SK283300B6 - Piperidínové zlúčeniny s analgetickým účinkom, spôsob ich prípravy, medziprodukty na ich prípravu, ich použitie, diagnostické činidlo a farmaceutické kompozície s ich obsahom - Google Patents
Piperidínové zlúčeniny s analgetickým účinkom, spôsob ich prípravy, medziprodukty na ich prípravu, ich použitie, diagnostické činidlo a farmaceutické kompozície s ich obsahom Download PDFInfo
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no 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
- C07D211/56—Nitrogen atoms
- C07D211/58—Nitrogen atoms attached in position 4
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/041—Heterocyclic compounds
- A61K51/044—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins
- A61K51/0446—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/041—Heterocyclic compounds
- A61K51/044—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins
- A61K51/0455—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- 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]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no 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
- C07D207/14—Nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no 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
- C07D211/56—Nitrogen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2123/00—Preparations for testing in vivo
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Physics & Mathematics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Optics & Photonics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Neurology (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pyrrole Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE9604786A SE9604786D0 (sv) | 1996-12-20 | 1996-12-20 | New compounds |
| PCT/SE1997/002051 WO1998028270A1 (en) | 1996-12-20 | 1997-12-09 | Novel compounds with analgesic effect |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| SK76399A3 SK76399A3 (en) | 2000-01-18 |
| SK283300B6 true SK283300B6 (sk) | 2003-05-02 |
Family
ID=20405139
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK763-99A SK283300B6 (sk) | 1996-12-20 | 1997-12-09 | Piperidínové zlúčeniny s analgetickým účinkom, spôsob ich prípravy, medziprodukty na ich prípravu, ich použitie, diagnostické činidlo a farmaceutické kompozície s ich obsahom |
Country Status (31)
| Country | Link |
|---|---|
| US (3) | US6153626A (enExample) |
| EP (2) | EP0946510B1 (enExample) |
| JP (1) | JP2001507021A (enExample) |
| KR (1) | KR20000069600A (enExample) |
| CN (2) | CN1154635C (enExample) |
| AR (1) | AR010378A1 (enExample) |
| AT (1) | ATE266638T1 (enExample) |
| AU (1) | AU738002B2 (enExample) |
| BR (1) | BR9713785A (enExample) |
| CA (1) | CA2274117A1 (enExample) |
| CZ (1) | CZ220099A3 (enExample) |
| DE (1) | DE69729115T2 (enExample) |
| DK (1) | DK0946510T3 (enExample) |
| EE (1) | EE03966B1 (enExample) |
| ES (1) | ES2219783T3 (enExample) |
| HU (1) | HUP0000613A3 (enExample) |
| ID (1) | ID21662A (enExample) |
| IL (1) | IL130536A0 (enExample) |
| IS (1) | IS5078A (enExample) |
| MY (1) | MY132705A (enExample) |
| NO (1) | NO313632B1 (enExample) |
| NZ (1) | NZ336028A (enExample) |
| PL (1) | PL188945B1 (enExample) |
| PT (1) | PT946510E (enExample) |
| RU (1) | RU2193030C2 (enExample) |
| SE (1) | SE9604786D0 (enExample) |
| SK (1) | SK283300B6 (enExample) |
| TR (1) | TR199901411T2 (enExample) |
| UA (1) | UA54481C2 (enExample) |
| WO (1) | WO1998028270A1 (enExample) |
| ZA (1) | ZA9711049B (enExample) |
Families Citing this family (46)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE9504661D0 (sv) | 1995-12-22 | 1995-12-22 | Astra Pharma Inc | New compounds |
| US6974825B1 (en) | 1996-12-20 | 2005-12-13 | Astrazeneca Canada Inc. | Compounds with analgesic effect |
| TW548271B (en) * | 1996-12-20 | 2003-08-21 | Astra Pharma Inc | Novel piperidine derivatives having an exocyclic double bond with analgesic effects |
| SE9604786D0 (sv) | 1996-12-20 | 1996-12-20 | Astra Pharma Inc | New compounds |
| AU2003220725B2 (en) * | 1997-12-24 | 2006-06-01 | Ortho-Mcneil Pharmaceutical, Inc. | 4-[aryl(piperidin-4-yl)] aminobenzamides which bind to the delta-opioid receptor |
| WO1999033806A1 (en) * | 1997-12-24 | 1999-07-08 | Ortho-Mcneil Pharmaceutical, Inc. | 4-[aryl(piperidin-4-yl)] aminobenzamides which bind to the delta-opioid receptor |
| US6900228B1 (en) | 1998-03-10 | 2005-05-31 | Research Triangle Institute | Opiate compounds, methods of making and methods of use |
| AU756983B2 (en) * | 1998-03-10 | 2003-01-30 | Research Triangle Institute | Novel opiate compounds, methods of making and methods of use |
| US6436959B1 (en) | 1998-12-23 | 2002-08-20 | Ortho-Mcneil Pharmaceutical, Inc. | 4-[aryl(piperidin-4-yl)]aminobenzamides |
| SE9904673D0 (sv) | 1999-12-20 | 1999-12-20 | Astra Pharma Inc | Novel compounds |
| SE9904674D0 (sv) * | 1999-12-20 | 1999-12-20 | Astra Pharma Inc | Novel compounds |
| SE9904675D0 (sv) | 1999-12-20 | 1999-12-20 | Astra Pharma Inc | Novel compounds |
| EP1242421A1 (en) | 1999-12-22 | 2002-09-25 | Ortho-McNeil Pharmaceutical, Inc. | 4-[aryl(8-azabicyclo[3.2.1] octan-3-yl)] aminobenzoic acid derivatives |
| CA2400640A1 (en) * | 2000-02-18 | 2001-08-23 | Meiji Seika Kaisha, Ltd. | Phenoxyalkylamine derivatives useful as opioid .delta. receptor ligands |
| IL151550A0 (en) | 2000-03-03 | 2003-04-10 | Ortho Mcneil Pharm Inc | 3-(diarylmethylene)-8-azabicyclo [3.2.1] octane derivatives |
| CA2404280A1 (en) | 2000-03-24 | 2002-09-23 | Meiji Seika Kaisha, Ltd. | Diphenylalkylamine derivatives useful as opioid .delta. receptor agonists |
| SE0001209D0 (sv) | 2000-04-04 | 2000-04-04 | Astrazeneca Canada Inc | Novel compounds |
| AU2002234010A1 (en) * | 2000-12-14 | 2002-06-24 | Ortho-Mcneil Pharmaceutical, Inc. | Benzamidine derivatives |
| AU2002222879B2 (en) * | 2000-12-15 | 2006-02-02 | Astrazeneca Ab | New process for the preparation diaryl-4-amino-piperidinyl compounds |
| SE0101773D0 (sv) | 2001-05-18 | 2001-05-18 | Astrazeneca Ab | Novel compounds |
| SE0101771D0 (sv) * | 2001-05-18 | 2001-05-18 | Astrazeneca Ab | Novel compounds |
| US7229994B2 (en) | 2001-05-18 | 2007-06-12 | Astrazeneca Ab | 4(phenyl-piperazinyl-methyl) benzamide derivatives and their use for the treatment of pain anxiety or gastrointestinal disorders |
| SE0101770D0 (sv) * | 2001-05-18 | 2001-05-18 | Astrazeneca Ab | Novel compounds |
| SE0101769D0 (sv) * | 2001-05-18 | 2001-05-18 | Astrazeneca Ab | Novel compounds |
| EA006507B1 (ru) | 2001-10-15 | 2005-12-29 | Янссен Фармацевтика Н.В. | Новые замещенные 4-фенил-4-[1h-имидазол-2-ил] пиперидиновые производные и их применение в качестве селективных непептидных агонистов дельта-опиоидов |
| US7501417B2 (en) * | 2002-03-13 | 2009-03-10 | Janssen Pharmaceutica, N.V. | Aminocarbonyl-derivatives as novel inhibitors of histone deacetylase |
| EP2399903A1 (en) | 2002-05-24 | 2011-12-28 | Millennium Pharmaceuticals, Inc. | Ccr9 inhibitors and methods of use thereof |
| SE0203303D0 (sv) | 2002-11-07 | 2002-11-07 | Astrazeneca Ab | Novel Compounds |
| SE0203302D0 (sv) | 2002-11-07 | 2002-11-07 | Astrazeneca Ab | Novel Compounds |
| SE0203300D0 (sv) | 2002-11-07 | 2002-11-07 | Astrazeneca Ab | Novel Compounds |
| US7227035B2 (en) | 2002-11-18 | 2007-06-05 | Chemocentryx | Bis-aryl sulfonamides |
| US7741519B2 (en) | 2007-04-23 | 2010-06-22 | Chemocentryx, Inc. | Bis-aryl sulfonamides |
| PT1562940E (pt) | 2002-11-18 | 2007-07-23 | Chemocentryx Inc | Sulfonamidas de arilo. |
| US7420055B2 (en) | 2002-11-18 | 2008-09-02 | Chemocentryx, Inc. | Aryl sulfonamides |
| ES2314362T3 (es) * | 2003-01-16 | 2009-03-16 | Acadia Pharmaceuticals Inc. | Agonistas inversos selectivos de los receptores 2a o 2c de serotonina utilizados como agentes terapeuticos contra enfermedades neurodegenerativas. |
| EP1644373A1 (en) | 2003-06-27 | 2006-04-12 | Janssen Pharmaceutica N.V. | Tricyclic delta opioid modulators |
| WO2005075472A1 (en) | 2004-02-03 | 2005-08-18 | Janssen Pharmaceutica, N.V. | 3-(diheteroarylnethylene)-8-azabicyclo[3.2.1]octane and 3-(aryl)(heteroaryl)methylene)-8-azabicyclo[3.2.1]octane derivatives |
| HRP20120343T1 (hr) | 2004-08-02 | 2012-05-31 | Astrazeneca Ab | Derivati diarilmetil piperazina, njihovi pripravci i njihova uporaba |
| BRPI0513075A (pt) * | 2004-08-05 | 2008-04-22 | Janssen Pharmaceutica Nv | moduladores gama-opióides tricìclicos |
| AU2005319059A1 (en) * | 2004-12-22 | 2006-06-29 | Janssen Pharmaceutica N.V. | Tricyclic delta-opioid modulators |
| MX2007007626A (es) * | 2004-12-22 | 2008-01-28 | Johnson & Johnson | Moduladores delta-opioides triciclicos. |
| CA2592464A1 (en) * | 2004-12-22 | 2006-06-29 | Janssen Pharmaceutica N.V. | Tricyclic .delta.-opioid modulators |
| CA2594347A1 (en) * | 2005-01-06 | 2006-07-13 | Janssen Pharmaceutica N.V. | Tricyclic d-opioid modulators |
| TWI449692B (zh) | 2005-05-13 | 2014-08-21 | Otsuka Pharma Co Ltd | 吡咯烷化合物（三） |
| JP2008543866A (ja) * | 2005-06-16 | 2008-12-04 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | 三環式オピオイドモジュレーター |
| JP5219465B2 (ja) * | 2006-11-10 | 2013-06-26 | 大塚製薬株式会社 | 医薬 |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4091096A (en) * | 1976-03-19 | 1978-05-23 | Eli Lilly And Company | Dinitroanilines for the control of phytopathogens |
| EG12406A (en) * | 1976-08-12 | 1979-03-31 | Janssen Pharmaceutica Nv | Process for preparing of novel n-aryl-n-(1-l-4-piperidinyl)-arylacetamides |
| SE441448B (sv) * | 1977-05-23 | 1985-10-07 | Pfizer | Sett att framstella hexahydro-gamma-karbolinforeningar |
| DE3200304A1 (de) * | 1981-01-16 | 1982-08-26 | Sandoz-Patent-GmbH, 7850 Lörrach | 3-aminopropoxyaryl-derivate, ihre herstellung und sie enthaltende arzneimittel |
| DE3563964D1 (en) * | 1984-10-16 | 1988-09-01 | Synthelabo | Piperidine derivatives, their preparation and their therapeutical application |
| YU150489A (sh) | 1989-08-10 | 1992-12-21 | W.L. Gore & Co. Gmbh. | Uređaj za ispitivanje odevnih predmeta na nepromočivost |
| KR940003491B1 (ko) | 1989-08-10 | 1994-04-23 | 리히터 게데온 베기에스제티 기아르 알.티 | 4,4-이중 치환된 피페리딘 유도체와 그 제조방법 및 상기 화합물을 함유하는 약제학적 조성물 |
| SE8904298D0 (sv) * | 1989-12-21 | 1989-12-21 | Astra Ab | New compounds |
| GB9202238D0 (en) * | 1992-02-03 | 1992-03-18 | Wellcome Found | Compounds |
| US5854245A (en) * | 1996-06-28 | 1998-12-29 | Merck & Co., Inc. | Fibrinogen receptor antagonists |
| SE9604786D0 (sv) | 1996-12-20 | 1996-12-20 | Astra Pharma Inc | New compounds |
| TW548271B (en) * | 1996-12-20 | 2003-08-21 | Astra Pharma Inc | Novel piperidine derivatives having an exocyclic double bond with analgesic effects |
| WO1999033806A1 (en) * | 1997-12-24 | 1999-07-08 | Ortho-Mcneil Pharmaceutical, Inc. | 4-[aryl(piperidin-4-yl)] aminobenzamides which bind to the delta-opioid receptor |
| AU756983B2 (en) | 1998-03-10 | 2003-01-30 | Research Triangle Institute | Novel opiate compounds, methods of making and methods of use |
| US6436959B1 (en) | 1998-12-23 | 2002-08-20 | Ortho-Mcneil Pharmaceutical, Inc. | 4-[aryl(piperidin-4-yl)]aminobenzamides |
-
1996
- 1996-12-20 SE SE9604786A patent/SE9604786D0/xx unknown
-
1997
- 1997-09-12 UA UA99074131A patent/UA54481C2/uk unknown
- 1997-12-09 EE EEP199900261A patent/EE03966B1/xx not_active IP Right Cessation
- 1997-12-09 BR BR9713785-5A patent/BR9713785A/pt unknown
- 1997-12-09 EP EP97950539A patent/EP0946510B1/en not_active Expired - Lifetime
- 1997-12-09 SK SK763-99A patent/SK283300B6/sk unknown
- 1997-12-09 ID IDW990536A patent/ID21662A/id unknown
- 1997-12-09 NZ NZ336028A patent/NZ336028A/en unknown
- 1997-12-09 CN CNB971808376A patent/CN1154635C/zh not_active Expired - Fee Related
- 1997-12-09 AT AT97950539T patent/ATE266638T1/de not_active IP Right Cessation
- 1997-12-09 US US09/029,468 patent/US6153626A/en not_active Expired - Lifetime
- 1997-12-09 CA CA002274117A patent/CA2274117A1/en not_active Abandoned
- 1997-12-09 AU AU53513/98A patent/AU738002B2/en not_active Ceased
- 1997-12-09 IL IL13053697A patent/IL130536A0/xx unknown
- 1997-12-09 WO PCT/SE1997/002051 patent/WO1998028270A1/en not_active Ceased
- 1997-12-09 ES ES97950539T patent/ES2219783T3/es not_active Expired - Lifetime
- 1997-12-09 CZ CZ992200A patent/CZ220099A3/cs unknown
- 1997-12-09 ZA ZA9711049A patent/ZA9711049B/xx unknown
- 1997-12-09 CN CNA2004100324204A patent/CN1539824A/zh active Pending
- 1997-12-09 DE DE69729115T patent/DE69729115T2/de not_active Expired - Fee Related
- 1997-12-09 DK DK97950539T patent/DK0946510T3/da active
- 1997-12-09 PL PL97334370A patent/PL188945B1/pl not_active IP Right Cessation
- 1997-12-09 JP JP52867098A patent/JP2001507021A/ja not_active Ceased
- 1997-12-09 HU HU0000613A patent/HUP0000613A3/hu unknown
- 1997-12-09 PT PT97950539T patent/PT946510E/pt unknown
- 1997-12-09 RU RU99115746/04A patent/RU2193030C2/ru not_active IP Right Cessation
- 1997-12-09 KR KR1019997005586A patent/KR20000069600A/ko not_active Ceased
- 1997-12-09 TR TR1999/01411T patent/TR199901411T2/xx unknown
- 1997-12-09 EP EP04002901A patent/EP1428821A1/en not_active Withdrawn
- 1997-12-19 MY MYPI97006174A patent/MY132705A/en unknown
- 1997-12-19 AR ARP970106076A patent/AR010378A1/es active IP Right Grant
-
1999
- 1999-06-11 IS IS5078A patent/IS5078A/is unknown
- 1999-06-18 NO NO19993023A patent/NO313632B1/no unknown
-
2000
- 2000-08-25 US US09/645,565 patent/US6399635B1/en not_active Expired - Fee Related
-
2002
- 2002-04-15 US US10/121,683 patent/US6710179B2/en not_active Expired - Fee Related
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