CA2242913A1 - Hydroxamic acid based collagenase inhibitors - Google Patents
Hydroxamic acid based collagenase inhibitors Download PDFInfo
- Publication number
- CA2242913A1 CA2242913A1 CA002242913A CA2242913A CA2242913A1 CA 2242913 A1 CA2242913 A1 CA 2242913A1 CA 002242913 A CA002242913 A CA 002242913A CA 2242913 A CA2242913 A CA 2242913A CA 2242913 A1 CA2242913 A1 CA 2242913A1
- Authority
- CA
- Canada
- Prior art keywords
- compound
- formula
- benzyl
- compounds
- alkyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 239000002253 acid Substances 0.000 title description 17
- NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 title 1
- 239000002442 collagenase inhibitor Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 93
- 125000003118 aryl group Chemical group 0.000 claims abstract description 16
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 15
- 238000012261 overproduction Methods 0.000 claims abstract description 8
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 7
- 239000001257 hydrogen Substances 0.000 claims abstract description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 7
- 238000011321 prophylaxis Methods 0.000 claims abstract description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 5
- 238000011282 treatment Methods 0.000 claims abstract description 5
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 4
- 125000005002 aryl methyl group Chemical group 0.000 claims abstract description 3
- 125000000392 cycloalkenyl group Chemical group 0.000 claims abstract description 3
- 238000000034 method Methods 0.000 claims description 19
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- 150000003839 salts Chemical class 0.000 claims description 8
- 125000005110 aryl thio group Chemical group 0.000 claims description 6
- 125000004468 heterocyclylthio group Chemical group 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 125000006239 protecting group Chemical group 0.000 claims description 6
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
- 125000004414 alkyl thio group Chemical group 0.000 claims description 4
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 3
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- 125000004659 aryl alkyl thio group Chemical group 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
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- 230000008569 process Effects 0.000 claims description 2
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- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 11
- 238000001914 filtration Methods 0.000 description 11
- 239000003112 inhibitor Substances 0.000 description 11
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- 239000012267 brine Substances 0.000 description 10
- -1 cyclo~lk~nyl Chemical group 0.000 description 10
- 125000000623 heterocyclic group Chemical group 0.000 description 10
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
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- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
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- 101100294106 Caenorhabditis elegans nhr-3 gene Proteins 0.000 description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
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- 101150041968 CDC13 gene Proteins 0.000 description 5
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- 102000029816 Collagenase Human genes 0.000 description 5
- 229910052786 argon Inorganic materials 0.000 description 5
- 210000000170 cell membrane Anatomy 0.000 description 5
- 229960002424 collagenase Drugs 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 235000019341 magnesium sulphate Nutrition 0.000 description 5
- 210000001616 monocyte Anatomy 0.000 description 5
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- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
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- 206010020751 Hypersensitivity Diseases 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- 239000002202 Polyethylene glycol Substances 0.000 description 4
- 239000000443 aerosol Substances 0.000 description 4
- 125000003545 alkoxy group Chemical group 0.000 description 4
- 208000026935 allergic disease Diseases 0.000 description 4
- 230000007815 allergy Effects 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 239000000377 silicon dioxide Substances 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 102000008186 Collagen Human genes 0.000 description 3
- 108010035532 Collagen Proteins 0.000 description 3
- 108090000695 Cytokines Proteins 0.000 description 3
- 102000004127 Cytokines Human genes 0.000 description 3
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000001363 autoimmune Effects 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 229920001436 collagen Polymers 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 235000019441 ethanol Nutrition 0.000 description 3
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 3
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- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 2
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
- 241000220479 Acacia Species 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
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- 229920002307 Dextran Polymers 0.000 description 2
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- 108010010803 Gelatin Proteins 0.000 description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur 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
- C07D333/30—Hetero atoms other than halogen
- C07D333/34—Sulfur atoms
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- 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
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- 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]
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
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- 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
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Immunology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9601041.8 | 1996-01-17 | ||
| GBGB9601041.8A GB9601041D0 (en) | 1996-01-17 | 1996-01-17 | Novel compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2242913A1 true CA2242913A1 (en) | 1997-07-24 |
Family
ID=10787226
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002242913A Abandoned CA2242913A1 (en) | 1996-01-17 | 1997-01-14 | Hydroxamic acid based collagenase inhibitors |
Country Status (19)
| Country | Link |
|---|---|
| EP (1) | EP0912545A1 (cs) |
| JP (1) | JP2000503312A (cs) |
| KR (1) | KR19990077325A (cs) |
| CN (1) | CN1213368A (cs) |
| AR (1) | AR005472A1 (cs) |
| AU (1) | AU725056B2 (cs) |
| BR (1) | BR9707024A (cs) |
| CA (1) | CA2242913A1 (cs) |
| CZ (1) | CZ222498A3 (cs) |
| GB (1) | GB9601041D0 (cs) |
| HU (1) | HUP9901022A3 (cs) |
| IL (1) | IL125381A0 (cs) |
| NO (1) | NO983283L (cs) |
| NZ (1) | NZ326352A (cs) |
| PL (1) | PL327820A1 (cs) |
| TR (1) | TR199801380T2 (cs) |
| TW (1) | TW462967B (cs) |
| WO (1) | WO1997026257A1 (cs) |
| ZA (1) | ZA97345B (cs) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6548084B2 (en) | 1995-07-20 | 2003-04-15 | Smithkline Beecham Plc | Controlled release compositions |
| GB9609795D0 (en) * | 1996-05-10 | 1996-07-17 | Smithkline Beecham Plc | Novel compounds |
| WO2000040713A1 (en) * | 1999-01-06 | 2000-07-13 | Mcmaster University | Method of preventing immune and hypersensitivity reactions |
| GB9922825D0 (en) * | 1999-09-25 | 1999-11-24 | Smithkline Beecham Biolog | Medical use |
| WO2002006227A1 (en) * | 2000-07-18 | 2002-01-24 | Chugai Seiyaku Kabushiki Kaisha | Matrix metalloprotease inhibitors |
| CA2473754C (en) * | 2002-01-28 | 2012-04-10 | Aimsco Limited | Treatment of ms with goat serum |
| EP1787986A4 (en) | 2004-08-10 | 2007-08-22 | Shizuoka Coffein Co Ltd | HYDROXAMINE ACID DERIVATIVE AND MEDICAMENT THEREFORE AS AN ACTIVE COMPONENT |
| KR100844277B1 (ko) * | 2005-04-29 | 2008-07-07 | (주)아모레퍼시픽 | 히드록삼산 유도체 및 이의 제조방법 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4743587A (en) * | 1985-09-10 | 1988-05-10 | G. D. Searle & Co. | Hydroxamic acid based collagenase inhibitors |
| GB8827305D0 (en) * | 1988-11-23 | 1988-12-29 | British Bio Technology | Compounds |
| GB9504084D0 (en) * | 1995-03-01 | 1995-04-19 | British Biotech Pharm | Synthesis of carboxylic and hydroxamic acid derivatives |
-
1996
- 1996-01-17 GB GBGB9601041.8A patent/GB9601041D0/en active Pending
-
1997
- 1997-01-14 CZ CZ982224A patent/CZ222498A3/cs unknown
- 1997-01-14 NZ NZ326352A patent/NZ326352A/xx unknown
- 1997-01-14 CN CN97192982A patent/CN1213368A/zh active Pending
- 1997-01-14 HU HU9901022A patent/HUP9901022A3/hu unknown
- 1997-01-14 BR BR9707024A patent/BR9707024A/pt unknown
- 1997-01-14 TR TR1998/01380T patent/TR199801380T2/xx unknown
- 1997-01-14 EP EP97901055A patent/EP0912545A1/en not_active Withdrawn
- 1997-01-14 IL IL12538197A patent/IL125381A0/xx unknown
- 1997-01-14 KR KR1019980705472A patent/KR19990077325A/ko not_active Withdrawn
- 1997-01-14 WO PCT/EP1997/000196 patent/WO1997026257A1/en not_active Ceased
- 1997-01-14 AU AU14436/97A patent/AU725056B2/en not_active Ceased
- 1997-01-14 JP JP9525693A patent/JP2000503312A/ja active Pending
- 1997-01-14 CA CA002242913A patent/CA2242913A1/en not_active Abandoned
- 1997-01-14 PL PL97327820A patent/PL327820A1/xx unknown
- 1997-01-15 AR ARP970100153A patent/AR005472A1/es unknown
- 1997-01-16 ZA ZA97345A patent/ZA97345B/xx unknown
- 1997-01-30 TW TW086101017A patent/TW462967B/zh active
-
1998
- 1998-07-16 NO NO983283A patent/NO983283L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| AU725056B2 (en) | 2000-10-05 |
| IL125381A0 (en) | 1999-03-12 |
| BR9707024A (pt) | 1999-07-20 |
| CZ222498A3 (cs) | 1999-03-17 |
| AU1443697A (en) | 1997-08-11 |
| CN1213368A (zh) | 1999-04-07 |
| PL327820A1 (en) | 1999-01-04 |
| NO983283D0 (no) | 1998-07-16 |
| AR005472A1 (es) | 1999-06-23 |
| WO1997026257A1 (en) | 1997-07-24 |
| JP2000503312A (ja) | 2000-03-21 |
| HUP9901022A3 (en) | 2001-11-28 |
| HUP9901022A2 (hu) | 1999-07-28 |
| ZA97345B (en) | 1998-07-16 |
| EP0912545A1 (en) | 1999-05-06 |
| KR19990077325A (ko) | 1999-10-25 |
| NO983283L (no) | 1998-09-16 |
| TR199801380T2 (xx) | 1998-10-21 |
| GB9601041D0 (en) | 1996-03-20 |
| TW462967B (en) | 2001-11-11 |
| NZ326352A (en) | 2000-03-27 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |