JP4307719B2 - 新形成治療用のｎ−ベンジル−３−インデニルアセトアミド誘導体 - Google Patents
新形成治療用のｎ−ベンジル−３−インデニルアセトアミド誘導体 Download PDFInfo
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- JP4307719B2 JP4307719B2 JP2000538992A JP2000538992A JP4307719B2 JP 4307719 B2 JP4307719 B2 JP 4307719B2 JP 2000538992 A JP2000538992 A JP 2000538992A JP 2000538992 A JP2000538992 A JP 2000538992A JP 4307719 B2 JP4307719 B2 JP 4307719B2
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- Prior art keywords
- lower alkyl
- group
- amino
- hydroxy
- alkylamino
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- 238000011282 treatment Methods 0.000 title abstract description 19
- NNPSGLWEKFBPKR-UHFFFAOYSA-N n-benzyl-2-(3h-inden-1-yl)acetamide Chemical class C=1CC2=CC=CC=C2C=1CC(=O)NCC1=CC=CC=C1 NNPSGLWEKFBPKR-UHFFFAOYSA-N 0.000 title abstract 2
- 230000001613 neoplastic effect Effects 0.000 title description 8
- -1 heterocyclic aldehydes Chemical class 0.000 claims abstract description 105
- 150000001875 compounds Chemical class 0.000 claims description 162
- 125000000217 alkyl group Chemical group 0.000 claims description 88
- 229910052739 hydrogen Inorganic materials 0.000 claims description 71
- 125000003282 alkyl amino group Chemical group 0.000 claims description 61
- 239000001257 hydrogen Substances 0.000 claims description 42
- 150000002431 hydrogen Chemical class 0.000 claims description 33
- 125000003545 alkoxy group Chemical group 0.000 claims description 27
- 229910052736 halogen Inorganic materials 0.000 claims description 27
- 150000002367 halogens Chemical class 0.000 claims description 27
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 27
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 22
- 125000001424 substituent group Chemical group 0.000 claims description 20
- 239000008194 pharmaceutical composition Substances 0.000 claims description 18
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- 125000004076 pyridyl group Chemical group 0.000 claims description 8
- 239000003937 drug carrier Substances 0.000 claims description 7
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 6
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 6
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 6
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 6
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 5
- 125000004414 alkyl thio group Chemical group 0.000 claims description 5
- ZOOODBUHSVUZEM-UHFFFAOYSA-N ethoxymethanedithioic acid Chemical compound CCOC(S)=S ZOOODBUHSVUZEM-UHFFFAOYSA-N 0.000 claims description 5
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- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 3
- YDVJBLJCSLVMSY-UHFFFAOYSA-N carbamoyl cyanide Chemical compound NC(=O)C#N YDVJBLJCSLVMSY-UHFFFAOYSA-N 0.000 claims description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 3
- 125000002541 furyl group Chemical group 0.000 claims description 3
- 125000002883 imidazolyl group Chemical group 0.000 claims description 3
- 125000001041 indolyl group Chemical group 0.000 claims description 3
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- 125000003226 pyrazolyl group Chemical group 0.000 claims description 3
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 3
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- 125000001544 thienyl group Chemical group 0.000 claims description 3
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- 238000000034 method Methods 0.000 description 71
- 238000006243 chemical reaction Methods 0.000 description 45
- 238000001953 recrystallisation Methods 0.000 description 37
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 36
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- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 21
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- 239000000047 product Substances 0.000 description 13
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- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
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- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 10
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 10
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- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Chemical compound C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 8
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 8
- 150000001299 aldehydes Chemical class 0.000 description 8
- 239000012267 brine Substances 0.000 description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 8
- 239000000284 extract Substances 0.000 description 8
- 229910052731 fluorine Inorganic materials 0.000 description 8
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical group O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 8
- 230000002401 inhibitory effect Effects 0.000 description 8
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- 239000012044 organic layer Substances 0.000 description 8
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 8
- NHCGQXPQGHFCPN-UHFFFAOYSA-N amino methanesulfonate Chemical compound CS(=O)(=O)ON NHCGQXPQGHFCPN-UHFFFAOYSA-N 0.000 description 7
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- 238000003756 stirring Methods 0.000 description 7
- ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 6
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- 229910052943 magnesium sulfate Inorganic materials 0.000 description 6
- 235000019341 magnesium sulphate Nutrition 0.000 description 6
- BGUWFUQJCDRPTL-UHFFFAOYSA-N pyridine-4-carbaldehyde Chemical compound O=CC1=CC=NC=C1 BGUWFUQJCDRPTL-UHFFFAOYSA-N 0.000 description 6
- MGCGJBXTNWUHQE-UHFFFAOYSA-N quinoline-4-carbaldehyde Chemical group C1=CC=C2C(C=O)=CC=NC2=C1 MGCGJBXTNWUHQE-UHFFFAOYSA-N 0.000 description 6
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- MBVFRSJFKMJRHA-UHFFFAOYSA-N 4-fluoro-1-benzofuran-7-carbaldehyde Chemical compound FC1=CC=C(C=O)C2=C1C=CO2 MBVFRSJFKMJRHA-UHFFFAOYSA-N 0.000 description 4
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/26—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/56—Amides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/12—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D215/14—Radicals substituted by 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
- C07D237/02—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
- C07D237/08—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 only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/12—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyridine Compounds (AREA)
- Indole Compounds (AREA)
- Quinoline Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Hydrogenated Pyridines (AREA)
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Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/989,353 US5948779A (en) | 1997-12-12 | 1997-12-12 | Substituted condensation products of n-benzyl-3-indenyl acetamides with heterocyclic aldehydes |
| US08/989,353 | 1997-12-12 | ||
| US09/206,245 | 1998-12-07 | ||
| US09/206,245 US6066634A (en) | 1997-12-12 | 1998-12-07 | Substituted condensation products of N-benzyl-3-indenylacetamides heterocyclic aldehydes for neoplasia |
| PCT/GB1998/003712 WO1999031065A1 (en) | 1997-12-12 | 1998-12-11 | N-benzyl-3-indenylacetamides derivatives for treating neoplasia |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2002508358A JP2002508358A (ja) | 2002-03-19 |
| JP2002508358A5 JP2002508358A5 (enExample) | 2006-02-16 |
| JP4307719B2 true JP4307719B2 (ja) | 2009-08-05 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2000538992A Expired - Fee Related JP4307719B2 (ja) | 1997-12-12 | 1998-12-11 | 新形成治療用のｎ−ベンジル−３−インデニルアセトアミド誘導体 |
Country Status (18)
| Country | Link |
|---|---|
| US (3) | US6166053A (enExample) |
| EP (1) | EP1044187B1 (enExample) |
| JP (1) | JP4307719B2 (enExample) |
| CN (1) | CN100436418C (enExample) |
| AT (1) | ATE257152T1 (enExample) |
| AU (1) | AU752072B2 (enExample) |
| BR (1) | BR9813540A (enExample) |
| CA (1) | CA2314339C (enExample) |
| CZ (1) | CZ298826B6 (enExample) |
| DE (1) | DE69820908T2 (enExample) |
| ES (1) | ES2212383T3 (enExample) |
| HU (1) | HU227153B1 (enExample) |
| IL (1) | IL136603A0 (enExample) |
| NO (1) | NO317097B1 (enExample) |
| NZ (1) | NZ504958A (enExample) |
| PL (1) | PL196936B1 (enExample) |
| TR (1) | TR200001687T2 (enExample) |
| WO (1) | WO1999031065A1 (enExample) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2314339C (en) * | 1997-12-12 | 2009-09-08 | Cell Pathways, Inc. | N-benzyl-3-indenylacetamide derivatives for treating neoplasia |
| IL132366A0 (en) * | 1998-10-15 | 2001-03-19 | Cell Pathways Inc | Methods for identifying compounds for inhibition of neoplastic lesions and pharmaceutical compositions containing such compounds |
| AU2001255849B8 (en) * | 2000-04-19 | 2006-04-27 | Lilly Icos, Llc. | PDE-V inhibitors for treatment of Parkinson's Disease |
| DE10058663A1 (de) * | 2000-11-25 | 2002-05-29 | Merck Patent Gmbh | Verwendung von Thienopyrimidinen |
| WO2002067936A1 (en) * | 2001-02-21 | 2002-09-06 | Cell Pathways, Inc. | Methods for treatment of inflammatory bowel disease |
| DE10135815A1 (de) * | 2001-07-23 | 2003-02-06 | Bayer Ag | Verwendung von 2-Alkoxyphenyl-substituierten Imidazotriazinonen |
| US20030073740A1 (en) * | 2001-08-23 | 2003-04-17 | Whitehead Clark M. | Methods for treatment of lupus erythematosus |
| US6479493B1 (en) * | 2001-08-23 | 2002-11-12 | Cell Pathways, Inc. | Methods for treatment of type I diabetes |
| US20030073711A1 (en) * | 2001-08-23 | 2003-04-17 | Whitehead Clark M. | Methods for treatment of scleroderma |
| CN100398522C (zh) * | 2003-08-20 | 2008-07-02 | Irm责任有限公司 | 组织蛋白酶s的抑制剂 |
| US6995622B2 (en) * | 2004-01-09 | 2006-02-07 | Robert Bosh Gmbh | Frequency and/or phase compensated microelectromechanical oscillator |
| CA2568906C (en) | 2004-06-02 | 2010-09-21 | Merit Diamond Corporation | Comfort interior for jewelry and jewelry including that interior |
| CN1332930C (zh) * | 2005-08-05 | 2007-08-22 | 中国科学院上海有机化学研究所 | 制备乙氰菊酯前体的方法 |
| CA2635093C (en) * | 2006-01-04 | 2012-06-26 | Southern Research Institute | Derivatives of sulindac, use thereof and preparation thereof |
| WO2009022756A1 (ja) * | 2007-08-13 | 2009-02-19 | Katayama Chemical Industries Co., Ltd. | 虚血性疾患の診断及び治療 |
| EP2365746B1 (en) * | 2008-11-04 | 2014-07-16 | Wellstat Therapeutics Corporation | Synthesis of (phenylalkyloxy)phenyl-oxobutanoic acids |
| CN109703393A (zh) | 2009-08-07 | 2019-05-03 | 奥克兰联合服务有限公司 | 感应电力传递装置 |
| US20160168108A1 (en) | 2014-12-16 | 2016-06-16 | Adt Pharmaceuticals, Inc. | Method of treating or preventing ras-mediated diseases |
| US9862698B2 (en) | 2014-12-16 | 2018-01-09 | Adt Pharmaceuticals, Inc. | Indenyl compounds, pharmaceutical compositions, and medical uses thereof |
| CN112020354A (zh) | 2018-04-26 | 2020-12-01 | Adt制药有限责任公司 | 抗癌茚类、茚满类、氮杂茚类、氮杂茚满类、药物组合物和用途 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU650720B2 (en) * | 1991-03-08 | 1994-06-30 | Fgn, Inc. | Method for treating patients with precancerous lesions by administering substituted sulfonyl indenyl acetic and propionic acids and esters thereof |
| US6063818A (en) * | 1996-06-13 | 2000-05-16 | Cell Pathways Inc. | Substituted benzylidene indenyl formamides, acetamides and propionamides |
| US5948779A (en) * | 1997-12-12 | 1999-09-07 | Cell Pathways, Inc. | Substituted condensation products of n-benzyl-3-indenyl acetamides with heterocyclic aldehydes |
| CA2314339C (en) * | 1997-12-12 | 2009-09-08 | Cell Pathways, Inc. | N-benzyl-3-indenylacetamide derivatives for treating neoplasia |
-
1998
- 1998-12-11 CA CA002314339A patent/CA2314339C/en not_active Expired - Fee Related
- 1998-12-11 PL PL341151A patent/PL196936B1/pl not_active IP Right Cessation
- 1998-12-11 AT AT98959050T patent/ATE257152T1/de not_active IP Right Cessation
- 1998-12-11 WO PCT/GB1998/003712 patent/WO1999031065A1/en not_active Ceased
- 1998-12-11 JP JP2000538992A patent/JP4307719B2/ja not_active Expired - Fee Related
- 1998-12-11 IL IL13660398A patent/IL136603A0/xx active IP Right Grant
- 1998-12-11 DE DE69820908T patent/DE69820908T2/de not_active Expired - Lifetime
- 1998-12-11 ES ES98959050T patent/ES2212383T3/es not_active Expired - Lifetime
- 1998-12-11 EP EP98959050A patent/EP1044187B1/en not_active Expired - Lifetime
- 1998-12-11 CN CNB988118955A patent/CN100436418C/zh not_active Expired - Fee Related
- 1998-12-11 AU AU14981/99A patent/AU752072B2/en not_active Ceased
- 1998-12-11 NZ NZ504958A patent/NZ504958A/xx unknown
- 1998-12-11 CZ CZ20002157A patent/CZ298826B6/cs not_active IP Right Cessation
- 1998-12-11 TR TR2000/01687T patent/TR200001687T2/xx unknown
- 1998-12-11 BR BR9813540-6A patent/BR9813540A/pt not_active Application Discontinuation
- 1998-12-11 HU HU0100170A patent/HU227153B1/hu not_active IP Right Cessation
-
2000
- 2000-01-24 US US09/490,269 patent/US6166053A/en not_active Expired - Lifetime
- 2000-06-09 NO NO20002972A patent/NO317097B1/no not_active IP Right Cessation
- 2000-12-20 US US09/741,970 patent/US6426349B1/en not_active Expired - Fee Related
-
2002
- 2002-07-26 US US10/206,687 patent/US6610854B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| NZ504958A (en) | 2003-03-28 |
| PL341151A1 (en) | 2001-03-26 |
| PL196936B1 (pl) | 2008-02-29 |
| NO20002972L (no) | 2000-08-09 |
| CA2314339A1 (en) | 1999-06-24 |
| US6426349B1 (en) | 2002-07-30 |
| EP1044187A1 (en) | 2000-10-18 |
| HUP0100170A3 (en) | 2001-12-28 |
| TR200001687T2 (tr) | 2000-10-23 |
| DE69820908T2 (de) | 2004-12-23 |
| ATE257152T1 (de) | 2004-01-15 |
| AU1498199A (en) | 1999-07-05 |
| AU752072B2 (en) | 2002-09-05 |
| NO20002972D0 (no) | 2000-06-09 |
| NO317097B1 (no) | 2004-08-09 |
| HUP0100170A1 (hu) | 2001-07-30 |
| DE69820908D1 (de) | 2004-02-05 |
| CZ298826B6 (cs) | 2008-02-20 |
| WO1999031065A1 (en) | 1999-06-24 |
| CA2314339C (en) | 2009-09-08 |
| BR9813540A (pt) | 2000-10-10 |
| ES2212383T3 (es) | 2004-07-16 |
| EP1044187B1 (en) | 2004-01-02 |
| IL136603A0 (en) | 2001-06-14 |
| HU227153B1 (en) | 2010-08-30 |
| CZ20002157A3 (cs) | 2000-10-11 |
| JP2002508358A (ja) | 2002-03-19 |
| US20030009033A1 (en) | 2003-01-09 |
| US6166053A (en) | 2000-12-26 |
| US6610854B2 (en) | 2003-08-26 |
| CN100436418C (zh) | 2008-11-26 |
| CN1281436A (zh) | 2001-01-24 |
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