RU2006122853A - Производные диарилмочевины для лечения заболеваний, зависимых от протеинкиназы - Google Patents
Производные диарилмочевины для лечения заболеваний, зависимых от протеинкиназы Download PDFInfo
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- RU2006122853A RU2006122853A RU2006122853/04A RU2006122853A RU2006122853A RU 2006122853 A RU2006122853 A RU 2006122853A RU 2006122853/04 A RU2006122853/04 A RU 2006122853/04A RU 2006122853 A RU2006122853 A RU 2006122853A RU 2006122853 A RU2006122853 A RU 2006122853A
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- 201000010099 disease Diseases 0.000 title claims 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims 13
- 102000001253 Protein Kinase Human genes 0.000 title claims 7
- 108060006633 protein kinase Proteins 0.000 title claims 7
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical class NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 title 1
- 230000001419 dependent effect Effects 0.000 claims 13
- 150000001875 compounds Chemical class 0.000 claims 8
- 150000003839 salts Chemical class 0.000 claims 7
- OBHVFBJZHBSDOF-UHFFFAOYSA-N 1-phenyl-3-(4-pyrimidin-4-yloxyphenyl)urea Chemical compound C=1C=C(OC=2N=CN=CC=2)C=CC=1NC(=O)NC1=CC=CC=C1 OBHVFBJZHBSDOF-UHFFFAOYSA-N 0.000 claims 5
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims 5
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims 5
- 229910052757 nitrogen Inorganic materials 0.000 claims 5
- 101100335081 Mus musculus Flt3 gene Proteins 0.000 claims 4
- 239000001257 hydrogen Substances 0.000 claims 4
- 229910052739 hydrogen Inorganic materials 0.000 claims 4
- 206010028980 Neoplasm Diseases 0.000 claims 3
- 239000012634 fragment Substances 0.000 claims 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 3
- 229910052760 oxygen Inorganic materials 0.000 claims 3
- 239000008194 pharmaceutical composition Substances 0.000 claims 3
- WEVYNIUIFUYDGI-UHFFFAOYSA-N 3-[6-[4-(trifluoromethoxy)anilino]-4-pyrimidinyl]benzamide Chemical compound NC(=O)C1=CC=CC(C=2N=CN=C(NC=3C=CC(OC(F)(F)F)=CC=3)C=2)=C1 WEVYNIUIFUYDGI-UHFFFAOYSA-N 0.000 claims 2
- 208000024770 Thyroid neoplasm Diseases 0.000 claims 2
- 230000002062 proliferating effect Effects 0.000 claims 2
- 239000000126 substance Substances 0.000 claims 2
- 229910052717 sulfur Inorganic materials 0.000 claims 2
- 201000002510 thyroid cancer Diseases 0.000 claims 2
- 206010006187 Breast cancer Diseases 0.000 claims 1
- 208000026310 Breast neoplasm Diseases 0.000 claims 1
- 206010009944 Colon cancer Diseases 0.000 claims 1
- 101000579425 Homo sapiens Proto-oncogene tyrosine-protein kinase receptor Ret Proteins 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims 1
- 229940100514 Syk tyrosine kinase inhibitor Drugs 0.000 claims 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 claims 1
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 claims 1
- LUBJCRLGQSPQNN-UHFFFAOYSA-N Z-phenylurea Natural products NC(=O)NC1=CC=CC=C1 LUBJCRLGQSPQNN-UHFFFAOYSA-N 0.000 claims 1
- 125000000217 alkyl group Chemical group 0.000 claims 1
- 125000002947 alkylene group Chemical group 0.000 claims 1
- 125000005530 alkylenedioxy group Chemical group 0.000 claims 1
- 125000004429 atom Chemical group 0.000 claims 1
- 201000011510 cancer Diseases 0.000 claims 1
- 208000029742 colonic neoplasm Diseases 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 230000005764 inhibitory process Effects 0.000 claims 1
- 201000005202 lung cancer Diseases 0.000 claims 1
- 208000020816 lung neoplasm Diseases 0.000 claims 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 1
- 125000004430 oxygen atom Chemical group O* 0.000 claims 1
- 201000002528 pancreatic cancer Diseases 0.000 claims 1
- 208000008443 pancreatic carcinoma Diseases 0.000 claims 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- -1 pyrimidin-4-yloxy Chemical group 0.000 claims 1
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
- C07D211/68—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 one double bond between ring members or between a ring member and a non-ring member
- C07D211/72—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 one double bond between ring members or between a ring member and a non-ring member 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
- C07D211/78—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C04—CEMENTS; CONCRETE; ARTIFICIAL STONE; CERAMICS; REFRACTORIES
- C04B—LIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
- C04B35/00—Shaped ceramic products characterised by their composition; Ceramics compositions; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products
- C04B35/622—Forming processes; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products
- C04B35/626—Preparing or treating the powders individually or as batches ; preparing or treating macroscopic reinforcing agents for ceramic products, e.g. fibres; mechanical aspects section B
- C04B35/63—Preparing or treating the powders individually or as batches ; preparing or treating macroscopic reinforcing agents for ceramic products, e.g. fibres; mechanical aspects section B using additives specially adapted for forming the products, e.g.. binder binders
- C04B35/632—Organic additives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
-
- 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
- C07D239/34—One oxygen atom
-
- 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
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/47—One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
-
- 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
- C07D401/12—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 chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Health & Medical Sciences (AREA)
- Ceramic Engineering (AREA)
- Manufacturing & Machinery (AREA)
- Inorganic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Structural Engineering (AREA)
- Materials Engineering (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Claims (12)
1. Применение соединения формулы I
где G означает отсутствующий радикал, (низш.)алкилен или С3-С5циклоалкилен, a Z означает радикал формулы Ia
или G означает отсутствующий радикал, а Z означает радикал формулы Ib
А означает СН, N или N→O, а А' означает N или N→O, при условии, что не более чем один из А и А' может означать N→O,
n равно 1 или 2,
m равно 0, 1 или 2,
р равно 0, 2 или 3,
r равно 0-5,
Х означает NR, если р равно 0, где R означает водород или органическую фрагмент, или, если р равно 2 или 3, Х означает азот, который вместе с группой (СН2)р и химическими связями, указанными пунктирными (прерывистыми) линиями (включая атомы, к которым они присоединены), образуют цикл, или
Х означает СНК, где К означает (низш.)алкил или водород, а р равно нулю, при условии, что химические связи, указанные пунктирными линиями отсутствуют, если р равно нулю,
Y1 означает О, S или СН2,
Y2 означает О, S или NH,
при условии, что (Y1)n-(Y2)m не включает группы O-O, S-S, NH-O, NH-S или S-O,
каждый R1, R2, R3 и R5 независимо друг от друга означает водород, или неорганический или органический фрагмент или любые два из них образуют мостиковую группу (низш.)алкилендиокси, связанную через атомы кислорода, а оставшийся один из этих фрагментов означает водород или неорганический или органический фрагмент,
и R4 (присутствующий, если r не равно нулю) означает неорганический или органический фрагмент,
или его таутомера или фармацевтически приемлемой соли для получения фармацевтической композиции, предназначенной для лечения RET-зависимых заболеваний.
2. Применение по п.1, где RET-зависимое заболевание означает RET-зависимое опухолевое заболевание.
3. Применение по п.2, где RET-зависимое опухолевое заболевание выбирают из рака толстой кишки, рака легких, рака молочной железы, рака поджелудочной железы и рака щитовидной железы.
4. Применение по п.3, где рак означает рак щитовидной железы.
5. Производное N-[4-(пиримидин-4-илокси)фенил]-N'-фенилмочевины, выбранное из группы, включающей соединения, описанные в примерах 1-67, 68-70 или 71-95, или его соль.
6. Фармацевтическая композиция, включающая производное N-[4-(пиримидин-4-илокси)фенил]-N'-фенилмочевины, выбранное из группы, включающей соединения, описанные в примерах 1-67, 68-70 или 71-95, или его фармацевтически приемлемую соль, и фармацевтически приемлемый носитель.
7. Производное N-[4-(пиримидин-4-илокси)фенил]-N'-фенилмочевины, выбранное из группы, включающей соединения, описанные в примерах 1-67, 68-70 или 71-95, или его фармацевтически приемлемая соль, для применения при лечении животного или человека, особенно для лечения зависимого от протеинкиназы заболевания.
8. Соединение по п.7, где зависимое от протеинкиназы заболевание, подлежащее лечению, означает заболевание, зависимое от протеинтирозинкиназы, особенно пролиферативное заболевание, зависимое от любой одной или более следующих протеинтирозинкиназ: с-Abl, Bcr-Abl, Flt-3, RET, VEGF-R и/или Tek, особенно Flt-3.
9. Применение производного N-[4-(пиримидин-4-илокси)фенил]-N'-фенилмочевины, выбранного из группы, включающей соединения, описанные в примерах 1-67, 68-70 или 71-95, или его фармацевтически приемлемой соли, для использования при лечении зависимого от протеинкиназы заболевания.
10. Применение производного N-[4-(пиримидин-4-илокси)фенил]-N'-фенилмочевины, выбранного из группы, включающей соединения, описанные в примерах 1-67, 68-70 или 71-95, или его фармацевтически приемлемой соли, для приготовления фармацевтической композиции, предназначенной для использования при лечении зависимого от протеинкиназы заболевания.
11. Применение по п.9 или 10, где зависимое от протеинкиназы заболевание означает заболевание, зависимое от протеинтирозинкиназы, особенно пролиферативное заболевание, зависимое от любой одной или более следующих протеинтирозинкиназ: с-Abl, Bcr-Abl, Flt-3, RET, VEGF-R и/или Tek, особенно Flt-3.
12. Способ лечения заболевания, чувствительного к ингибированию протеинкиназы (особенно тирозинпротеинкиназы), включающий введение теплокровному животному, например человеку, которому необходимо такое лечение, профилактически или предпочтительно терапевтически эффективного количества производного N-[4-(пиримидин-4-илокси)фенил]-N'-фенилмочевины, выбранного из группы, включающей соединения, описанные в примерах 1-67, 68-70 или 71-95, или его фармацевтически приемлемой соли.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0327734.0 | 2003-11-28 | ||
| GB0327734A GB0327734D0 (en) | 2003-11-28 | 2003-11-28 | Organic compounds |
| GB0417805.9 | 2004-08-10 | ||
| GB0417805A GB0417805D0 (en) | 2004-08-10 | 2004-08-10 | Organic compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| RU2006122853A true RU2006122853A (ru) | 2008-01-10 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2006122853/04A RU2006122853A (ru) | 2003-11-28 | 2004-11-26 | Производные диарилмочевины для лечения заболеваний, зависимых от протеинкиназы |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US20080312192A1 (ru) |
| EP (1) | EP1689376A2 (ru) |
| JP (1) | JP2007515400A (ru) |
| KR (1) | KR20060110307A (ru) |
| AR (1) | AR047496A1 (ru) |
| AU (2) | AU2004292773A1 (ru) |
| BR (1) | BRPI0416935A (ru) |
| CA (1) | CA2546673A1 (ru) |
| PE (1) | PE20051046A1 (ru) |
| RU (1) | RU2006122853A (ru) |
| TW (1) | TW200529849A (ru) |
| WO (1) | WO2005051366A2 (ru) |
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| EP1604665B1 (en) | 2003-03-10 | 2011-05-11 | Eisai R&D Management Co., Ltd. | C-kit kinase inhibitor |
| AU2004265288A1 (en) | 2003-07-30 | 2005-02-24 | Rigel Pharmaceuticals, Inc. | 2,4-pyrimidinediamine compounds for use in the treatment or prevention of autoimmune diseases |
| EP1683785B1 (en) | 2003-11-11 | 2013-10-16 | Eisai R&D Management Co., Ltd. | Urea derivative and process for producing the same |
| AU2011253934C1 (en) * | 2004-06-17 | 2013-08-22 | Cytokinetics, Inc. | Substituted urea derivatives for treating cardiac diseases |
| PL216049B1 (pl) | 2004-06-17 | 2014-02-28 | Cytokinetics Inc | Pochodne mocznika, kompozycje zawierajace pochodne mocznika oraz zastosowanie pochodnych mocznika do wytwarzania leku do leczenia niewydolnosci serca |
| GB0512324D0 (en) * | 2005-06-16 | 2005-07-27 | Novartis Ag | Organic compounds |
| DE602005013990D1 (de) | 2004-09-17 | 2009-05-28 | Eisai R&D Man Co Ltd | Medizinische zusammensetzung mit verbesserter stabilität und reduzierten gelierungseigenschaften |
| US7449458B2 (en) | 2005-01-19 | 2008-11-11 | Rigel Pharmaceuticals, Inc. | Prodrugs of 2,4-pyrimidinediamine compounds and their uses |
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| US20070161617A1 (en) | 2005-12-15 | 2007-07-12 | Morgan Bradley P | Certain chemical entities, compositions and methods |
| JP5178526B2 (ja) | 2005-12-19 | 2013-04-10 | サイトキネティクス・インコーポレーテッド | 化合物、組成物および方法 |
| MEP3808A (xx) | 2005-12-21 | 2010-02-10 | Novartis Ag | Derivati pirimidinil aril uree kao fgf inhibitori |
| TW200804349A (en) * | 2005-12-23 | 2008-01-16 | Kalypsys Inc | Novel substituted pyrimidinyloxy ureas as inhibitors of protein kinases |
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| GB0605120D0 (en) | 2006-03-14 | 2006-04-26 | Novartis Ag | Organic Compounds |
| EA200870514A1 (ru) | 2006-05-08 | 2009-04-28 | Ариад Фармасьютикалз, Инк. | Ацетиленовые гетероарильные соединения |
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| ES2548690T3 (es) * | 2006-08-11 | 2015-10-20 | Johns Hopkins University | Secuencias consenso de codificación de cánceres colorrectales humanos |
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| NZ544920A (en) * | 2003-07-23 | 2009-11-27 | Bayer Healthcare Llc | 4{4-[3-(4-chloro-3-trifluoromethylphenyl)-ureido]-3-fluorophenoxy}-pyridine-2-carboxylic acid methylamide and metabolites for the treatment and prevention of diseases and conditions |
-
2004
- 2004-11-26 PE PE2004001167A patent/PE20051046A1/es not_active Application Discontinuation
- 2004-11-26 JP JP2006540401A patent/JP2007515400A/ja not_active Ceased
- 2004-11-26 KR KR1020067010328A patent/KR20060110307A/ko not_active Ceased
- 2004-11-26 BR BRPI0416935-2A patent/BRPI0416935A/pt not_active IP Right Cessation
- 2004-11-26 WO PCT/EP2004/013459 patent/WO2005051366A2/en not_active Ceased
- 2004-11-26 US US10/580,259 patent/US20080312192A1/en not_active Abandoned
- 2004-11-26 TW TW093136547A patent/TW200529849A/zh unknown
- 2004-11-26 RU RU2006122853/04A patent/RU2006122853A/ru unknown
- 2004-11-26 CA CA002546673A patent/CA2546673A1/en not_active Abandoned
- 2004-11-26 EP EP04798101A patent/EP1689376A2/en not_active Withdrawn
- 2004-11-26 AU AU2004292773A patent/AU2004292773A1/en not_active Abandoned
- 2004-11-26 AR ARP040104414A patent/AR047496A1/es unknown
-
2009
- 2009-07-30 AU AU2009203096A patent/AU2009203096A1/en not_active Abandoned
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| Publication number | Publication date |
|---|---|
| WO2005051366A2 (en) | 2005-06-09 |
| KR20060110307A (ko) | 2006-10-24 |
| WO2005051366A3 (en) | 2007-12-21 |
| AU2009203096A1 (en) | 2009-08-20 |
| PE20051046A1 (es) | 2006-01-11 |
| EP1689376A2 (en) | 2006-08-16 |
| AU2004292773A1 (en) | 2005-06-09 |
| TW200529849A (en) | 2005-09-16 |
| JP2007515400A (ja) | 2007-06-14 |
| US20080312192A1 (en) | 2008-12-18 |
| BRPI0416935A (pt) | 2007-01-16 |
| CA2546673A1 (en) | 2005-06-09 |
| AR047496A1 (es) | 2006-01-25 |
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