HRP20030451A2 - Tetralone derivatives as antitumor agents - Google Patents
Tetralone derivatives as antitumor agents Download PDFInfo
- Publication number
- HRP20030451A2 HRP20030451A2 HR20030451A HRP20030451A HRP20030451A2 HR P20030451 A2 HRP20030451 A2 HR P20030451A2 HR 20030451 A HR20030451 A HR 20030451A HR P20030451 A HRP20030451 A HR P20030451A HR P20030451 A2 HRP20030451 A2 HR P20030451A2
- Authority
- HR
- Croatia
- Prior art keywords
- oxo
- tetrahydro
- formula
- naphthalen
- alkyl
- Prior art date
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- 239000002246 antineoplastic agent Substances 0.000 title description 2
- XHLHPRDBBAGVEG-UHFFFAOYSA-N 1-tetralone Chemical class C1=CC=C2C(=O)CCCC2=C1 XHLHPRDBBAGVEG-UHFFFAOYSA-N 0.000 title 1
- -1 trifluoromethyl- Chemical group 0.000 claims description 89
- 150000001875 compounds Chemical class 0.000 claims description 74
- 238000006243 chemical reaction Methods 0.000 claims description 51
- 239000002253 acid Substances 0.000 claims description 48
- 125000000217 alkyl group Chemical group 0.000 claims description 35
- 238000000034 method Methods 0.000 claims description 28
- 229910052739 hydrogen Inorganic materials 0.000 claims description 17
- 239000001257 hydrogen Substances 0.000 claims description 17
- 150000003839 salts Chemical class 0.000 claims description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
- 102000003964 Histone deacetylase Human genes 0.000 claims description 9
- 108090000353 Histone deacetylase Proteins 0.000 claims description 9
- 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 description 8
- 150000007513 acids Chemical class 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 8
- 125000006239 protecting group Chemical group 0.000 claims description 8
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 6
- 125000003282 alkyl amino group Chemical group 0.000 claims description 6
- 125000002947 alkylene group Chemical group 0.000 claims description 6
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 6
- 125000005843 halogen group Chemical group 0.000 claims description 6
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 230000006907 apoptotic process Effects 0.000 claims description 5
- 125000004104 aryloxy group Chemical group 0.000 claims description 5
- 239000003112 inhibitor Substances 0.000 claims description 5
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 5
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 125000001072 heteroaryl group Chemical group 0.000 claims description 4
- 229920006395 saturated elastomer Polymers 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 229940079593 drug Drugs 0.000 claims description 3
- 150000002431 hydrogen Chemical group 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- YAJQOFDUXGXPGB-UHFFFAOYSA-N 6-(7-chloro-2-methyl-1-oxo-3,4-dihydronaphthalen-2-yl)-n-hydroxyhexanamide Chemical compound C1=C(Cl)C=C2C(=O)C(C)(CCCCCC(=O)NO)CCC2=C1 YAJQOFDUXGXPGB-UHFFFAOYSA-N 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims description 2
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- 239000000243 solution Substances 0.000 description 32
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- 239000000203 mixture Substances 0.000 description 17
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- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 9
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- 201000011510 cancer Diseases 0.000 description 8
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- 238000003756 stirring Methods 0.000 description 7
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 6
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- 210000004027 cell Anatomy 0.000 description 5
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- 125000004494 ethyl ester group Chemical group 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 238000005469 granulation Methods 0.000 description 5
- 230000003179 granulation Effects 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 238000000926 separation method Methods 0.000 description 5
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 4
- KLDLRDSRCMJKGM-UHFFFAOYSA-N 3-[chloro-(2-oxo-1,3-oxazolidin-3-yl)phosphoryl]-1,3-oxazolidin-2-one Chemical compound C1COC(=O)N1P(=O)(Cl)N1CCOC1=O KLDLRDSRCMJKGM-UHFFFAOYSA-N 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 4
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- 150000008064 anhydrides Chemical class 0.000 description 4
- 230000000259 anti-tumor effect Effects 0.000 description 4
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Classifications
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- C—CHEMISTRY; METALLURGY
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/57—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of rings other than six-membered aromatic rings
- C07C233/60—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of rings other than six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/10—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms
- C07D295/112—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms with the ring nitrogen atoms and the doubly bound oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
- C07D295/116—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms with the ring nitrogen atoms and the doubly bound oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings with the doubly bound oxygen or sulfur atoms directly attached to a carbocyclic ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- 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
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C259/00—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups
- C07C259/04—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids
- C07C259/06—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids having carbon atoms of hydroxamic groups bound to hydrogen atoms or to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- C07D213/24—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 substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/44—Radicals substituted by doubly-bound oxygen, sulfur, or nitrogen atoms, or by two such atoms singly-bound to the same carbon atom
- C07D213/46—Oxygen atoms
- C07D213/50—Ketonic radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/10—One of the condensed rings being a six-membered aromatic ring the other ring being six-membered, e.g. tetraline
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
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- Oncology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP00126820 | 2000-12-07 | ||
| PCT/EP2001/014311 WO2002046144A1 (en) | 2000-12-07 | 2001-12-06 | Tetralone derivatives as antitumor agents |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20030451A2 true HRP20030451A2 (en) | 2005-04-30 |
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| Application Number | Title | Priority Date | Filing Date |
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| HR20030451A HRP20030451A2 (en) | 2000-12-07 | 2003-06-04 | Tetralone derivatives as antitumor agents |
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| EP (1) | EP1349830A1 (de) |
| JP (1) | JP4091431B2 (de) |
| KR (1) | KR20030077551A (de) |
| CN (1) | CN100340545C (de) |
| AR (1) | AR035659A1 (de) |
| AU (2) | AU2002216074C1 (de) |
| BG (1) | BG107889A (de) |
| BR (1) | BR0115988A (de) |
| CA (1) | CA2430355A1 (de) |
| CZ (1) | CZ20031833A3 (de) |
| EC (1) | ECSP034642A (de) |
| HK (1) | HK1060875A1 (de) |
| HR (1) | HRP20030451A2 (de) |
| HU (1) | HUP0400579A2 (de) |
| IL (1) | IL156133A0 (de) |
| MA (1) | MA26972A1 (de) |
| MX (1) | MXPA03004947A (de) |
| NO (1) | NO20032531L (de) |
| NZ (1) | NZ526051A (de) |
| PL (1) | PL365324A1 (de) |
| RU (1) | RU2288220C2 (de) |
| SK (1) | SK8512003A3 (de) |
| WO (1) | WO2002046144A1 (de) |
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| US6822267B1 (en) * | 1997-08-20 | 2004-11-23 | Advantest Corporation | Signal transmission circuit, CMOS semiconductor device, and circuit board |
| US6706686B2 (en) * | 2001-09-27 | 2004-03-16 | The Regents Of The University Of Colorado | Inhibition of histone deacetylase as a treatment for cardiac hypertrophy |
| EP2269609A3 (de) * | 2001-10-16 | 2012-07-11 | Sloan-Kettering Institute for Cancer Research | Behandlung von neurodegenerativen Erkrankungen und Gehirnkrebs mit Suberoylanilid-Hydroxyamsäure (SAHA) |
| US7456219B2 (en) | 2002-03-04 | 2008-11-25 | Merck Hdac Research, Llc | Polymorphs of suberoylanilide hydroxamic acid |
| CA2632078C (en) | 2002-03-04 | 2012-08-14 | Sloan-Kettering Institute For Cancer Research | Methods of inducing terminal differentiation |
| US7148257B2 (en) | 2002-03-04 | 2006-12-12 | Merck Hdac Research, Llc | Methods of treating mesothelioma with suberoylanilide hydroxamic acid |
| US20040077591A1 (en) * | 2002-03-28 | 2004-04-22 | The Brigham And Women's Hospital, Inc. | Histone deacetylase inhibitors for the treatment of multiple sclerosis, amyotrophic lateral sclerosis and Alzheimer's Disease |
| EP1492596A1 (de) * | 2002-04-05 | 2005-01-05 | Fujisawa Pharmaceutical Co., Ltd. | Depsipeptid zur behandlung von nierenkrebs |
| CN100566711C (zh) * | 2002-04-15 | 2009-12-09 | 斯隆-凯特林癌症研究院 | 治疗癌症的化合物及其用途 |
| GB0217777D0 (en) * | 2002-07-31 | 2002-09-11 | Novartis Ag | Organic compounds |
| US7154002B1 (en) | 2002-10-08 | 2006-12-26 | Takeda San Diego, Inc. | Histone deacetylase inhibitors |
| US7250514B1 (en) | 2002-10-21 | 2007-07-31 | Takeda San Diego, Inc. | Histone deacetylase inhibitors |
| JP2006509010A (ja) * | 2002-12-05 | 2006-03-16 | インペリアル・カレッジ・イノベイションズ・リミテッド | アポトーシスの制御 |
| JP2006520796A (ja) * | 2003-03-17 | 2006-09-14 | タケダ サン ディエゴ インコーポレイテッド | ヒストンデアセチラーゼインヒビター |
| CN102188415A (zh) | 2003-08-26 | 2011-09-21 | 默克Hdac研究有限责任公司 | 用hdac抑制剂治疗癌症的方法 |
| CA2535889A1 (en) | 2003-08-29 | 2005-03-17 | Aton Pharma, Inc. | Combination methods of treating cancer |
| WO2005065681A1 (en) * | 2003-12-19 | 2005-07-21 | Takeda San Diego, Inc. | N- hydroxy-3-(3-(1h-imidazol-2-yl)-phenyl)-acrylamide derivatives and related compounds as histone deacetylase (hdac) inhibitors for the treatment of cancer |
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| US4448730A (en) * | 1981-03-24 | 1984-05-15 | Riet Bartholomeus Van T | Hydroxybenzohydroxamic acids, benzamides and esters and related compounds as ribonucleotide reductase inhibitors |
| JPS61176523A (ja) * | 1985-01-30 | 1986-08-08 | Teruhiko Beppu | 制癌剤 |
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2001
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- 2001-12-06 CZ CZ20031833A patent/CZ20031833A3/cs unknown
- 2001-12-06 YU YU45803A patent/YU45803A/sh unknown
- 2001-12-06 PL PL01365324A patent/PL365324A1/xx not_active Application Discontinuation
- 2001-12-06 AU AU2002216074A patent/AU2002216074C1/en not_active Ceased
- 2001-12-06 CA CA002430355A patent/CA2430355A1/en not_active Abandoned
- 2001-12-06 KR KR10-2003-7007640A patent/KR20030077551A/ko not_active Application Discontinuation
- 2001-12-06 EP EP01999552A patent/EP1349830A1/de not_active Withdrawn
- 2001-12-06 RU RU2003119658/04A patent/RU2288220C2/ru active
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| NO20032531D0 (no) | 2003-06-04 |
| NZ526051A (en) | 2004-12-24 |
| EP1349830A1 (de) | 2003-10-08 |
| YU45803A (sh) | 2006-05-25 |
| ECSP034642A (es) | 2003-07-25 |
| NO20032531L (no) | 2003-06-04 |
| AU1607402A (en) | 2002-06-18 |
| CN100340545C (zh) | 2007-10-03 |
| HUP0400579A2 (hu) | 2004-06-28 |
| WO2002046144A1 (en) | 2002-06-13 |
| US20020065282A1 (en) | 2002-05-30 |
| BG107889A (bg) | 2004-06-30 |
| JP4091431B2 (ja) | 2008-05-28 |
| MXPA03004947A (es) | 2003-09-10 |
| CA2430355A1 (en) | 2002-06-13 |
| KR20030077551A (ko) | 2003-10-01 |
| MA26972A1 (fr) | 2004-12-20 |
| HK1060875A1 (en) | 2004-08-27 |
| CZ20031833A3 (cs) | 2004-02-18 |
| ZA200304262B (en) | 2004-08-30 |
| BR0115988A (pt) | 2004-01-13 |
| AU2002216074C1 (en) | 2006-12-07 |
| PL365324A1 (en) | 2004-12-27 |
| AR035659A1 (es) | 2004-06-23 |
| IL156133A0 (en) | 2003-12-23 |
| CN1478072A (zh) | 2004-02-25 |
| SK8512003A3 (en) | 2004-04-06 |
| JP2004515488A (ja) | 2004-05-27 |
| AU2002216074B2 (en) | 2006-01-05 |
| US6531472B2 (en) | 2003-03-11 |
| RU2288220C2 (ru) | 2006-11-27 |
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