AU658887B2 - Pyridazinone acetic acids as aldose reductase inhibitors - Google Patents
Pyridazinone acetic acids as aldose reductase inhibitors Download PDFInfo
- Publication number
- AU658887B2 AU658887B2 AU17796/92A AU1779692A AU658887B2 AU 658887 B2 AU658887 B2 AU 658887B2 AU 17796/92 A AU17796/92 A AU 17796/92A AU 1779692 A AU1779692 A AU 1779692A AU 658887 B2 AU658887 B2 AU 658887B2
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- Australia
- Prior art keywords
- methyl
- compound
- hydrogen
- oxo
- dihydro
- 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.)
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- 239000003288 aldose reductase inhibitor Substances 0.000 title description 7
- 229940090865 aldose reductase inhibitors used in diabetes Drugs 0.000 title description 7
- JNRGNBBXGZMDOO-UHFFFAOYSA-N acetic acid;1h-pyridazin-6-one Chemical class CC(O)=O.O=C1C=CC=NN1 JNRGNBBXGZMDOO-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 133
- -1 C 4 alkyl Substances 0.000 claims description 90
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 49
- 239000002253 acid Substances 0.000 claims description 44
- 239000001257 hydrogen Substances 0.000 claims description 41
- 229910052739 hydrogen Inorganic materials 0.000 claims description 41
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 30
- 229910052794 bromium Inorganic materials 0.000 claims description 29
- 239000000460 chlorine Substances 0.000 claims description 27
- 229910052801 chlorine Inorganic materials 0.000 claims description 27
- 238000000034 method Methods 0.000 claims description 27
- 229910052731 fluorine Inorganic materials 0.000 claims description 26
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 26
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 25
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 25
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 24
- 239000011737 fluorine Substances 0.000 claims description 24
- 150000003839 salts Chemical class 0.000 claims description 23
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 14
- 239000000203 mixture Substances 0.000 claims description 14
- 229910052760 oxygen Inorganic materials 0.000 claims description 14
- 238000002360 preparation method Methods 0.000 claims description 14
- 229910052717 sulfur Inorganic materials 0.000 claims description 14
- 239000000651 prodrug Chemical group 0.000 claims description 13
- 229940002612 prodrug Drugs 0.000 claims description 13
- 102000016912 Aldehyde Reductase Human genes 0.000 claims description 12
- 108010053754 Aldehyde reductase Proteins 0.000 claims description 12
- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 claims description 12
- TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 claims description 12
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- 206010012601 diabetes mellitus Diseases 0.000 claims description 11
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- 125000001153 fluoro group Chemical group F* 0.000 claims description 10
- 150000002431 hydrogen Chemical class 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 9
- 230000000694 effects Effects 0.000 claims description 9
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- 125000004244 benzofuran-2-yl group Chemical group [H]C1=C(*)OC2=C([H])C([H])=C([H])C([H])=C12 0.000 claims description 6
- 125000004190 benzothiazol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N=C(*)SC2=C1[H] 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 6
- 239000002798 polar solvent Substances 0.000 claims description 5
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 claims description 4
- 241000124008 Mammalia Species 0.000 claims description 4
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 4
- 229910000037 hydrogen sulfide Inorganic materials 0.000 claims description 4
- 230000002401 inhibitory effect Effects 0.000 claims description 4
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- 229910052740 iodine Inorganic materials 0.000 claims description 3
- CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 claims description 3
- FGKJKXHYFUBOEW-UHFFFAOYSA-N 2-[6-[(5,7-difluoro-1,3-benzothiazol-2-yl)methyl]-3,4-dimethyl-5-oxo-1,6-dihydropyridazin-2-yl]acetic acid Chemical compound N1N(CC(O)=O)C(C)=C(C)C(=O)C1CC1=NC2=CC(F)=CC(F)=C2S1 FGKJKXHYFUBOEW-UHFFFAOYSA-N 0.000 claims description 2
- VRVRGVPWCUEOGV-UHFFFAOYSA-N 2-aminothiophenol Chemical class NC1=CC=CC=C1S VRVRGVPWCUEOGV-UHFFFAOYSA-N 0.000 claims description 2
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 2
- 125000001246 bromo group Chemical group Br* 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims 6
- 230000003301 hydrolyzing effect Effects 0.000 claims 4
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 claims 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 2
- 125000004505 1,2,4-oxadiazol-5-yl group Chemical group O1N=CN=C1* 0.000 claims 1
- HRCPYJCZKZQPTR-UHFFFAOYSA-N 2-[6-[(5,7-difluoro-1,3-benzothiazol-2-yl)methyl]-5-oxo-1,6-dihydropyridazin-2-yl]acetic acid Chemical compound O=C1C=CN(CC(=O)O)NC1CC1=NC2=CC(F)=CC(F)=C2S1 HRCPYJCZKZQPTR-UHFFFAOYSA-N 0.000 claims 1
- LEJDBIDQVYRDHI-UHFFFAOYSA-N 2-[6-[(5-bromo-1,3-benzoxazol-2-yl)methyl]-3,4-dimethyl-5-oxo-1,6-dihydropyridazin-2-yl]acetic acid Chemical compound N1N(CC(O)=O)C(C)=C(C)C(=O)C1CC1=NC2=CC(Br)=CC=C2O1 LEJDBIDQVYRDHI-UHFFFAOYSA-N 0.000 claims 1
- RWHJUYXIHVKMDK-UHFFFAOYSA-N 2-pyridazin-3-ylacetic acid Chemical compound OC(=O)CC1=CC=CN=N1 RWHJUYXIHVKMDK-UHFFFAOYSA-N 0.000 claims 1
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- 239000002168 alkylating agent Substances 0.000 claims 1
- 229940100198 alkylating agent Drugs 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- 229910052698 phosphorus Inorganic materials 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
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- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 23
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 19
- 238000006243 chemical reaction Methods 0.000 description 18
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- 239000000243 solution Substances 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
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- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
- 235000011054 acetic acid Nutrition 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- 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 7
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical group C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 7
- 230000001684 chronic effect Effects 0.000 description 7
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
- C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D237/10—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having 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
- C07D237/14—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/26—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/26—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings condensed with carbocyclic rings or ring systems
- C07D237/30—Phthalazines
- C07D237/32—Phthalazines with oxygen atoms directly attached to carbon atoms of the nitrogen-containing ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Diabetes (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US67691991A | 1991-03-28 | 1991-03-28 | |
| US676919 | 1991-03-28 | ||
| PCT/US1992/001603 WO1992017446A2 (en) | 1991-03-28 | 1992-03-09 | Pyridazinone acetic acids aldose reductase inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU1779692A AU1779692A (en) | 1992-11-02 |
| AU658887B2 true AU658887B2 (en) | 1995-05-04 |
Family
ID=24716565
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU17796/92A Ceased AU658887B2 (en) | 1991-03-28 | 1992-03-09 | Pyridazinone acetic acids as aldose reductase inhibitors |
Country Status (19)
| Country | Link |
|---|---|
| EP (1) | EP0582643A1 (enExample) |
| JP (1) | JPH06500793A (enExample) |
| CN (1) | CN1065269A (enExample) |
| AU (1) | AU658887B2 (enExample) |
| BR (1) | BR9205810A (enExample) |
| CA (1) | CA2107104A1 (enExample) |
| CZ (1) | CZ387092A3 (enExample) |
| DE (1) | DE9290035U1 (enExample) |
| FI (1) | FI934222L (enExample) |
| HU (1) | HUT67836A (enExample) |
| IE (1) | IE920979A1 (enExample) |
| IL (1) | IL101325A0 (enExample) |
| MX (1) | MX9201414A (enExample) |
| NZ (1) | NZ242152A (enExample) |
| PT (1) | PT100301A (enExample) |
| TW (1) | TW207998B (enExample) |
| WO (1) | WO1992017446A2 (enExample) |
| YU (1) | YU30392A (enExample) |
| ZA (1) | ZA922238B (enExample) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1236720B1 (en) | 2001-02-28 | 2005-06-15 | Pfizer Products Inc. | Sulfonyl pyridazinone compounds useful as aldose reductase inhibitors |
| SE0100873D0 (sv) * | 2001-03-13 | 2001-03-13 | Astrazeneca Ab | Method of treatment |
| YU71403A (sh) | 2001-03-30 | 2006-05-25 | Pfizer Products Inc. | Piridazinoni kao inhibitori aldoza reduktaze |
| AU761191B2 (en) * | 2001-05-24 | 2003-05-29 | Pfizer Products Inc. | Therapies for tissue damage resulting from ischemia |
| US7572910B2 (en) | 2003-02-20 | 2009-08-11 | Pfizer, Inc. | Pyridazinone aldose reductase inhibitors |
| CN111617072B (zh) * | 2019-02-27 | 2023-06-20 | 苏州凯祥生物科技有限公司 | 一种高尿酸血症药物组合物及用于治疗高尿酸血症的药物 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0676391B2 (ja) * | 1987-06-09 | 1994-09-28 | フアイザー・インコーポレイテツド | ベンゾチアゾール等の複素環側鎖を有するオキソフタラジニル酢酸類の製造方法 |
| FR2647676A1 (fr) * | 1989-06-05 | 1990-12-07 | Union Pharma Scient Appl | Nouveaux derives de pyridazinone, leurs procedes de preparation, medicaments les contenant, utiles notamment comme inhibiteurs de l'aldose reductase |
-
1992
- 1992-03-09 CA CA002107104A patent/CA2107104A1/en not_active Abandoned
- 1992-03-09 FI FI934222A patent/FI934222L/fi not_active Application Discontinuation
- 1992-03-09 HU HU9302728A patent/HUT67836A/hu unknown
- 1992-03-09 CZ CS923870A patent/CZ387092A3/cs unknown
- 1992-03-09 DE DE9290035U patent/DE9290035U1/de not_active Expired - Lifetime
- 1992-03-09 JP JP4509938A patent/JPH06500793A/ja active Pending
- 1992-03-09 AU AU17796/92A patent/AU658887B2/en not_active Ceased
- 1992-03-09 BR BR9205810A patent/BR9205810A/pt not_active Application Discontinuation
- 1992-03-09 WO PCT/US1992/001603 patent/WO1992017446A2/en not_active Ceased
- 1992-03-09 EP EP92910955A patent/EP0582643A1/en not_active Withdrawn
- 1992-03-13 TW TW081101914A patent/TW207998B/zh active
- 1992-03-22 IL IL101325A patent/IL101325A0/xx unknown
- 1992-03-26 PT PT100301A patent/PT100301A/pt not_active Application Discontinuation
- 1992-03-26 YU YU30392A patent/YU30392A/sh unknown
- 1992-03-27 CN CN92102224A patent/CN1065269A/zh active Pending
- 1992-03-27 MX MX9201414A patent/MX9201414A/es unknown
- 1992-03-27 NZ NZ24215292A patent/NZ242152A/en unknown
- 1992-03-27 IE IE097992A patent/IE920979A1/en not_active Application Discontinuation
- 1992-03-27 ZA ZA922238A patent/ZA922238B/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| IL101325A0 (en) | 1992-11-15 |
| PT100301A (pt) | 1993-06-30 |
| HU9302728D0 (en) | 1993-12-28 |
| ZA922238B (en) | 1993-09-27 |
| FI934222A0 (fi) | 1993-09-27 |
| CA2107104A1 (en) | 1992-09-29 |
| MX9201414A (es) | 1992-10-01 |
| BR9205810A (pt) | 1994-06-28 |
| YU30392A (sh) | 1994-11-15 |
| DE9290035U1 (de) | 1993-11-18 |
| CN1065269A (zh) | 1992-10-14 |
| FI934222A7 (fi) | 1993-09-27 |
| WO1992017446A3 (en) | 1992-11-26 |
| JPH06500793A (ja) | 1994-01-27 |
| TW207998B (enExample) | 1993-06-21 |
| IE920979A1 (en) | 1992-10-07 |
| WO1992017446A2 (en) | 1992-10-15 |
| AU1779692A (en) | 1992-11-02 |
| CZ387092A3 (en) | 1994-02-16 |
| FI934222L (fi) | 1993-09-27 |
| EP0582643A1 (en) | 1994-02-16 |
| NZ242152A (en) | 1994-07-26 |
| HUT67836A (en) | 1995-05-29 |
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