SK282661B6 - Trisubstituované fenylové deriváty a farmaceutické prostriedky s ich obsahom - Google Patents
Trisubstituované fenylové deriváty a farmaceutické prostriedky s ich obsahom Download PDFInfo
- Publication number
- SK282661B6 SK282661B6 SK1630-96A SK163096A SK282661B6 SK 282661 B6 SK282661 B6 SK 282661B6 SK 163096 A SK163096 A SK 163096A SK 282661 B6 SK282661 B6 SK 282661B6
- Authority
- SK
- Slovakia
- Prior art keywords
- pyridine
- cyclopentyloxy
- methoxyphenyl
- ethyl
- group
- Prior art date
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- -1 Tri-substituted phenyl Chemical class 0.000 title claims abstract description 38
- XINQFOMFQFGGCQ-UHFFFAOYSA-L (2-dodecoxy-2-oxoethyl)-[6-[(2-dodecoxy-2-oxoethyl)-dimethylazaniumyl]hexyl]-dimethylazanium;dichloride Chemical compound [Cl-].[Cl-].CCCCCCCCCCCCOC(=O)C[N+](C)(C)CCCCCC[N+](C)(C)CC(=O)OCCCCCCCCCCCC XINQFOMFQFGGCQ-UHFFFAOYSA-L 0.000 title 1
- 239000000825 pharmaceutical preparation Substances 0.000 title 1
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 6
- 150000001875 compounds Chemical class 0.000 claims description 105
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 68
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 35
- 150000003839 salts Chemical class 0.000 claims description 20
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
- 125000000217 alkyl group Chemical group 0.000 claims description 10
- 125000005843 halogen group Chemical group 0.000 claims description 8
- 125000001424 substituent group Chemical group 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- 239000000126 substance Substances 0.000 claims description 7
- 125000002950 monocyclic group Chemical group 0.000 claims description 6
- 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 5
- 125000005842 heteroatom Chemical group 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 150000001204 N-oxides Chemical class 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- 125000003545 alkoxy 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
- 150000004677 hydrates Chemical class 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 239000001301 oxygen Substances 0.000 claims description 4
- 239000012453 solvate Substances 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 239000011593 sulfur Chemical group 0.000 claims description 4
- YFDLEUQNRUCUKQ-UHFFFAOYSA-N 4-[2-(3-cyclopentyloxy-4-methoxyphenyl)ethyl]-3-(2-phenylethyl)pyridine Chemical class C1=C(OC2CCCC2)C(OC)=CC=C1CCC1=CC=NC=C1CCC1=CC=CC=C1 YFDLEUQNRUCUKQ-UHFFFAOYSA-N 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000004076 pyridyl group Chemical group 0.000 claims description 3
- GQFPQTZBNQKKCC-UHFFFAOYSA-N 4-[2-(3-cyclopentyloxy-4-methoxyphenyl)-2-(4-phenylmethoxyphenyl)ethyl]pyridine Chemical compound COC1=CC=C(C(CC=2C=CN=CC=2)C=2C=CC(OCC=3C=CC=CC=3)=CC=2)C=C1OC1CCCC1 GQFPQTZBNQKKCC-UHFFFAOYSA-N 0.000 claims description 2
- SKIMLNLPEKUQLS-UHFFFAOYSA-N 4-[2-(3-cyclopentyloxy-4-methoxyphenyl)ethenyl]-3-(2-phenylethyl)pyridine Chemical class C1=C(OC2CCCC2)C(OC)=CC=C1C=CC1=CC=NC=C1CCC1=CC=CC=C1 SKIMLNLPEKUQLS-UHFFFAOYSA-N 0.000 claims description 2
- AOUHLICOKXHABK-UHFFFAOYSA-N 4-[4-[1-(3-cyclopentyloxy-4-methoxyphenyl)-2-pyridin-4-ylethyl]phenoxy]aniline Chemical class COC1=CC=C(C(CC=2C=CN=CC=2)C=2C=CC(OC=3C=CC(N)=CC=3)=CC=2)C=C1OC1CCCC1 AOUHLICOKXHABK-UHFFFAOYSA-N 0.000 claims description 2
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000001188 haloalkyl group Chemical group 0.000 claims description 2
- NUIVIVXBBBZCFA-UHFFFAOYSA-N n-[4-[4-[1-(3-cyclopentyloxy-4-methoxyphenyl)-2-pyridin-4-ylethoxy]phenyl]phenyl]methanesulfonamide Chemical compound COC1=CC=C(C(CC=2C=CN=CC=2)OC=2C=CC(=CC=2)C=2C=CC(NS(C)(=O)=O)=CC=2)C=C1OC1CCCC1 NUIVIVXBBBZCFA-UHFFFAOYSA-N 0.000 claims description 2
- IHAWMDKBKODHDR-UHFFFAOYSA-N n-[4-[4-[1-(3-cyclopentyloxy-4-methoxyphenyl)-2-pyridin-4-ylethyl]phenoxy]phenyl]acetamide Chemical class COC1=CC=C(C(CC=2C=CN=CC=2)C=2C=CC(OC=3C=CC(NC(C)=O)=CC=3)=CC=2)C=C1OC1CCCC1 IHAWMDKBKODHDR-UHFFFAOYSA-N 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- 125000002947 alkylene group Chemical group 0.000 claims 1
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- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 25
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- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 12
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 11
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- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
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- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
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- TYNSUEXNGLNQSS-UHFFFAOYSA-N 6-carbamoyl-5-hydroxy-4-methoxy-7,8-dihydro-3h-pyrrolo[3,2-e]indole-2-carboxylic acid Chemical compound C1=2C=C(C(O)=O)NC=2C(OC)=C(O)C2=C1CCN2C(N)=O TYNSUEXNGLNQSS-UHFFFAOYSA-N 0.000 description 3
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- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
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- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
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- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
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- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
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- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
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- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-M toluenesulfonate group Chemical group C=1(C(=CC=CC1)S(=O)(=O)[O-])C LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
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- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
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- JEJAMASKDTUEBZ-UHFFFAOYSA-N tris(1,1,3-tribromo-2,2-dimethylpropyl) phosphate Chemical compound BrCC(C)(C)C(Br)(Br)OP(=O)(OC(Br)(Br)C(C)(C)CBr)OC(Br)(Br)C(C)(C)CBr JEJAMASKDTUEBZ-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- 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
- C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
- C07D213/30—Oxygen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyridine Compounds (AREA)
- Lock And Its Accessories (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9412385A GB9412385D0 (en) | 1994-06-21 | 1994-06-21 | Chemical compounds |
| GB9412492A GB9412492D0 (en) | 1994-06-22 | 1994-06-22 | Chemical compounds |
| PCT/GB1995/001459 WO1995035281A1 (en) | 1994-06-21 | 1995-06-21 | Tri-substituted phenyl derivates useful as pde iv inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| SK163096A3 SK163096A3 (en) | 1997-10-08 |
| SK282661B6 true SK282661B6 (sk) | 2002-11-06 |
Family
ID=26305090
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK1630-96A SK282661B6 (sk) | 1994-06-21 | 1995-06-21 | Trisubstituované fenylové deriváty a farmaceutické prostriedky s ich obsahom |
Country Status (18)
| Country | Link |
|---|---|
| US (2) | US5786354A (cs) |
| EP (1) | EP0770065B1 (cs) |
| JP (1) | JP3856465B2 (cs) |
| CN (1) | CN1304372C (cs) |
| AT (1) | ATE263153T1 (cs) |
| AU (1) | AU707472B2 (cs) |
| CZ (1) | CZ293311B6 (cs) |
| DE (1) | DE69532808T2 (cs) |
| DK (1) | DK0770065T3 (cs) |
| ES (1) | ES2218548T3 (cs) |
| FI (1) | FI115302B (cs) |
| HU (1) | HUT76803A (cs) |
| NO (1) | NO312672B1 (cs) |
| NZ (1) | NZ288294A (cs) |
| PT (1) | PT770065E (cs) |
| RU (1) | RU2201921C2 (cs) |
| SK (1) | SK282661B6 (cs) |
| WO (1) | WO1995035281A1 (cs) |
Families Citing this family (84)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9222253D0 (en) * | 1992-10-23 | 1992-12-09 | Celltech Ltd | Chemical compounds |
| GB9304919D0 (en) * | 1993-03-10 | 1993-04-28 | Celltech Ltd | Chemical compounds |
| GB9304920D0 (en) * | 1993-03-10 | 1993-04-28 | Celltech Ltd | Chemical compounds |
| WO1995017399A1 (en) * | 1993-12-22 | 1995-06-29 | Celltech Therapeutics Limited | Trisubstituted phenyl derivatives, processes for their preparation and their use as phosphodiesterase (type iv) inhibitors |
| US5786354A (en) * | 1994-06-21 | 1998-07-28 | Celltech Therapeutics, Limited | Tri-substituted phenyl derivatives and processes for their preparation |
| US6245774B1 (en) | 1994-06-21 | 2001-06-12 | Celltech Therapeutics Limited | Tri-substituted phenyl or pyridine derivatives |
| GB9412571D0 (en) | 1994-06-22 | 1994-08-10 | Celltech Ltd | Chemical compounds |
| GB9412573D0 (en) | 1994-06-22 | 1994-08-10 | Celltech Ltd | Chemical compounds |
| GB9523675D0 (en) | 1995-11-20 | 1996-01-24 | Celltech Therapeutics Ltd | Chemical compounds |
| WO1997022586A1 (en) * | 1995-12-15 | 1997-06-26 | Merck Frosst Canada Inc. | Tri-aryl ethane derivatives as pde iv inhibitors |
| US5710170A (en) * | 1995-12-15 | 1998-01-20 | Merck Frosst Canada, Inc. | Tri-aryl ethane derivatives as PDE IV inhibitors |
| GB9526245D0 (en) * | 1995-12-21 | 1996-02-21 | Celltech Therapeutics Ltd | Chemical compounds |
| GB9526246D0 (en) * | 1995-12-21 | 1996-02-21 | Celltech Therapeutics Ltd | Chemical compounds |
| GB9526243D0 (en) * | 1995-12-21 | 1996-02-21 | Celltech Therapeutics Ltd | Chemical compounds |
| DE19605766A1 (de) * | 1996-02-16 | 1997-08-21 | Basf Ag | Substituierte 2-Phenylpyridine |
| GB9608435D0 (en) * | 1996-04-24 | 1996-06-26 | Celltech Therapeutics Ltd | Chemical compounds |
| GB9619284D0 (en) * | 1996-09-16 | 1996-10-30 | Celltech Therapeutics Ltd | Chemical compounds |
| GB9622363D0 (en) | 1996-10-28 | 1997-01-08 | Celltech Therapeutics Ltd | Chemical compounds |
| GB9625184D0 (en) * | 1996-12-04 | 1997-01-22 | Celltech Therapeutics Ltd | Chemical compounds |
| JP2001507349A (ja) * | 1996-12-23 | 2001-06-05 | セルテック セラピューティックス リミテッド | 縮合多環式２−アミノピリミジン誘導体、それらの製造およびたんぱく質チロシンキナーゼ抑制因子としてのそれらの使用 |
| GB9705361D0 (en) * | 1997-03-14 | 1997-04-30 | Celltech Therapeutics Ltd | Chemical compounds |
| GB9713087D0 (en) * | 1997-06-20 | 1997-08-27 | Celltech Therapeutics Ltd | Chemical compounds |
| US6180650B1 (en) * | 1999-04-23 | 2001-01-30 | Merck Frosst Canada & Co. | Heterosubstituted pyridine derivatives as PDE 4 inhibitors |
| GB9914258D0 (en) | 1999-06-18 | 1999-08-18 | Celltech Therapeutics Ltd | Chemical compounds |
| TR200201317T2 (tr) | 1999-08-21 | 2002-11-21 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Sinerjistik kombinasyon. |
| EP1229934B1 (en) | 1999-10-01 | 2014-03-05 | Immunogen, Inc. | Compositions and methods for treating cancer using immunoconjugates and chemotherapeutic agents |
| GB9924862D0 (en) * | 1999-10-20 | 1999-12-22 | Celltech Therapeutics Ltd | Chemical compounds |
| US6410563B1 (en) | 1999-12-22 | 2002-06-25 | Merck Frosst Canada & Co. | Substituted 8-arylquinoline phosphodiesterase-4 inhibitors |
| US6639077B2 (en) | 2000-03-23 | 2003-10-28 | Merck Frosst Canada & Co. | Tri-aryl-substituted-ethane PDE4 inhibitors |
| MY123585A (en) * | 2000-03-23 | 2006-05-31 | Merck Canada Inc | Tri-aryl-substituted-ethane pde4 inhibitors. |
| JP2003534328A (ja) | 2000-05-25 | 2003-11-18 | メルク フロスト カナダ アンド カンパニー | フルオロアルコキシ置換ベンズアミドジクロロピリジニルｎ−オキシドｐｄｅ４阻害剤 |
| US6740666B2 (en) | 2000-12-20 | 2004-05-25 | Merck & Co., Inc. | Substituted 8-arylquinoline phosphodiesterase-4 inhibitors |
| US6699890B2 (en) | 2000-12-22 | 2004-03-02 | Memory Pharmaceuticals Corp. | Phosphodiesterase 4 inhibitors |
| DE10064997A1 (de) | 2000-12-23 | 2002-06-27 | Merck Patent Gmbh | Benzoylpyridazine |
| US7153871B2 (en) * | 2001-01-22 | 2006-12-26 | Memory Pharmaceuticals Corporation | Phosphodiesterase 4 inhibitors, including aminoindazole and aminobenzofuran analogs |
| US7205320B2 (en) * | 2001-01-22 | 2007-04-17 | Memory Pharmaceuticals Corp. | Phosphodiesterase 4 inhibitors |
| CA2447765C (en) | 2001-05-24 | 2011-01-25 | Merck Frosst Canada & Co./Merck Frosst Canada & Cie | 1-biaryl-1,8-napthyridin-4-one phosphodiesterase-4 inhibitors |
| MXPA03010810A (es) * | 2001-05-29 | 2004-03-22 | Schering Ag | Pirimidinas inhibidoras de cdk, su obtencion y su uso como medicamentos. |
| JO2311B1 (en) | 2001-08-29 | 2005-09-12 | ميرك فروست كندا ليمتد | Alkyl inhibitors Ariel phosphodiesterase-4 |
| DE10150517A1 (de) * | 2001-10-12 | 2003-04-17 | Merck Patent Gmbh | Verwendung von Phosphodiesterase IV-Inhibitoren |
| CA2492911A1 (en) * | 2002-07-19 | 2004-01-29 | Memory Pharmaceuticals Corporation | 6-amino-1h-indazole and 4-aminobenzofuran compounds as phosphodiesterase 4 inhibitors |
| HRP20050083A2 (en) | 2002-07-19 | 2005-08-31 | Memory Pharmaceuticals Corporation | Phosphodiesterase 4 inhibitors, including n-substituted aniline and diphenylamine analogs |
| ATE481387T1 (de) * | 2002-11-19 | 2010-10-15 | Memory Pharm Corp | Pyridin-n-oxidverbindungen alsphosphodiesterase-4-inhibitoren |
| US7772188B2 (en) | 2003-01-28 | 2010-08-10 | Ironwood Pharmaceuticals, Inc. | Methods and compositions for the treatment of gastrointestinal disorders |
| US7153824B2 (en) | 2003-04-01 | 2006-12-26 | Applied Research Systems Ars Holding N.V. | Inhibitors of phosphodiesterases in infertility |
| DE10344742A1 (de) | 2003-09-25 | 2005-04-14 | Endress + Hauser Flowtec Ag, Reinach | Verfahren zum Einstellen einer mechanischen Resonanzfrequenz |
| MY141255A (en) * | 2003-12-11 | 2010-03-31 | Memory Pharm Corp | Phosphodiesterase 4 inhibitors, including n-substituted diarylamine analogs |
| MX2007004488A (es) * | 2004-10-13 | 2007-09-11 | Wyeth Corp | Analogos de anilino-pirimidina n-bencenosulfonilo sustituidos. |
| WO2007025177A2 (en) | 2005-08-26 | 2007-03-01 | Braincells, Inc. | Neurogenesis by muscarinic receptor modulation |
| EP2258357A3 (en) | 2005-08-26 | 2011-04-06 | Braincells, Inc. | Neurogenesis with acetylcholinesterase inhibitor |
| CA2625153A1 (en) | 2005-10-21 | 2007-04-26 | Braincells, Inc. | Modulation of neurogenesis by pde inhibition |
| JP2009513672A (ja) | 2005-10-31 | 2009-04-02 | ブレインセルス，インコーポレイティド | 神経発生のｇａｂａ受容体媒介調節 |
| US20100216734A1 (en) | 2006-03-08 | 2010-08-26 | Braincells, Inc. | Modulation of neurogenesis by nootropic agents |
| EP2382975A3 (en) | 2006-05-09 | 2012-02-29 | Braincells, Inc. | Neurogenesis by modulating angiotensin |
| EP2026813A2 (en) | 2006-05-09 | 2009-02-25 | Braincells, Inc. | 5 ht receptor mediated neurogenesis |
| DE602007012105D1 (de) * | 2006-07-14 | 2011-03-03 | Chiesi Farma Spa | Derivate von 1-phenyl-2-pyridinylalkylenalkohole als phosphodiesteraseinhibitoren |
| MX2009002496A (es) | 2006-09-08 | 2009-07-10 | Braincells Inc | Combinaciones que contienen un derivado de 4-acilaminopiridina. |
| US20100184806A1 (en) | 2006-09-19 | 2010-07-22 | Braincells, Inc. | Modulation of neurogenesis by ppar agents |
| AU2008261102B2 (en) | 2007-06-04 | 2013-11-28 | Bausch Health Ireland Limited | Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders |
| US8969514B2 (en) | 2007-06-04 | 2015-03-03 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases |
| EP2022783A1 (en) | 2007-08-08 | 2009-02-11 | CHIESI FARMACEUTICI S.p.A. | "Derivatives of 1-phenyl-2-pyridinyl alkyl alcohols as phosphodiesterase inhibitors" |
| EP2070913A1 (en) | 2007-12-14 | 2009-06-17 | CHIESI FARMACEUTICI S.p.A. | Ester derivatives as phosphodiesterase inhibitors |
| JP2011522828A (ja) | 2008-06-04 | 2011-08-04 | シナジー ファーマシューティカルズ インコーポレイテッド | 胃腸障害、炎症、癌、およびその他の障害の治療のために有用なグアニル酸シクラーゼのアゴニスト |
| US20100029689A1 (en) * | 2008-07-02 | 2010-02-04 | Memory Pharmaceuticals Corporation | Phosphodiesterase 4 inhibitors |
| WO2010009319A2 (en) | 2008-07-16 | 2010-01-21 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal, inflammation, cancer and other disorders |
| EP2196465A1 (en) | 2008-12-15 | 2010-06-16 | Almirall, S.A. | (3-oxo)pyridazin-4-ylurea derivatives as PDE4 inhibitors |
| US20100216805A1 (en) | 2009-02-25 | 2010-08-26 | Braincells, Inc. | Modulation of neurogenesis using d-cycloserine combinations |
| EP2226323A1 (en) | 2009-02-27 | 2010-09-08 | Almirall, S.A. | New tetrahydropyrazolo[3,4-c]isoquinolin-5-amine derivatives |
| EP2380890A1 (en) | 2010-04-23 | 2011-10-26 | Almirall, S.A. | New 7,8-dihydro-1,6-naphthyridin-5(6h)-one-derivatives as PDE4 inhibitors |
| EP2394998A1 (en) | 2010-05-31 | 2011-12-14 | Almirall, S.A. | 3-(5-Amino-6-oxo-1,6-dihydropyridazin-3-yl)-biphenyl derivatives as PDE4 inhibitors |
| US9616097B2 (en) | 2010-09-15 | 2017-04-11 | Synergy Pharmaceuticals, Inc. | Formulations of guanylate cyclase C agonists and methods of use |
| KR102034748B1 (ko) | 2011-03-01 | 2019-10-21 | 시너지 파마슈티컬즈 인코포레이티드 | 구아닐레이트 사이클라제 c 작용제의 제조 방법 |
| JP2014518203A (ja) | 2011-06-06 | 2014-07-28 | キエスィ ファルマチェウティチ エス．ピー．エー． | ホスホジエステラーゼ阻害剤としての１−フェニル−２−ピリジニルアルキルアルコール誘導体 |
| EP2760838B1 (en) | 2011-09-26 | 2017-05-10 | Chiesi Farmaceutici S.p.A. | Derivatives of 1-phenyl-2-pyridinyl alkyl alcohols as phosphodiesterase inhibitors |
| BR112014009471A2 (pt) | 2011-10-21 | 2017-04-18 | Chiesi Farm Spa | compostos, combinação de um composto, composição farmacêutica, uso de um composto, dispositivo e kit |
| US20150119399A1 (en) | 2012-01-10 | 2015-04-30 | President And Fellows Of Harvard College | Beta-cell replication promoting compounds and methods of their use |
| IN2014DN10239A (cs) | 2012-06-04 | 2015-08-07 | Chiesi Farma Spa | |
| CA2893628C (en) | 2012-12-05 | 2021-11-30 | Chiesi Farmaceutici S.P.A. | 1-phenyl-2-pyridinyl alkyl alcohol derivatives as phosphodiesterase inhibitors |
| HK1218629A1 (zh) | 2013-02-25 | 2017-03-03 | Bausch Health Ireland Limited | 用於结肠清洁的鸟苷酸环化酶受体激动剂 |
| EP2970384A1 (en) | 2013-03-15 | 2016-01-20 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase and their uses |
| HK1220611A1 (zh) | 2013-03-15 | 2017-05-12 | Bausch Health Ireland Limited | 用於治療胃腸道病症的組成物 |
| CN113388007A (zh) | 2013-06-05 | 2021-09-14 | 博士医疗爱尔兰有限公司 | 鸟苷酸环化酶c的超纯激动剂、制备和使用所述激动剂的方法 |
| WO2015021358A2 (en) | 2013-08-09 | 2015-02-12 | Dominique Charmot | Compounds and methods for inhibiting phosphate transport |
| WO2020237096A1 (en) | 2019-05-21 | 2020-11-26 | Ardelyx, Inc. | Combination for lowering serum phosphate in a patient |
Family Cites Families (87)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR1285932A (fr) * | 1960-12-26 | 1962-03-02 | Nord Aviation | Charge creuse |
| US3947467A (en) * | 1973-08-02 | 1976-03-30 | Eli Lilly And Company | 3-(5-Nitro-2-imidazolyl) pyrazoles |
| FR2257272B1 (cs) * | 1974-01-15 | 1978-08-25 | Pharmascience Labo | |
| DE2413935A1 (de) * | 1974-03-20 | 1975-10-16 | Schering Ag | 4-(polyalkoxy-phenyl)-2-pyrrolidone |
| US4193926A (en) * | 1974-03-20 | 1980-03-18 | Schering Aktiengesellschaft | 4-(Polyalkoxy phenyl)-2-pyrrolidones |
| DE2541855A1 (de) * | 1975-09-18 | 1977-03-31 | Schering Ag | 4-(polyalkoxy-phenyl)-2-pyrrolidone ii |
| FR2313422A2 (fr) * | 1975-06-02 | 1976-12-31 | Labaz | Nouveaux stabilisants des polymeres et copolymeres du chlorure de vinyle |
| SU888821A3 (ru) * | 1976-12-03 | 1981-12-07 | Шеринг Аг (Инофирма) | Способ получени 5-(замещенный фенил)-оксазолидинонов или их серусодержащих аналогов |
| ATE798T1 (de) * | 1978-06-15 | 1982-04-15 | Imperial Chemical Industries Plc | Entzuendungshemmende 1-phe nyl-2-aminoaethanol-derivate, verfahren zu ihrer herstellung und sie enthaltende pharmazeutische zusammensetzungen zur oertlichen anwendung. |
| EP0112707B1 (en) * | 1982-12-23 | 1987-11-04 | Smith Kline & French Laboratories Limited | Aminopyrimidinone derivatives as histamine h1-antagonists |
| IT1161221B (it) * | 1983-04-21 | 1987-03-18 | Ripharm Srl | Composto per il trattamento della psoriasi |
| US4694009A (en) * | 1984-06-25 | 1987-09-15 | Ciba-Geigy Corporation | Pesticidal compositions |
| DE3751742T3 (de) * | 1986-01-13 | 2002-11-21 | American Cyanamid Co., Wayne | 4,5,6-Substituierte 2-Pyrimidinamine |
| US4788195A (en) * | 1986-01-13 | 1988-11-29 | American Cyanamid Company | 4,5,6-substituted-N-(substituted-phenyl)-2-pyrimidinamines |
| US4876252A (en) * | 1986-01-13 | 1989-10-24 | American Cyanamid Company | 4,5,6-substituted-N-(substituted-phenyl)-2-pyrimidinamines |
| FI875724A0 (fi) * | 1986-04-29 | 1987-12-28 | Pfizer | Av kalcium oberoende camp fosfodiesteras-inhibitordepressant. |
| US5128358A (en) * | 1988-01-19 | 1992-07-07 | Pfizer Inc. | Aryl substituted nitrogen heterocyclic antidepressants |
| US4792561A (en) * | 1986-05-29 | 1988-12-20 | Syntex (U.S.A.) Inc. | Carbostyril derivatives as combined thromboxane synthetase and cyclic-AMP phosphodiesterase inhibitors |
| US4921862A (en) * | 1986-05-29 | 1990-05-01 | Syntex (U.S.A.) Inc. | Carbostyril derivatives as combined thromboxane synthetase and cyclic-amp phosphodiesterase inhibitors |
| CN1030415A (zh) * | 1987-02-20 | 1989-01-18 | 山之内制药株式会社 | 饱和的杂环碳酰胺衍生物和它的制备方法 |
| US4971959A (en) * | 1987-04-14 | 1990-11-20 | Warner-Lambert Company | Trisubstituted phenyl analogs having activity for congestive heart failure |
| US5274002A (en) * | 1987-04-14 | 1993-12-28 | Warner-Lambert Company | Trisubstituted phenyl analogs having activity for congestive heart failure |
| EP0295210B1 (de) * | 1987-06-11 | 1993-08-04 | Ciba-Geigy Ag | Mikrobizide |
| US4966622A (en) * | 1988-04-12 | 1990-10-30 | Ciba-Geigy Corporation | N-phenyl-N-pyrimidin-2-ylureas |
| US4897396A (en) * | 1988-06-03 | 1990-01-30 | Ciba-Geigy Corporation | 2-phenylamino pyrimidine derivatives and their uses as microbicides |
| AU640137B2 (en) * | 1989-04-17 | 1993-08-19 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Novel arylpyridazines, their manufacture, use and medicaments containing them |
| US5164372A (en) * | 1989-04-28 | 1992-11-17 | Fujisawa Pharmaceutical Company, Ltd. | Peptide compounds having substance p antagonism, processes for preparation thereof and pharmaceutical composition comprising the same |
| JPH075572B2 (ja) * | 1989-08-18 | 1995-01-25 | 積水化学工業株式会社 | ２―［２―（２―ヒドロキシフェニル）ビニルピラジンおよびその製造法 |
| JPH0377923A (ja) * | 1989-08-18 | 1991-04-03 | Sekisui Chem Co Ltd | 有機非線形光学材料 |
| DE4003919A1 (de) * | 1990-02-09 | 1991-08-14 | Basf Ag | Heteroarylalkene, verfahren und zwischenprodukte zu ihrer herstellung und ihre verwendung |
| GB9007762D0 (en) * | 1990-04-05 | 1990-06-06 | Beecham Group Plc | Novel compounds |
| WO1991016892A1 (en) * | 1990-04-27 | 1991-11-14 | Rorer International (Holdings), Inc. | Styryl compounds which inhibit egf receptor protein tyrosine kinase |
| IL98764A0 (en) * | 1990-07-10 | 1992-07-15 | Smithkline Beecham Corp | Oxamides |
| US5124455A (en) * | 1990-08-08 | 1992-06-23 | American Home Products Corporation | Oxime-carbamates and oxime-carbonates as bronchodilators and anti-inflammatory agents |
| NZ239946A (en) * | 1990-09-28 | 1994-09-27 | Smith Kline French Lab | 3-(tetrazol-5-yl)-6-(substituted phenyl)pyridine derivatives and medicaments |
| WO1992006963A1 (de) * | 1990-10-16 | 1992-04-30 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Arylpyridazinone |
| WO1992007567A1 (en) * | 1990-11-06 | 1992-05-14 | Smithkline Beecham Corporation | Imidazolidinone compounds |
| SE470395B (sv) * | 1990-12-05 | 1994-02-14 | Erik Lindgren Produktide Ab | Ryggstödjande anordning |
| GB9027055D0 (en) * | 1990-12-13 | 1991-02-06 | Sandoz Ltd | Organic compounds |
| US5698711A (en) * | 1991-01-28 | 1997-12-16 | Rhone-Poulenc Rorer Limited | Compounds containing phenyl linked to aryl or heteroaryl by an aliphatic- or heteroatom-containing linking group |
| IE71647B1 (en) * | 1991-01-28 | 1997-02-26 | Rhone Poulenc Rorer Ltd | Benzamide derivatives |
| WO1992019602A1 (de) * | 1991-04-26 | 1992-11-12 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Neue pyridazine |
| US5191084A (en) * | 1991-05-01 | 1993-03-02 | American Home Products Corporation | Phenyl pyrazolidinones as bronchodilators and anti-inflammatory agents |
| PT100441A (pt) * | 1991-05-02 | 1993-09-30 | Smithkline Beecham Corp | Pirrolidinonas, seu processo de preparacao, composicoes farmaceuticas que as contem e uso |
| EP0540165A1 (en) * | 1991-10-03 | 1993-05-05 | Zeneca Limited | Alkanoic acid derivatives |
| CA2080554A1 (en) * | 1991-10-15 | 1993-04-16 | Mitsubishi Chemical Corporation | Styrene derivatives |
| DE4136921A1 (de) * | 1991-11-11 | 1993-05-13 | Knoll Ag | Verfahren zur trennung von 5-methyl-tetrahydrofolsaeure |
| US5326898A (en) * | 1992-02-11 | 1994-07-05 | Allergan, Inc. | Substituted phenylethenyl compounds having retinoid-like biological activity |
| JP3195353B2 (ja) * | 1992-04-02 | 2001-08-06 | スミスクライン・ビーチャム・コーポレイション | 炎症疾患の治療および腫瘍壊死因子の産生阻害に有用な化合物 |
| TW225528B (cs) * | 1992-04-03 | 1994-06-21 | Ciba Geigy Ag | |
| US5521184A (en) * | 1992-04-03 | 1996-05-28 | Ciba-Geigy Corporation | Pyrimidine derivatives and processes for the preparation thereof |
| GB9212673D0 (en) * | 1992-06-15 | 1992-07-29 | Celltech Ltd | Chemical compounds |
| GB9212693D0 (en) * | 1992-06-15 | 1992-07-29 | Celltech Ltd | Chemical compounds |
| DK0652868T3 (da) * | 1992-07-28 | 2005-02-14 | Aventis Pharma Ltd | Hæmmere af c-AMP-phosphodiesterase |
| GB9222253D0 (en) * | 1992-10-23 | 1992-12-09 | Celltech Ltd | Chemical compounds |
| ATE234270T1 (de) * | 1992-12-02 | 2003-03-15 | Pfizer | Cathecoldiether als selektive pde iv hemmungsmittel |
| WO1994013661A1 (en) * | 1992-12-17 | 1994-06-23 | Pfizer Inc. | Substituted pyrazoles as crf antagonists |
| GB9226830D0 (en) * | 1992-12-23 | 1993-02-17 | Celltech Ltd | Chemical compounds |
| US5622977A (en) * | 1992-12-23 | 1997-04-22 | Celltech Therapeutics Limited | Tri-substituted (aryl or heteroaryl) derivatives and pharmaceutical compositions containing the same |
| TW263495B (cs) * | 1992-12-23 | 1995-11-21 | Celltech Ltd | |
| GB9304919D0 (en) * | 1993-03-10 | 1993-04-28 | Celltech Ltd | Chemical compounds |
| GB9304920D0 (en) * | 1993-03-10 | 1993-04-28 | Celltech Ltd | Chemical compounds |
| GB9315595D0 (en) * | 1993-07-28 | 1993-09-08 | Res Inst Medicine Chem | New compounds |
| CA2148931A1 (en) * | 1993-10-01 | 1995-04-13 | Jurg Zimmermann | Pyrimidineamine derivatives and processes for the preparation thereof |
| JP2983636B2 (ja) * | 1993-10-01 | 1999-11-29 | ノバルティス アクチェンゲゼルシャフト | 薬理学的に活性なピリジン誘導体及びその製造方法 |
| US5543520A (en) * | 1993-10-01 | 1996-08-06 | Ciba-Geigy Corporation | Pyrimidine derivatives |
| EP0672042B1 (en) * | 1993-10-01 | 2006-05-03 | Novartis AG | Pharmacologically active pyrimidineamine derivatives and processes for the preparation thereof |
| PL314605A1 (en) * | 1993-11-26 | 1996-09-16 | Pfizer | Isoxazolin compounds as anti-inflammatory agents |
| GB9326699D0 (en) * | 1993-12-22 | 1994-03-02 | Celltech Ltd | Chemical compounds |
| WO1995017399A1 (en) * | 1993-12-22 | 1995-06-29 | Celltech Therapeutics Limited | Trisubstituted phenyl derivatives, processes for their preparation and their use as phosphodiesterase (type iv) inhibitors |
| GB9326173D0 (en) * | 1993-12-22 | 1994-02-23 | Celltech Ltd | Chemical compounds and process |
| US5691376A (en) * | 1994-02-17 | 1997-11-25 | American Home Products Corporation | Substituted biphenyl derivatives |
| US5559137A (en) * | 1994-05-16 | 1996-09-24 | Smithkline Beecham Corp. | Compounds |
| JP3291299B2 (ja) * | 1994-06-06 | 2002-06-10 | ファイザー・インク | コルチコトロピン放出因子（ｃｒｆ）アンタゴニスト活性を有する置換ピラゾール |
| US5786354A (en) * | 1994-06-21 | 1998-07-28 | Celltech Therapeutics, Limited | Tri-substituted phenyl derivatives and processes for their preparation |
| US6245774B1 (en) * | 1994-06-21 | 2001-06-12 | Celltech Therapeutics Limited | Tri-substituted phenyl or pyridine derivatives |
| GB9412571D0 (en) * | 1994-06-22 | 1994-08-10 | Celltech Ltd | Chemical compounds |
| GB9412573D0 (en) * | 1994-06-22 | 1994-08-10 | Celltech Ltd | Chemical compounds |
| GB9412672D0 (en) * | 1994-06-23 | 1994-08-10 | Celltech Ltd | Chemical compounds |
| AU4270596A (en) * | 1994-12-23 | 1996-07-19 | Celltech Therapeutics Limited | Human phosphodiesterase type ivc, and its production and use |
| US5593997A (en) * | 1995-05-23 | 1997-01-14 | Pfizer Inc. | 4-aminopyrazolo(3-,4-D)pyrimidine and 4-aminopyrazolo-(3,4-D)pyridine tyrosine kinase inhibitors |
| PT856001E (pt) * | 1995-10-02 | 2003-01-31 | Hoffmann La Roche | Derivados de pirimidina enquanto antagonistas do receptor 5ht2c |
| GB9526245D0 (en) * | 1995-12-21 | 1996-02-21 | Celltech Therapeutics Ltd | Chemical compounds |
| GB9526243D0 (en) * | 1995-12-21 | 1996-02-21 | Celltech Therapeutics Ltd | Chemical compounds |
| GB9526246D0 (en) * | 1995-12-21 | 1996-02-21 | Celltech Therapeutics Ltd | Chemical compounds |
| GB9608435D0 (en) * | 1996-04-24 | 1996-06-26 | Celltech Therapeutics Ltd | Chemical compounds |
| GB9625184D0 (en) * | 1996-12-04 | 1997-01-22 | Celltech Therapeutics Ltd | Chemical compounds |
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1995
- 1995-06-20 US US08/492,639 patent/US5786354A/en not_active Expired - Fee Related
- 1995-06-21 NZ NZ288294A patent/NZ288294A/xx unknown
- 1995-06-21 RU RU97100794/04A patent/RU2201921C2/ru not_active IP Right Cessation
- 1995-06-21 WO PCT/GB1995/001459 patent/WO1995035281A1/en active IP Right Grant
- 1995-06-21 PT PT95922633T patent/PT770065E/pt unknown
- 1995-06-21 EP EP95922633A patent/EP0770065B1/en not_active Expired - Lifetime
- 1995-06-21 JP JP50184396A patent/JP3856465B2/ja not_active Expired - Fee Related
- 1995-06-21 SK SK1630-96A patent/SK282661B6/sk unknown
- 1995-06-21 DE DE1995632808 patent/DE69532808T2/de not_active Expired - Fee Related
- 1995-06-21 CN CNB951937405A patent/CN1304372C/zh not_active Expired - Fee Related
- 1995-06-21 ES ES95922633T patent/ES2218548T3/es not_active Expired - Lifetime
- 1995-06-21 CZ CZ19963730A patent/CZ293311B6/cs not_active IP Right Cessation
- 1995-06-21 AU AU27461/95A patent/AU707472B2/en not_active Ceased
- 1995-06-21 HU HU9603578A patent/HUT76803A/hu unknown
- 1995-06-21 DK DK95922633T patent/DK0770065T3/da active
- 1995-06-21 AT AT95922633T patent/ATE263153T1/de not_active IP Right Cessation
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1996
- 1996-12-19 FI FI965126A patent/FI115302B/fi active IP Right Grant
- 1996-12-20 NO NO19965524A patent/NO312672B1/no unknown
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1998
- 1998-03-26 US US09/048,592 patent/US6077854A/en not_active Expired - Fee Related
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| Publication number | Publication date |
|---|---|
| RU2201921C2 (ru) | 2003-04-10 |
| EP0770065A1 (en) | 1997-05-02 |
| CZ373096A3 (en) | 1997-08-13 |
| FI965126A7 (fi) | 1996-12-19 |
| JP3856465B2 (ja) | 2006-12-13 |
| FI965126A0 (fi) | 1996-12-19 |
| CN1304372C (zh) | 2007-03-14 |
| AU707472B2 (en) | 1999-07-08 |
| US5786354A (en) | 1998-07-28 |
| ATE263153T1 (de) | 2004-04-15 |
| DK0770065T3 (da) | 2004-07-19 |
| FI115302B (fi) | 2005-04-15 |
| NO312672B1 (no) | 2002-06-17 |
| US6077854A (en) | 2000-06-20 |
| NO965524L (no) | 1996-12-20 |
| DE69532808T2 (de) | 2005-01-13 |
| SK163096A3 (en) | 1997-10-08 |
| DE69532808D1 (de) | 2004-05-06 |
| CN1151732A (zh) | 1997-06-11 |
| HUT76803A (en) | 1997-11-28 |
| CZ293311B6 (cs) | 2004-03-17 |
| PT770065E (pt) | 2004-08-31 |
| AU2746195A (en) | 1996-01-15 |
| NZ288294A (en) | 1999-01-28 |
| JPH10503173A (ja) | 1998-03-24 |
| WO1995035281A1 (en) | 1995-12-28 |
| ES2218548T3 (es) | 2004-11-16 |
| EP0770065B1 (en) | 2004-03-31 |
| NO965524D0 (no) | 1996-12-20 |
| HU9603578D0 (en) | 1997-02-28 |
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