ZA200301633B - Acetamide derivatives and the use thereof as inhibitors of coagulation factor Xa and Vlla. - Google Patents
Acetamide derivatives and the use thereof as inhibitors of coagulation factor Xa and Vlla. Download PDFInfo
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- ZA200301633B ZA200301633B ZA200301633A ZA200301633A ZA200301633B ZA 200301633 B ZA200301633 B ZA 200301633B ZA 200301633 A ZA200301633 A ZA 200301633A ZA 200301633 A ZA200301633 A ZA 200301633A ZA 200301633 B ZA200301633 B ZA 200301633B
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- ZA
- South Africa
- Prior art keywords
- monosubstituted
- coar
- cooa
- coo
- nha
- Prior art date
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- 108010074860 Factor Xa Proteins 0.000 title claims description 14
- 239000003112 inhibitor Substances 0.000 title claims description 5
- 150000003869 acetamides Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 52
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 35
- 125000004432 carbon atom Chemical group C* 0.000 claims description 28
- 150000003839 salts Chemical class 0.000 claims description 23
- 229910052760 oxygen Inorganic materials 0.000 claims description 17
- 238000000034 method Methods 0.000 claims description 16
- 239000012453 solvate Substances 0.000 claims description 16
- 229910052731 fluorine Inorganic materials 0.000 claims description 12
- 238000011282 treatment Methods 0.000 claims description 12
- 206010028980 Neoplasm Diseases 0.000 claims description 11
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 11
- 208000007536 Thrombosis Diseases 0.000 claims description 10
- 239000011737 fluorine Substances 0.000 claims description 10
- 208000034564 Coronary ostial stenosis or atresia Diseases 0.000 claims description 9
- 241001442234 Cosa Species 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 9
- 125000001153 fluoro group Chemical group F* 0.000 claims description 8
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 7
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 6
- 125000002950 monocyclic group Chemical group 0.000 claims description 6
- 230000008569 process Effects 0.000 claims description 6
- 229920006395 saturated elastomer Polymers 0.000 claims description 6
- 238000002399 angioplasty Methods 0.000 claims description 5
- 208000010125 myocardial infarction Diseases 0.000 claims description 5
- 229940037201 oris Drugs 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- 206010002383 Angina Pectoris Diseases 0.000 claims description 4
- 108010039209 Blood Coagulation Factors Proteins 0.000 claims description 4
- 102000015081 Blood Coagulation Factors Human genes 0.000 claims description 4
- 206010061218 Inflammation Diseases 0.000 claims description 4
- 206010022562 Intermittent claudication Diseases 0.000 claims description 4
- 206010027476 Metastases Diseases 0.000 claims description 4
- 239000003114 blood coagulation factor Substances 0.000 claims description 4
- 230000004054 inflammatory process Effects 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 208000037803 restenosis Diseases 0.000 claims description 4
- 125000004434 sulfur atom Chemical group 0.000 claims description 4
- 206010003210 Arteriosclerosis Diseases 0.000 claims description 3
- 208000011775 arteriosclerosis disease Diseases 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- 125000006414 CCl Chemical group ClC* 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims description 2
- 125000002619 bicyclic group Chemical group 0.000 claims description 2
- 239000002671 adjuvant Substances 0.000 claims 1
- VNWKTOKETHGBQD-YPZZEJLDSA-N carbane Chemical group [10CH4] VNWKTOKETHGBQD-YPZZEJLDSA-N 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- -1 aromatic heterocyclic radical Chemical class 0.000 description 78
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- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
- 238000006243 chemical reaction Methods 0.000 description 21
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- 235000019441 ethanol Nutrition 0.000 description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- 239000002904 solvent Substances 0.000 description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
- 230000005764 inhibitory process Effects 0.000 description 10
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 108090000190 Thrombin Proteins 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 8
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 8
- 229960004072 thrombin Drugs 0.000 description 8
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 7
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- 239000012442 inert solvent Substances 0.000 description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
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- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000003146 anticoagulant agent Substances 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 150000002825 nitriles Chemical class 0.000 description 6
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 6
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 6
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- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 5
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- 125000000217 alkyl group Chemical group 0.000 description 5
- 230000002785 anti-thrombosis Effects 0.000 description 5
- 229940127219 anticoagulant drug Drugs 0.000 description 5
- 229910052801 chlorine Inorganic materials 0.000 description 5
- 239000000460 chlorine Substances 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 5
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
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- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 4
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- NBKZGRPRTQELKX-UHFFFAOYSA-N (2-methylpropan-2-yl)oxymethanone Chemical compound CC(C)(C)O[C]=O NBKZGRPRTQELKX-UHFFFAOYSA-N 0.000 description 3
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- 150000001409 amidines Chemical class 0.000 description 3
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- 238000005345 coagulation Methods 0.000 description 3
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- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 3
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C333/00—Derivatives of thiocarbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C333/02—Monothiocarbamic acids; Derivatives thereof
- C07C333/08—Monothiocarbamic acids; Derivatives thereof having nitrogen atoms of thiocarbamic groups bound to carbon atoms of six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/06—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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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- 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
- A61P35/04—Antineoplastic agents specific for metastasis
-
- 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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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C257/00—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines
- C07C257/10—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines
- C07C257/18—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines having carbon atoms of amidino groups bound to carbon atoms of six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
- C07C311/16—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/44—Sulfones; Sulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pain & Pain Management (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Oncology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Hydrogenated Pyridines (AREA)
- Pyridine Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10037146A DE10037146A1 (de) | 2000-07-29 | 2000-07-29 | Acetamidderivate |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200301633B true ZA200301633B (en) | 2004-06-22 |
Family
ID=7650757
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200301633A ZA200301633B (en) | 2000-07-29 | 2003-02-27 | Acetamide derivatives and the use thereof as inhibitors of coagulation factor Xa and Vlla. |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US20030187037A1 (ko) |
| EP (1) | EP1309549A1 (ko) |
| JP (1) | JP2004505106A (ko) |
| KR (1) | KR20030029531A (ko) |
| CN (1) | CN1444561A (ko) |
| AR (1) | AR029999A1 (ko) |
| AU (1) | AU2001281941A1 (ko) |
| BR (1) | BR0112813A (ko) |
| CA (1) | CA2417427A1 (ko) |
| CZ (1) | CZ2003465A3 (ko) |
| DE (1) | DE10037146A1 (ko) |
| HU (1) | HUP0301502A2 (ko) |
| MX (1) | MXPA03000780A (ko) |
| NO (1) | NO20030431D0 (ko) |
| PL (1) | PL358756A1 (ko) |
| SK (1) | SK1972003A3 (ko) |
| WO (1) | WO2002010127A1 (ko) |
| ZA (1) | ZA200301633B (ko) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW200410921A (en) * | 2002-11-25 | 2004-07-01 | Hoffmann La Roche | Mandelic acid derivatives |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19819548A1 (de) * | 1998-04-30 | 1999-11-04 | Merck Patent Gmbh | Biphenylderivate |
| WO2000071511A2 (en) * | 1999-05-24 | 2000-11-30 | Cor Therapeutics, Inc. | INHIBITORS OF FACTOR Xa |
| AU5158100A (en) * | 1999-05-24 | 2000-12-12 | Cor Therapeutics, Inc. | Inhibitors of factor xa |
| WO2001068605A1 (en) * | 2000-03-13 | 2001-09-20 | Pharmacia Corporation | Polycyclic aryl and heteroaryl substituted benzenes useful for selective inhibition of the coagulation cascade |
-
2000
- 2000-07-29 DE DE10037146A patent/DE10037146A1/de not_active Withdrawn
-
2001
- 2001-07-03 EP EP01960449A patent/EP1309549A1/de not_active Withdrawn
- 2001-07-03 PL PL01358756A patent/PL358756A1/xx unknown
- 2001-07-03 MX MXPA03000780A patent/MXPA03000780A/es unknown
- 2001-07-03 BR BR0112813-2A patent/BR0112813A/pt not_active Application Discontinuation
- 2001-07-03 KR KR1020027017990A patent/KR20030029531A/ko not_active Application Discontinuation
- 2001-07-03 CA CA002417427A patent/CA2417427A1/en not_active Abandoned
- 2001-07-03 CN CN01813469A patent/CN1444561A/zh active Pending
- 2001-07-03 SK SK197-2003A patent/SK1972003A3/sk unknown
- 2001-07-03 JP JP2002516259A patent/JP2004505106A/ja active Pending
- 2001-07-03 US US10/343,196 patent/US20030187037A1/en not_active Abandoned
- 2001-07-03 HU HU0301502A patent/HUP0301502A2/hu unknown
- 2001-07-03 CZ CZ2003465A patent/CZ2003465A3/cs unknown
- 2001-07-03 WO PCT/EP2001/007594 patent/WO2002010127A1/de not_active Application Discontinuation
- 2001-07-03 AU AU2001281941A patent/AU2001281941A1/en not_active Abandoned
- 2001-07-27 AR ARP010103584A patent/AR029999A1/es unknown
-
2003
- 2003-01-28 NO NO20030431A patent/NO20030431D0/no not_active Application Discontinuation
- 2003-02-27 ZA ZA200301633A patent/ZA200301633B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CN1444561A (zh) | 2003-09-24 |
| US20030187037A1 (en) | 2003-10-02 |
| AR029999A1 (es) | 2003-07-23 |
| JP2004505106A (ja) | 2004-02-19 |
| CA2417427A1 (en) | 2003-01-27 |
| NO20030431L (no) | 2003-01-28 |
| BR0112813A (pt) | 2003-07-01 |
| MXPA03000780A (es) | 2003-06-04 |
| WO2002010127A1 (de) | 2002-02-07 |
| DE10037146A1 (de) | 2002-02-07 |
| HUP0301502A2 (hu) | 2003-08-28 |
| KR20030029531A (ko) | 2003-04-14 |
| EP1309549A1 (de) | 2003-05-14 |
| AU2001281941A1 (en) | 2002-02-13 |
| NO20030431D0 (no) | 2003-01-28 |
| CZ2003465A3 (cs) | 2003-05-14 |
| PL358756A1 (en) | 2004-08-23 |
| SK1972003A3 (en) | 2003-06-03 |
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