JP2007515400A - タンパク質キナーゼ依存性疾患の処置におけるジアリール尿素誘導体 - Google Patents
タンパク質キナーゼ依存性疾患の処置におけるジアリール尿素誘導体 Download PDFInfo
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- JP2007515400A JP2007515400A JP2006540401A JP2006540401A JP2007515400A JP 2007515400 A JP2007515400 A JP 2007515400A JP 2006540401 A JP2006540401 A JP 2006540401A JP 2006540401 A JP2006540401 A JP 2006540401A JP 2007515400 A JP2007515400 A JP 2007515400A
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- phenyl
- trifluoromethyl
- mmol
- pyrimidin
- yloxy
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- 239000000196 tragacanth Substances 0.000 description 1
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- 238000000844 transformation Methods 0.000 description 1
- 229960000575 trastuzumab Drugs 0.000 description 1
- 229960001612 trastuzumab emtansine Drugs 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- CFQJBWKKHCMCGJ-UHFFFAOYSA-N tributyl(pyridin-3-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CC=CN=C1 CFQJBWKKHCMCGJ-UHFFFAOYSA-N 0.000 description 1
- 229940078499 tricalcium phosphate Drugs 0.000 description 1
- 235000019731 tricalcium phosphate Nutrition 0.000 description 1
- 229910000391 tricalcium phosphate Inorganic materials 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 230000001228 trophic effect Effects 0.000 description 1
- 230000005747 tumor angiogenesis Effects 0.000 description 1
- 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
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 208000010570 urinary bladder carcinoma Diseases 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 230000006459 vascular development Effects 0.000 description 1
- 229950000578 vatalanib Drugs 0.000 description 1
- JXLYSJRDGCGARV-CFWMRBGOSA-N vinblastine Chemical compound C([C@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-CFWMRBGOSA-N 0.000 description 1
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
- 229960004528 vincristine Drugs 0.000 description 1
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
- GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 description 1
- 229960002066 vinorelbine Drugs 0.000 description 1
- 229940087652 vioxx Drugs 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 229940100445 wheat starch Drugs 0.000 description 1
- 229910000166 zirconium phosphate Inorganic materials 0.000 description 1
- 229940033942 zoladex Drugs 0.000 description 1
- 229940002005 zometa Drugs 0.000 description 1
- CGTADGCBEXYWNE-JUKNQOCSSA-N zotarolimus Chemical compound N1([C@H]2CC[C@@H](C[C@@H](C)[C@H]3OC(=O)[C@@H]4CCCCN4C(=O)C(=O)[C@@]4(O)[C@H](C)CC[C@H](O4)C[C@@H](/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C3)OC)C[C@H]2OC)C=NN=N1 CGTADGCBEXYWNE-JUKNQOCSSA-N 0.000 description 1
- 229950009819 zotarolimus Drugs 0.000 description 1
- OENHQHLEOONYIE-JLTXGRSLSA-N β-Carotene Chemical compound CC=1CCCC(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C OENHQHLEOONYIE-JLTXGRSLSA-N 0.000 description 1
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Classifications
-
- 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
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Health & Medical Sciences (AREA)
- Ceramic Engineering (AREA)
- Manufacturing & Machinery (AREA)
- Inorganic Chemistry (AREA)
- Structural Engineering (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0327734A GB0327734D0 (en) | 2003-11-28 | 2003-11-28 | Organic compounds |
| GB0417805A GB0417805D0 (en) | 2004-08-10 | 2004-08-10 | Organic compounds |
| PCT/EP2004/013459 WO2005051366A2 (en) | 2003-11-28 | 2004-11-26 | Diaryl urea derivatives in the treatment of protein kinase dependent diseases |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2007515400A true JP2007515400A (ja) | 2007-06-14 |
| JP2007515400A5 JP2007515400A5 (https=) | 2008-01-17 |
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| Application Number | Title | Priority Date | Filing Date |
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| JP2006540401A Ceased JP2007515400A (ja) | 2003-11-28 | 2004-11-26 | タンパク質キナーゼ依存性疾患の処置におけるジアリール尿素誘導体 |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US20080312192A1 (https=) |
| EP (1) | EP1689376A2 (https=) |
| JP (1) | JP2007515400A (https=) |
| KR (1) | KR20060110307A (https=) |
| AR (1) | AR047496A1 (https=) |
| AU (2) | AU2004292773A1 (https=) |
| BR (1) | BRPI0416935A (https=) |
| CA (1) | CA2546673A1 (https=) |
| PE (1) | PE20051046A1 (https=) |
| RU (1) | RU2006122853A (https=) |
| TW (1) | TW200529849A (https=) |
| WO (1) | WO2005051366A2 (https=) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011500685A (ja) * | 2007-10-19 | 2011-01-06 | アビラ セラピューティクス， インコーポレイテッド | ヘテロアリール化合物およびその使用 |
| JP2012524123A (ja) * | 2009-04-20 | 2012-10-11 | アビラ セラピューティクス， インコーポレイテッド | へテロアリール化合物およびその使用 |
| JP2012526054A (ja) * | 2009-05-05 | 2012-10-25 | 江▲蘇▼省▲薬▼物研究所有限公司 | 複素環置換のジフェニル尿素類誘導体及びその用途 |
| JP2015525739A (ja) * | 2012-06-26 | 2015-09-07 | クラウン バイオサイエンス インコーポレイテッド（台湾） | 抗癌剤であるシクロプロパンカルボキサミドで置換された芳香族化合物 |
| JP2017535525A (ja) * | 2014-10-01 | 2017-11-30 | レスピバート・リミテツド | Ｐ３８キナーゼ阻害剤としてのジアリール尿素誘導体 |
| JP2021506935A (ja) * | 2017-12-21 | 2021-02-22 | ヘフェイ インスティテューツ オブ フィジカル サイエンス， チャイニーズ アカデミー オブ サイエンシーズ | ピリミジン誘導体系キナーゼ阻害剤類 |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000042012A1 (en) * | 1999-01-13 | 2000-07-20 | Bayer Corporation | φ-CARBOXYARYL SUBSTITUTED DIPHENYL UREAS AS RAF KINASE INHIBITORS |
| JP2006528196A (ja) * | 2003-07-23 | 2006-12-14 | バイエル、ファーマシューテイカルズ、コーポレイション | 病気および状態の処置および防止のためのフロロ置換オメガカルボキシアリールジフェニル尿素 |
| JP2007511203A (ja) * | 2003-05-20 | 2007-05-10 | バイエル、ファーマシューテイカルズ、コーポレイション | キナーゼ阻害活性を有するジアリール尿素 |
| JP4608312B2 (ja) * | 2002-05-29 | 2011-01-12 | ノバルティス アーゲー | プロテインキナーゼ依存性疾患の処置に有用なジアリールウレア誘導体 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU594098B2 (en) * | 1985-12-11 | 1990-03-01 | Ishihara Sangyo Kaisha Ltd. | N-benzoyl urea compounds, antitumorous compositions containing them, and process for their preparation |
| JP3887769B2 (ja) * | 1997-12-22 | 2007-02-28 | バイエル コーポレイション | 対称および非対称ジフェニル尿素を用いるｐ３８キナーゼの阻害 |
| US7928239B2 (en) * | 1999-01-13 | 2011-04-19 | Bayer Healthcare Llc | Inhibition of RAF kinase using quinolyl, isoquinolyl or pyridyl ureas |
| DE60137273D1 (de) * | 2000-10-20 | 2009-02-12 | Eisai R&D Man Co Ltd | Verfahren zur Herstellung von 4-Phenoxy chinolin Derivaten |
| WO2003030908A2 (en) * | 2001-10-09 | 2003-04-17 | The University Of Cincinnati | Inhibitors of the egf receptor for the treatment of thyroid cancer |
| MXPA04007832A (es) * | 2002-02-11 | 2005-09-08 | Bayer Pharmaceuticals Corp | Aril-ureas con actividad inhibitoria de angiogenesis. |
-
2004
- 2004-11-26 JP JP2006540401A patent/JP2007515400A/ja not_active Ceased
- 2004-11-26 WO PCT/EP2004/013459 patent/WO2005051366A2/en not_active Ceased
- 2004-11-26 PE PE2004001167A patent/PE20051046A1/es not_active Application Discontinuation
- 2004-11-26 TW TW093136547A patent/TW200529849A/zh unknown
- 2004-11-26 RU RU2006122853/04A patent/RU2006122853A/ru unknown
- 2004-11-26 KR KR1020067010328A patent/KR20060110307A/ko not_active Ceased
- 2004-11-26 CA CA002546673A patent/CA2546673A1/en not_active Abandoned
- 2004-11-26 AR ARP040104414A patent/AR047496A1/es unknown
- 2004-11-26 EP EP04798101A patent/EP1689376A2/en not_active Withdrawn
- 2004-11-26 BR BRPI0416935-2A patent/BRPI0416935A/pt not_active IP Right Cessation
- 2004-11-26 AU AU2004292773A patent/AU2004292773A1/en not_active Abandoned
- 2004-11-26 US US10/580,259 patent/US20080312192A1/en not_active Abandoned
-
2009
- 2009-07-30 AU AU2009203096A patent/AU2009203096A1/en not_active Abandoned
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000042012A1 (en) * | 1999-01-13 | 2000-07-20 | Bayer Corporation | φ-CARBOXYARYL SUBSTITUTED DIPHENYL UREAS AS RAF KINASE INHIBITORS |
| JP4608312B2 (ja) * | 2002-05-29 | 2011-01-12 | ノバルティス アーゲー | プロテインキナーゼ依存性疾患の処置に有用なジアリールウレア誘導体 |
| JP2007511203A (ja) * | 2003-05-20 | 2007-05-10 | バイエル、ファーマシューテイカルズ、コーポレイション | キナーゼ阻害活性を有するジアリール尿素 |
| JP2006528196A (ja) * | 2003-07-23 | 2006-12-14 | バイエル、ファーマシューテイカルズ、コーポレイション | 病気および状態の処置および防止のためのフロロ置換オメガカルボキシアリールジフェニル尿素 |
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011500685A (ja) * | 2007-10-19 | 2011-01-06 | アビラ セラピューティクス， インコーポレイテッド | ヘテロアリール化合物およびその使用 |
| US8748606B2 (en) | 2007-10-19 | 2014-06-10 | Celgene Avilomics Research, Inc. | 4,6-diaminopyrimidines useful as kinase inhibitors |
| US9040541B2 (en) | 2007-10-19 | 2015-05-26 | Celgene Avilomics Research, Inc. | 4,6-disubstituted pyrimidines useful as kinase inhibitors |
| US9393246B2 (en) | 2007-10-19 | 2016-07-19 | Celgene Avilomics Research, Inc. | 4,6-disubstituted pyrimidines as kinase inhibitors |
| JP2012524123A (ja) * | 2009-04-20 | 2012-10-11 | アビラ セラピューティクス， インコーポレイテッド | へテロアリール化合物およびその使用 |
| JP2012526054A (ja) * | 2009-05-05 | 2012-10-25 | 江▲蘇▼省▲薬▼物研究所有限公司 | 複素環置換のジフェニル尿素類誘導体及びその用途 |
| JP2015525739A (ja) * | 2012-06-26 | 2015-09-07 | クラウン バイオサイエンス インコーポレイテッド（台湾） | 抗癌剤であるシクロプロパンカルボキサミドで置換された芳香族化合物 |
| JP2017008082A (ja) * | 2012-06-26 | 2017-01-12 | クラウン バイオサイエンス インコーポレイテッド（台湾） | 抗癌剤であるシクロプロパンカルボキサミドで置換された芳香族化合物 |
| JP2017535525A (ja) * | 2014-10-01 | 2017-11-30 | レスピバート・リミテツド | Ｐ３８キナーゼ阻害剤としてのジアリール尿素誘導体 |
| JP2021506935A (ja) * | 2017-12-21 | 2021-02-22 | ヘフェイ インスティテューツ オブ フィジカル サイエンス， チャイニーズ アカデミー オブ サイエンシーズ | ピリミジン誘導体系キナーゼ阻害剤類 |
| JP7021356B2 (ja) | 2017-12-21 | 2022-02-16 | ヘフェイ インスティテューツ オブ フィジカル サイエンス， チャイニーズ アカデミー オブ サイエンシーズ | ピリミジン誘導体系キナーゼ阻害剤類 |
| US11602534B2 (en) | 2017-12-21 | 2023-03-14 | Hefei Institutes Of Physical Science, Chinese Academy Of Sciences | Pyrimidine derivative kinase inhibitors |
Also Published As
| Publication number | Publication date |
|---|---|
| EP1689376A2 (en) | 2006-08-16 |
| AR047496A1 (es) | 2006-01-25 |
| PE20051046A1 (es) | 2006-01-11 |
| TW200529849A (en) | 2005-09-16 |
| RU2006122853A (ru) | 2008-01-10 |
| KR20060110307A (ko) | 2006-10-24 |
| WO2005051366A3 (en) | 2007-12-21 |
| BRPI0416935A (pt) | 2007-01-16 |
| CA2546673A1 (en) | 2005-06-09 |
| AU2009203096A1 (en) | 2009-08-20 |
| AU2004292773A1 (en) | 2005-06-09 |
| US20080312192A1 (en) | 2008-12-18 |
| WO2005051366A2 (en) | 2005-06-09 |
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