CN101522683B - 可用作蛋白激酶抑制剂的吡唑并(1,5-a)(1,3,5)三嗪和吡唑并(1,5-a)嘧啶衍生物 - Google Patents
可用作蛋白激酶抑制剂的吡唑并(1,5-a)(1,3,5)三嗪和吡唑并(1,5-a)嘧啶衍生物 Download PDFInfo
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- CN101522683B CN101522683B CN2007800342168A CN200780034216A CN101522683B CN 101522683 B CN101522683 B CN 101522683B CN 2007800342168 A CN2007800342168 A CN 2007800342168A CN 200780034216 A CN200780034216 A CN 200780034216A CN 101522683 B CN101522683 B CN 101522683B
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- amino
- phenyl
- triazine
- pyrazolo
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- 239000007788 liquid Substances 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- CZGIEJXGCLWRPY-UHFFFAOYSA-N n,1-dimethylpyrrolidin-3-amine Chemical compound CNC1CCN(C)C1 CZGIEJXGCLWRPY-UHFFFAOYSA-N 0.000 description 1
- AVAWMINJNRAQFS-UHFFFAOYSA-N n,n-dimethylpyrrolidin-3-amine Chemical compound CN(C)C1CCNC1 AVAWMINJNRAQFS-UHFFFAOYSA-N 0.000 description 1
- 230000017066 negative regulation of growth Effects 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- LFGREXWGYUGZLY-UHFFFAOYSA-N phosphoryl Chemical group [P]=O LFGREXWGYUGZLY-UHFFFAOYSA-N 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- JUXWUYWPUDKPSD-UHFFFAOYSA-N pyrazolo[1,5-a][1,3,5]triazine Chemical compound N1=CN=CN2N=CC=C21 JUXWUYWPUDKPSD-UHFFFAOYSA-N 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 229960001285 quercetin Drugs 0.000 description 1
- 235000005875 quercetin Nutrition 0.000 description 1
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
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- 239000012266 salt solution Substances 0.000 description 1
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- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
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- 238000003786 synthesis reaction Methods 0.000 description 1
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- 229940095064 tartrate Drugs 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
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- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains three hetero rings
- C07D487/16—Peri-condensed systems
-
- 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
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- 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
- A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- 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
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
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- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
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- Communicable Diseases (AREA)
- Oncology (AREA)
- Transplantation (AREA)
- Hospice & Palliative Care (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
化合物 | 名称 | Ki(μM) | IC50 HCT 116 细胞(μM) | IC50 PC-3(μM) |
11a | (11,14)3,5N-{环丙基-吡唑并[1,5- a][1,3,5]三嗪-4-基-氨基}-(2N,4N)- 苯基-1,5-二氮杂-环十四烷-8-酮 | <0.1 | <1 | <1 |
11b | (11,14)3,5N-{异丙基-吡唑并[1,5- a][1,3.5]三嗪-4-基-氨基}-(2N,4N)- 苯基-1,5-二氮杂-环十四烷-8-酮 | |||
11c | (11,14)3,5N-{正丙基-吡唑并[1.5- a][1,3,5]三嗪-4-基-氨基}-(2N,4N)- 苯基-1,5-二氮杂-环十四烷-8-酮 |
化合物 | 名称 | Ki(μM) | IC50 HCT 116 细胞(μM) | IC50 PC-3(μM) |
11d | (11,14)3,5N-{吡啶-3-基-吡唑并 [1,5-a][1,3,5]三嗪-4-基-氨基}- (2N,4N)-苯基-1,5-二氮杂-环十四 烷-8-酮 | <0.1 | <1 | <1 |
11e | (11,14)3,5N-{(3-乙氧基苯基)-吡唑 并[1,5-a][1,3,5]三嗪-4-基-氨基}- (2N,4N)-苯基-1,5-二氮杂-环十四 烷-8-酮 | <0.1 | <1 | <1 |
11f | (11,14)3,5N-{(3-乙氧基羰基苯基)- 吡唑并[1,5-a][1,3,5]三嗪-4-基-氨 基}-(2N,4N)-苯基-1,5-二氮杂-环十 四烷-8-酮 | |||
11g | (11,14)3,5N-{3-(3-{[甲基(1-甲基吡 咯烷-3-基)氨基]羰基}苯基)-吡唑 并[1,5-a][1,3,5]三嗪-4-基-氨基}- (2N,4N)-苯基-1,5-二氮杂-环十四 烷-8-酮 | <0.1 | <1 | <1 |
11h | (11,14)3,5N-{3-(4-甲基哌嗪-1-基羰 基)苯基-吡唑并[1,5-a][1,3,5]三嗪- 4-基-氨基}-(2N,4N)-苯基-1,5-二氮 杂-环十四烷-8-酮 | <0.1 | <1 | <1 |
11i | (11,14)3,5N-{[3-(二甲基氨基)吡咯 烷-1-基]羰基}苯基-吡唑并[1,5- a][1,3,5]三嗪-4-基-氨基}-(2N,4N)- 苯基-1,5-二氮杂-环十四烷-8-酮 | <0.1 | <1 | <1 |
11j | (11,14)3,5N-{4-[(3-{3-(二乙基氨 基)羰基}苯基)氨基]-吡唑并[1,5- a][1,3,5]三嗪-4-基-氨基}-(2N,4N)- 苯基-1,5-二氮杂-环十四烷-8-酮 | <0.1 | <1 | <1 |
11k | (11,14)3,5N-{4-{[3-({[2-(二甲基氨 基)乙基]氨基}羰基)苯基]氨基}-吡 唑并[1,5-a][1,3,5]三嗪-4-基-氨基}- (2N,4N)-苯基-1,5-二氮杂-环十四 烷-8-酮 | <0.1 | <1 | <1 |
化合物 | 名称 | Ki(μM) | IC50 HCT 116 细胞(μM) | IC50 PC-3(μM) |
11l | (11,14)3,5N-{4-({3-[(3-羟基氮杂环 丁烷-1-基)羰基]苯基}氨基)-吡唑 并[1,5-a][1,3,5]三嗪-4-基-氨基}- (2N,4N)-苯基-1,5-二氮杂-环十四 烷-8-酮 | <0.1 | <1 | <1 |
11m | (11,14)3,5N-{[(1-甲基氮杂环丁烷- 3-基)氨基]羰基}苯基)氨基]-吡唑 并[1,5-a][1,3,5]三嗪-4-基-氨基}- (2N,4N)-苯基-1,5-二氮杂-环十四 烷-8-酮 | <0.1 | <1 | <1 |
11n | (11,14)3,5N-{4-[(3-{[[2-(二甲基氨 基)乙基](甲基)氨基]羰基}苯基)氨 基]-吡唑并[1,5-a][1,3,5]三嗪-4-基- 氨基}-(2N,4N)-苯基-1,5-二氮杂-环 十四烷-8-酮 | <0.1 | <1 | <1 |
11o | (11,14)3,5N-{4-[(3-{[甲基(1-甲基 哌啶-4-基)氨基]羰基}苯基)氨基]- 吡唑并[1,5-a][1,3,5]三嗪-4-基-氨 基}-(2N,4N)-苯基-1,5-二氮杂-环十 四烷-8-酮 | <0.1 | <1 | |
11p | (11,14)3,5N-{[(3-{[3-(二乙基氨基) 吡咯烷-1-基]羰基}苯基)-氨基]-吡 唑并[1,5-a][1,3,5]三嗪-4-基-氨基}- (2N,4N)-苯基-1,5-二氮杂-环十四 烷-8-酮 | <0.1 | <1 | <1 |
11q | (11,14)3,5N-{[(3-{[3-(二乙基氨基) 氮杂环丁烷-1-基]羰基}-苯基)-氨 基]-吡唑并[1,5-a][1,3,5]三嗪-4-基- 氨基}-(2N,4N)-苯基-1,5-二氮杂-环 十四烷-8-酮 | <0.1 | <1 | <1 |
11r | (11,14)3,5N-{{[3-(哌嗪-1-基羰基) 苯基]氨基}-吡唑并[1,5-a][1,3,5]三 嗪-4-基-氨基}-(2N,4N)-苯基-1,5- 二氮杂-环十四烷-8-酮 | <0.1 | <1 |
化合物 | 名称 | Ki(μM) | IC50 HCT 116 细胞(μM) | IC50 PC-3(μM) |
11s | (11,14)3,5N-{4-[(3-{[2-(二乙基氨 基)乙基](甲基)-氨基]-羰基}苯基) 氨基]-吡唑并[1,5-a][1,3,5]三嗪-4- 基-氨基}-(2N,4N)-苯基-1,5-二氮 杂-环十四烷-8-酮 | <0.1 | <1 |
化合物 | 名称 | Ki(μM) | IC50 HCT 116 细胞(μM) | IC50 PC-3(μM) |
18a | (11,14)3,5N-{[(3-二甲基氨基- 吡咯烷-1-羰基)-苯-3-基]-吡唑 并-[1,5-a]-嘧啶-2,4-基-二氨基}- (2N,4N)-苯基-1,5-二氮杂-环十 四烷-6-酮 | <0.1 | <3 | <3 |
18b | (11,14)3,5N-{[(3-环丙基]-吡唑 并-[1,5-a]-嘧啶-2,4-基-二氨基}- (2N,4N)-苯基-1,5-二氮杂-环十 四烷-6-酮 | <0.1 | <3 | <3 |
Claims (6)
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US84531406P | 2006-09-18 | 2006-09-18 | |
US60/845,314 | 2006-09-18 | ||
US11/856,476 | 2007-09-17 | ||
US11/856,476 US7517882B2 (en) | 2006-09-18 | 2007-09-17 | Protein kinase inhibitors |
PCT/US2007/020231 WO2008036277A1 (en) | 2006-09-18 | 2007-09-18 | Pyraz0l0(l,5-a) (1, 3, 5) triazine and pyrazolo (1, 5-a) pyrimidine derivatives useful as protein kinase inhibitors |
Publications (2)
Publication Number | Publication Date |
---|---|
CN101522683A CN101522683A (zh) | 2009-09-02 |
CN101522683B true CN101522683B (zh) | 2013-02-27 |
Family
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CN2007800342168A Active CN101522683B (zh) | 2006-09-18 | 2007-09-18 | 可用作蛋白激酶抑制剂的吡唑并(1,5-a)(1,3,5)三嗪和吡唑并(1,5-a)嘧啶衍生物 |
Country Status (12)
Country | Link |
---|---|
US (2) | US7517882B2 (zh) |
EP (1) | EP2064214B1 (zh) |
JP (1) | JP5232786B2 (zh) |
KR (1) | KR101418619B1 (zh) |
CN (1) | CN101522683B (zh) |
AU (1) | AU2007297675B2 (zh) |
BR (1) | BRPI0718459A2 (zh) |
CA (1) | CA2663791C (zh) |
ES (1) | ES2400450T3 (zh) |
HK (1) | HK1135688A1 (zh) |
TW (1) | TWI472530B (zh) |
WO (1) | WO2008036277A1 (zh) |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
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US7517882B2 (en) * | 2006-09-18 | 2009-04-14 | Polaris Group | Protein kinase inhibitors |
CA2720944C (en) * | 2008-04-07 | 2012-12-18 | Irm Llc | Compounds and compositions as kinase inhibitors |
JP6046728B2 (ja) * | 2011-09-30 | 2016-12-21 | オンコデザイン エス.ア. | 大環状flt3キナーゼ阻害剤 |
JP2016510797A (ja) * | 2013-03-15 | 2016-04-11 | オンコデザイン エス.ア. | 大環状塩誘導性キナーゼ阻害剤 |
CN103570728B (zh) * | 2013-11-12 | 2015-12-30 | 山东大学 | 一种取代吡唑并[1,5-a]嘧啶类衍生物及其制备方法与应用 |
CA2978170C (en) * | 2015-03-09 | 2024-02-27 | Aurigene Discovery Technologies Limited | Pyrazolo[1,5-a][1,3,5]triazine and pyrazolo[1,5-a]pyrimidine derivatives as cdk inhibitors |
MX2019001125A (es) * | 2016-07-28 | 2019-06-12 | Tp Therapeutics Inc | Inhibidores de cinasa macrociclica. |
Citations (1)
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CN1826343A (zh) * | 2003-05-22 | 2006-08-30 | 法玛西雅意大利公司 | 吡唑并-喹唑啉衍生物、它们的制备方法和它们作为激酶抑制剂的用途 |
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DE10255343B4 (de) | 2002-11-27 | 2006-09-07 | Nad Ag | N,N-Verbrückte, Stickstoff-Substituierte Carbacyclische Indolocarbazole als Proteinkinase-Inhibitoren |
AU2005250285B2 (en) | 2004-06-02 | 2011-08-18 | Takeda Pharmaceutical Company Limited | Fused heterocyclic compound |
US7517882B2 (en) * | 2006-09-18 | 2009-04-14 | Polaris Group | Protein kinase inhibitors |
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- 2007-09-18 KR KR1020097005501A patent/KR101418619B1/ko active IP Right Grant
- 2007-09-18 CA CA2663791A patent/CA2663791C/en not_active Expired - Fee Related
- 2007-09-18 WO PCT/US2007/020231 patent/WO2008036277A1/en active Application Filing
- 2007-09-18 AU AU2007297675A patent/AU2007297675B2/en not_active Ceased
- 2007-09-18 EP EP07838443A patent/EP2064214B1/en not_active Not-in-force
- 2007-09-18 JP JP2009528344A patent/JP5232786B2/ja not_active Expired - Fee Related
- 2007-09-18 CN CN2007800342168A patent/CN101522683B/zh active Active
- 2007-09-18 ES ES07838443T patent/ES2400450T3/es active Active
- 2007-09-18 BR BRPI0718459-0A patent/BRPI0718459A2/pt not_active Application Discontinuation
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- 2009-03-03 US US12/396,919 patent/US20090247501A1/en not_active Abandoned
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CN1826343A (zh) * | 2003-05-22 | 2006-08-30 | 法玛西雅意大利公司 | 吡唑并-喹唑啉衍生物、它们的制备方法和它们作为激酶抑制剂的用途 |
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AU2007297675B2 (en) | 2012-09-20 |
CA2663791C (en) | 2015-11-03 |
TWI472530B (zh) | 2015-02-11 |
CN101522683A (zh) | 2009-09-02 |
ES2400450T3 (es) | 2013-04-10 |
WO2008036277A1 (en) | 2008-03-27 |
KR20090083889A (ko) | 2009-08-04 |
TW200837065A (en) | 2008-09-16 |
CA2663791A1 (en) | 2008-03-27 |
HK1135688A1 (en) | 2010-06-11 |
US20080070893A1 (en) | 2008-03-20 |
US7517882B2 (en) | 2009-04-14 |
US20090247501A1 (en) | 2009-10-01 |
EP2064214A1 (en) | 2009-06-03 |
KR101418619B1 (ko) | 2014-07-14 |
EP2064214B1 (en) | 2013-01-30 |
BRPI0718459A2 (pt) | 2013-12-03 |
JP2010503690A (ja) | 2010-02-04 |
JP5232786B2 (ja) | 2013-07-10 |
AU2007297675A1 (en) | 2008-03-27 |
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