108, 3512 * |
| Lloyd et al. J. Chem. Soc., Perkin Trans. 1 2000, 165 * |
Also Published As
| Publication number | Publication date |
|---|---|
| HUP0500497A2 (hu) | 2005-08-29 |
| WO2003059882A1 (de) | 2003-07-24 |
| CA2473409C (en) | 2011-09-27 |
| US20050131021A1 (en) | 2005-06-16 |
| EP1465868A1 (de) | 2004-10-13 |
| JP4727925B2 (ja) | 2011-07-20 |
| CN1615297A (zh) | 2005-05-11 |
| ZA200406504B (en) | 2005-09-15 |
| AU2002358735B2 (en) | 2009-03-12 |
| JP2005514457A (ja) | 2005-05-19 |
| DE10201550A1 (de) | 2003-07-31 |
| CA2473409A1 (en) | 2003-07-24 |
| US20090247584A1 (en) | 2009-10-01 |
| AU2002358735A1 (en) | 2003-07-30 |
| PL373946A1 (en) | 2005-09-19 |
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