ZA200104981B - Heteroaryl acetylenic sulfonamide and phosphinic acid amide hydroxamic acid tace inhibitors. - Google Patents
Heteroaryl acetylenic sulfonamide and phosphinic acid amide hydroxamic acid tace inhibitors. Download PDFInfo
- Publication number
- ZA200104981B ZA200104981B ZA200104981A ZA200104981A ZA200104981B ZA 200104981 B ZA200104981 B ZA 200104981B ZA 200104981 A ZA200104981 A ZA 200104981A ZA 200104981 A ZA200104981 A ZA 200104981A ZA 200104981 B ZA200104981 B ZA 200104981B
- Authority
- ZA
- South Africa
- Prior art keywords
- carbon atoms
- alkyl
- compound
- hydrogen
- aryl
- Prior art date
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- 125000001072 heteroaryl group Chemical group 0.000 title claims description 22
- 239000002253 acid Substances 0.000 title claims description 19
- 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 claims description 14
- 229940124530 sulfonamide Drugs 0.000 title description 19
- 150000003456 sulfonamides Chemical class 0.000 title description 17
- 239000002447 tumor necrosis factor alpha converting enzyme inhibitor Substances 0.000 title description 8
- ACVYVLVWPXVTIT-UHFFFAOYSA-N phosphinic acid Chemical compound O[PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-N 0.000 title description 6
- 150000001875 compounds Chemical class 0.000 claims description 81
- 125000004432 carbon atom Chemical group C* 0.000 claims description 77
- 229910052739 hydrogen Inorganic materials 0.000 claims description 39
- 239000001257 hydrogen Substances 0.000 claims description 39
- 125000000217 alkyl group Chemical group 0.000 claims description 38
- 229910052760 oxygen Inorganic materials 0.000 claims description 35
- 229910052717 sulfur Inorganic materials 0.000 claims description 30
- 125000003118 aryl group Chemical group 0.000 claims description 29
- 238000000034 method Methods 0.000 claims description 26
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 24
- 125000005842 heteroatom Chemical group 0.000 claims description 24
- 150000002431 hydrogen Chemical class 0.000 claims description 21
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
- 239000000203 mixture Substances 0.000 claims description 17
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 17
- 150000003839 salts Chemical class 0.000 claims description 17
- 125000001424 substituent group Chemical group 0.000 claims description 17
- -1 1,2.4-triazolyl Chemical group 0.000 claims description 16
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 16
- 125000003342 alkenyl group Chemical group 0.000 claims description 12
- 125000000304 alkynyl group Chemical group 0.000 claims description 12
- 125000006239 protecting group Chemical group 0.000 claims description 11
- 102100040247 Tumor necrosis factor Human genes 0.000 claims description 9
- 125000001624 naphthyl group Chemical group 0.000 claims description 9
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 7
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 6
- 102000004190 Enzymes Human genes 0.000 claims description 5
- 108090000790 Enzymes Proteins 0.000 claims description 5
- 125000004429 atom Chemical group 0.000 claims description 5
- 239000000460 chlorine Chemical group 0.000 claims description 5
- 239000011737 fluorine Substances 0.000 claims description 5
- 229910052731 fluorine Inorganic materials 0.000 claims description 5
- 230000001404 mediated effect Effects 0.000 claims description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- 208000031886 HIV Infections Diseases 0.000 claims description 4
- 208000037357 HIV infectious disease Diseases 0.000 claims description 4
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 4
- 206010022489 Insulin Resistance Diseases 0.000 claims description 4
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- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
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- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 3
- 206010040070 Septic Shock Diseases 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
- 229910052794 bromium Inorganic materials 0.000 claims description 3
- 210000003169 central nervous system Anatomy 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 208000027866 inflammatory disease Diseases 0.000 claims description 3
- 230000004054 inflammatory process Effects 0.000 claims description 3
- 230000002401 inhibitory effect Effects 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
- 230000036303 septic shock Effects 0.000 claims description 3
- 229910006069 SO3H Inorganic materials 0.000 claims description 2
- 150000007514 bases Chemical class 0.000 claims description 2
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims 6
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims 3
- 241000124008 Mammalia Species 0.000 claims 3
- 206010037660 Pyrexia Diseases 0.000 claims 2
- 231100000915 pathological change Toxicity 0.000 claims 2
- 230000036285 pathological change Effects 0.000 claims 2
- JDJPRVGKWLAXHE-UHFFFAOYSA-N 3-[(4-but-2-ynoxyphenyl)sulfonylamino]-n-hydroxy-2,6-dimethoxypyridine-4-carboxamide Chemical compound COC1=NC(OC)=CC(C(=O)NO)=C1NS(=O)(=O)C1=CC=C(OCC#CC)C=C1 JDJPRVGKWLAXHE-UHFFFAOYSA-N 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 125000006413 ring segment Chemical group 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 description 20
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
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- 102000002274 Matrix Metalloproteinases Human genes 0.000 description 9
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 8
- 230000029936 alkylation Effects 0.000 description 7
- 238000005804 alkylation reaction Methods 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- 150000003573 thiols Chemical class 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 150000003862 amino acid derivatives Chemical class 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 239000003112 inhibitor Substances 0.000 description 6
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- 108010016113 Matrix Metalloproteinase 1 Proteins 0.000 description 5
- 102000000380 Matrix Metalloproteinase 1 Human genes 0.000 description 5
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
- 150000001412 amines Chemical class 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 239000012312 sodium hydride Substances 0.000 description 5
- 229910000104 sodium hydride Inorganic materials 0.000 description 5
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
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- 238000010511 deprotection reaction Methods 0.000 description 4
- 125000002534 ethynyl group Chemical class [H]C#C* 0.000 description 4
- 229910052736 halogen Inorganic materials 0.000 description 4
- 238000004949 mass spectrometry Methods 0.000 description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 230000003287 optical effect Effects 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 239000012453 solvate Substances 0.000 description 4
- KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 description 3
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- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 229940124761 MMP inhibitor Drugs 0.000 description 3
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- 239000003153 chemical reaction reagent Substances 0.000 description 3
- XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 3
- 229940088598 enzyme Drugs 0.000 description 3
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 3
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- 239000007858 starting material Substances 0.000 description 3
- 150000003460 sulfonic acids Chemical class 0.000 description 3
- 230000006103 sulfonylation Effects 0.000 description 3
- 238000005694 sulfonylation reaction Methods 0.000 description 3
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 3
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- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
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Classifications
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
- C07C309/78—Halides of sulfonic acids
- C07C309/86—Halides of sulfonic acids having halosulfonyl groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C309/87—Halides of sulfonic acids having halosulfonyl groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing singly-bound oxygen atoms bound to the carbon skeleton
-
- 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
- C07D231/14—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 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
- C07D231/38—Nitrogen atoms
- C07D231/42—Benzene-sulfonamido pyrazoles
-
- 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
- C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oncology (AREA)
- Diabetes (AREA)
- Physical Education & Sports Medicine (AREA)
- Immunology (AREA)
- Communicable Diseases (AREA)
- Rheumatology (AREA)
- Urology & Nephrology (AREA)
- Virology (AREA)
- Hematology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Dermatology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Obesity (AREA)
- Endocrinology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Vascular Medicine (AREA)
- Ophthalmology & Optometry (AREA)
- Pain & Pain Management (AREA)
- AIDS & HIV (AREA)
- Gastroenterology & Hepatology (AREA)
- Emergency Medicine (AREA)
- Transplantation (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US23909199A | 1999-01-27 | 1999-01-27 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200104981B true ZA200104981B (en) | 2002-10-08 |
Family
ID=22900572
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200104981A ZA200104981B (en) | 1999-01-27 | 2001-06-18 | Heteroaryl acetylenic sulfonamide and phosphinic acid amide hydroxamic acid tace inhibitors. |
Country Status (22)
| Country | Link |
|---|---|
| EP (1) | EP1147102B1 (es) |
| JP (1) | JP2002535399A (es) |
| KR (1) | KR20010101731A (es) |
| CN (1) | CN1144785C (es) |
| AR (1) | AR022422A1 (es) |
| AT (1) | ATE261955T1 (es) |
| AU (1) | AU769182B2 (es) |
| BR (1) | BR0007726A (es) |
| CA (1) | CA2356481A1 (es) |
| CZ (1) | CZ20012708A3 (es) |
| DE (1) | DE60009035T2 (es) |
| DK (1) | DK1147102T3 (es) |
| EA (1) | EA200100805A1 (es) |
| ES (1) | ES2215621T3 (es) |
| HU (1) | HUP0105434A3 (es) |
| IL (1) | IL144346A0 (es) |
| NO (1) | NO20013681D0 (es) |
| NZ (1) | NZ512368A (es) |
| PL (1) | PL349768A1 (es) |
| PT (1) | PT1147102E (es) |
| WO (1) | WO2000044740A2 (es) |
| ZA (1) | ZA200104981B (es) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7199155B2 (en) | 2002-12-23 | 2007-04-03 | Wyeth Holdings Corporation | Acetylenic aryl sulfonate hydroxamic acid TACE and matrix metalloproteinase inhibitors |
| US20210393632A1 (en) | 2018-10-04 | 2021-12-23 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Egfr inhibitors for treating keratodermas |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE229949T1 (de) * | 1996-10-16 | 2003-01-15 | American Cyanamid Co | Herstellung und verwendung von ortho-sulfonamido- heteroarylhydroxamsäuren als matrix- metalloproteinase und tace inhibitoren |
| AU769180B2 (en) * | 1999-01-27 | 2004-01-15 | Wyeth Holdings Corporation | Acetylenic aryl sulfonamide and phosphinic acid amide hydroxamic acid TACE inhibitors |
-
2000
- 2000-01-26 AR ARP000100322A patent/AR022422A1/es not_active Application Discontinuation
- 2000-01-27 DE DE60009035T patent/DE60009035T2/de not_active Expired - Fee Related
- 2000-01-27 EA EA200100805A patent/EA200100805A1/ru unknown
- 2000-01-27 EP EP00913263A patent/EP1147102B1/en not_active Expired - Lifetime
- 2000-01-27 NZ NZ512368A patent/NZ512368A/en unknown
- 2000-01-27 HU HU0105434A patent/HUP0105434A3/hu unknown
- 2000-01-27 IL IL14434600A patent/IL144346A0/xx unknown
- 2000-01-27 AU AU34739/00A patent/AU769182B2/en not_active Ceased
- 2000-01-27 BR BR0007726-7A patent/BR0007726A/pt not_active IP Right Cessation
- 2000-01-27 JP JP2000595996A patent/JP2002535399A/ja active Pending
- 2000-01-27 KR KR1020017009431A patent/KR20010101731A/ko not_active Application Discontinuation
- 2000-01-27 WO PCT/US2000/001980 patent/WO2000044740A2/en active IP Right Grant
- 2000-01-27 CZ CZ20012708A patent/CZ20012708A3/cs unknown
- 2000-01-27 CA CA002356481A patent/CA2356481A1/en not_active Abandoned
- 2000-01-27 CN CNB008030189A patent/CN1144785C/zh not_active Expired - Fee Related
- 2000-01-27 PL PL00349768A patent/PL349768A1/xx not_active Application Discontinuation
- 2000-01-27 DK DK00913263T patent/DK1147102T3/da active
- 2000-01-27 ES ES00913263T patent/ES2215621T3/es not_active Expired - Lifetime
- 2000-01-27 AT AT00913263T patent/ATE261955T1/de not_active IP Right Cessation
- 2000-01-27 PT PT00913263T patent/PT1147102E/pt unknown
-
2001
- 2001-06-18 ZA ZA200104981A patent/ZA200104981B/en unknown
- 2001-07-26 NO NO20013681A patent/NO20013681D0/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| HUP0105434A2 (en) | 2002-06-29 |
| DK1147102T3 (da) | 2004-06-01 |
| AR022422A1 (es) | 2002-09-04 |
| PT1147102E (pt) | 2004-07-30 |
| AU3473900A (en) | 2000-08-18 |
| DE60009035T2 (de) | 2005-03-31 |
| PL349768A1 (en) | 2002-09-09 |
| HUP0105434A3 (en) | 2002-08-28 |
| IL144346A0 (en) | 2002-05-23 |
| NO20013681L (no) | 2001-07-26 |
| EA200100805A1 (ru) | 2002-02-28 |
| NZ512368A (en) | 2003-11-28 |
| NO20013681D0 (no) | 2001-07-26 |
| EP1147102B1 (en) | 2004-03-17 |
| CN1144785C (zh) | 2004-04-07 |
| CN1337949A (zh) | 2002-02-27 |
| EP1147102A2 (en) | 2001-10-24 |
| DE60009035D1 (de) | 2004-04-22 |
| CA2356481A1 (en) | 2000-08-03 |
| CZ20012708A3 (cs) | 2002-04-17 |
| ATE261955T1 (de) | 2004-04-15 |
| KR20010101731A (ko) | 2001-11-14 |
| ES2215621T3 (es) | 2004-10-16 |
| WO2000044740A2 (en) | 2000-08-03 |
| JP2002535399A (ja) | 2002-10-22 |
| AU769182B2 (en) | 2004-01-15 |
| WO2000044740A3 (en) | 2001-01-25 |
| BR0007726A (pt) | 2001-10-30 |
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