NO328848B1 - Variolinderivater og deres anvendelse som antitumormidler - Google Patents
Variolinderivater og deres anvendelse som antitumormidler Download PDFInfo
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- NO328848B1 NO328848B1 NO20040113A NO20040113A NO328848B1 NO 328848 B1 NO328848 B1 NO 328848B1 NO 20040113 A NO20040113 A NO 20040113A NO 20040113 A NO20040113 A NO 20040113A NO 328848 B1 NO328848 B1 NO 328848B1
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- Prior art keywords
- compound
- mmol
- solution
- hydrogen
- nmr
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- 229930186114 Variolin Natural products 0.000 title claims abstract description 14
- 239000002246 antineoplastic agent Substances 0.000 title description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 62
- 150000002367 halogens Chemical class 0.000 claims abstract description 27
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 26
- 125000001424 substituent group Chemical group 0.000 claims abstract description 24
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 17
- 125000003118 aryl group Chemical group 0.000 claims abstract description 15
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 15
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 15
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 14
- 125000006710 (C2-C12) alkenyl group Chemical group 0.000 claims abstract description 12
- 125000006711 (C2-C12) alkynyl group Chemical group 0.000 claims abstract description 12
- 125000004181 carboxyalkyl group Chemical group 0.000 claims abstract description 10
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 5
- 150000001875 compounds Chemical class 0.000 claims description 114
- 239000000460 chlorine Substances 0.000 claims description 104
- 239000001257 hydrogen Substances 0.000 claims description 35
- 238000000034 method Methods 0.000 claims description 26
- -1 CO2CH3 Chemical group 0.000 claims description 21
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- 125000004414 alkyl thio group Chemical group 0.000 claims description 10
- 229940079593 drug Drugs 0.000 claims description 10
- 206010028980 Neoplasm Diseases 0.000 claims description 9
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 9
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims description 7
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 7
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 7
- 201000011510 cancer Diseases 0.000 claims description 7
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
- 125000004104 aryloxy group Chemical group 0.000 claims description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 125000005842 heteroatom Chemical group 0.000 claims description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 3
- 125000004434 sulfur atom Chemical group 0.000 claims description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 2
- 230000008569 process Effects 0.000 claims description 2
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- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 7
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 1
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims 1
- 125000002837 carbocyclic group Chemical group 0.000 abstract 1
- 125000000623 heterocyclic group Chemical group 0.000 abstract 1
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- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 162
- 239000000243 solution Substances 0.000 description 160
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 52
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 48
- 239000000203 mixture Substances 0.000 description 48
- 235000017557 sodium bicarbonate Nutrition 0.000 description 45
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 45
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- 239000011734 sodium Substances 0.000 description 19
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 18
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- 101150041968 CDC13 gene Proteins 0.000 description 14
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- SECBGKYJKCNDID-UHFFFAOYSA-N 4-iodo-2-methylsulfanylpyrimidine Chemical compound CSC1=NC=CC(I)=N1 SECBGKYJKCNDID-UHFFFAOYSA-N 0.000 description 13
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 13
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- 230000012010 growth Effects 0.000 description 9
- 238000000746 purification Methods 0.000 description 9
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 8
- 230000000259 anti-tumor effect Effects 0.000 description 8
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 8
- JTQQDEMYPLKSDW-UHFFFAOYSA-N 5-(2-aminopyrimidin-4-yl)pyrido[2,3]pyrrolo[4,5-c]pyrimidin-9-amine Chemical compound NC1=NC=CC(C2=C3C=CN=C(N)N3C3=NC=CC=C32)=N1 JTQQDEMYPLKSDW-UHFFFAOYSA-N 0.000 description 7
- QUKHTBITMVKWCA-UHFFFAOYSA-N methyl 9-amino-4-oxo-1h-pyrido[2,3]pyrrolo[4,5-c]pyrimidine-5-carboxylate Chemical compound N1C=CC(=O)C2=C1N1C(N)=NC=CC1=C2C(=O)OC QUKHTBITMVKWCA-UHFFFAOYSA-N 0.000 description 7
- IDPURXSQCKYKIJ-UHFFFAOYSA-N 1-(4-methoxyphenyl)methanamine Chemical compound COC1=CC=C(CN)C=C1 IDPURXSQCKYKIJ-UHFFFAOYSA-N 0.000 description 6
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- RXTRRIFWCJEMEL-UHFFFAOYSA-N 2-chloropyridine-3-carbonyl chloride Chemical compound ClC(=O)C1=CC=CN=C1Cl RXTRRIFWCJEMEL-UHFFFAOYSA-N 0.000 description 4
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 4
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
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Classifications
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- 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
- C07D213/60—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 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
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/64—One oxygen atom attached in position 2 or 6
-
- 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
- C07D213/60—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 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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
- C07D239/28—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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/38—One sulfur atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/06—Peri-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
- C07D471/14—Ortho-condensed systems
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Steroid Compounds (AREA)
- Saccharide Compounds (AREA)
- Carbon And Carbon Compounds (AREA)
- Transition And Organic Metals Composition Catalysts For Addition Polymerization (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0116966.3A GB0116966D0 (en) | 2001-07-11 | 2001-07-11 | Anittumoral compounds |
| PCT/GB2002/003197 WO2003006457A1 (en) | 2001-07-11 | 2002-07-11 | Variolin derivatives and their use as antitumor agents |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NO20040113L NO20040113L (no) | 2004-03-09 |
| NO328848B1 true NO328848B1 (no) | 2010-05-31 |
Family
ID=9918335
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20040113A NO328848B1 (no) | 2001-07-11 | 2004-01-12 | Variolinderivater og deres anvendelse som antitumormidler |
Country Status (20)
| Country | Link |
|---|---|
| US (2) | US7495000B2 (ru) |
| EP (2) | EP1404668B1 (ru) |
| JP (1) | JP4369225B2 (ru) |
| KR (1) | KR100929616B1 (ru) |
| CN (1) | CN1553906B (ru) |
| AT (2) | ATE396987T1 (ru) |
| AU (1) | AU2002317329B2 (ru) |
| CA (1) | CA2453418C (ru) |
| DE (2) | DE60226869D1 (ru) |
| ES (2) | ES2354991T3 (ru) |
| GB (1) | GB0116966D0 (ru) |
| HK (1) | HK1060354A1 (ru) |
| HU (1) | HUP0402658A2 (ru) |
| IL (2) | IL159792A0 (ru) |
| MX (1) | MXPA04000355A (ru) |
| NO (1) | NO328848B1 (ru) |
| NZ (1) | NZ530556A (ru) |
| PL (1) | PL366894A1 (ru) |
| RU (1) | RU2302419C2 (ru) |
| WO (1) | WO2003006457A1 (ru) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK1299388T3 (da) | 2000-07-11 | 2009-08-31 | Pharma Mar Sa | Variolin-derivater som anti-cancermidler |
| GB0019117D0 (en) | 2000-08-03 | 2000-09-27 | Univ Barcelona | Derivatives of variolin B |
| GB0116966D0 (en) | 2001-07-11 | 2001-09-05 | Pharma Mar Sa | Anittumoral compounds |
| DK2300475T3 (en) * | 2008-06-11 | 2014-12-08 | Genentech Inc | Diazacarbazoler and methods of using |
| JOP20190254A1 (ar) | 2017-04-27 | 2019-10-27 | Pharma Mar Sa | مركبات مضادة للأورام |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK1299388T3 (da) * | 2000-07-11 | 2009-08-31 | Pharma Mar Sa | Variolin-derivater som anti-cancermidler |
| GB0019117D0 (en) * | 2000-08-03 | 2000-09-27 | Univ Barcelona | Derivatives of variolin B |
| GB0116966D0 (en) | 2001-07-11 | 2001-09-05 | Pharma Mar Sa | Anittumoral compounds |
-
2001
- 2001-07-11 GB GBGB0116966.3A patent/GB0116966D0/en not_active Ceased
-
2002
- 2002-07-11 EP EP02745614A patent/EP1404668B1/en not_active Expired - Lifetime
- 2002-07-11 US US10/483,525 patent/US7495000B2/en not_active Expired - Fee Related
- 2002-07-11 NZ NZ530556A patent/NZ530556A/en not_active IP Right Cessation
- 2002-07-11 EP EP07013582A patent/EP1867645B1/en not_active Expired - Lifetime
- 2002-07-11 AU AU2002317329A patent/AU2002317329B2/en not_active Ceased
- 2002-07-11 JP JP2003512229A patent/JP4369225B2/ja not_active Expired - Fee Related
- 2002-07-11 MX MXPA04000355A patent/MXPA04000355A/es active IP Right Grant
- 2002-07-11 DE DE60226869T patent/DE60226869D1/de not_active Expired - Lifetime
- 2002-07-11 AT AT02745614T patent/ATE396987T1/de not_active IP Right Cessation
- 2002-07-11 AT AT07013582T patent/ATE480533T1/de not_active IP Right Cessation
- 2002-07-11 ES ES07013582T patent/ES2354991T3/es not_active Expired - Lifetime
- 2002-07-11 CN CN028175298A patent/CN1553906B/zh not_active Expired - Fee Related
- 2002-07-11 RU RU2004103857/04A patent/RU2302419C2/ru not_active IP Right Cessation
- 2002-07-11 KR KR1020047000500A patent/KR100929616B1/ko not_active IP Right Cessation
- 2002-07-11 CA CA2453418A patent/CA2453418C/en not_active Expired - Fee Related
- 2002-07-11 PL PL02366894A patent/PL366894A1/xx not_active Application Discontinuation
- 2002-07-11 ES ES02745614T patent/ES2307768T3/es not_active Expired - Lifetime
- 2002-07-11 HU HU0402658A patent/HUP0402658A2/hu unknown
- 2002-07-11 WO PCT/GB2002/003197 patent/WO2003006457A1/en active IP Right Grant
- 2002-07-11 IL IL15979202A patent/IL159792A0/xx unknown
- 2002-07-11 DE DE60237652T patent/DE60237652D1/de not_active Expired - Lifetime
-
2004
- 2004-01-11 IL IL159792A patent/IL159792A/en not_active IP Right Cessation
- 2004-01-12 NO NO20040113A patent/NO328848B1/no not_active IP Right Cessation
- 2004-05-07 HK HK04103219A patent/HK1060354A1/xx not_active IP Right Cessation
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2009
- 2009-01-07 US US12/349,813 patent/US7772241B2/en not_active Expired - Fee Related
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| MM1K | Lapsed by not paying the annual fees |