JP5368701B2 - ｃ−Ｍｅｔモジュレーター及び使用方法 - Google Patents
ｃ−Ｍｅｔモジュレーター及び使用方法 Download PDFInfo
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- JP5368701B2 JP5368701B2 JP2007520386A JP2007520386A JP5368701B2 JP 5368701 B2 JP5368701 B2 JP 5368701B2 JP 2007520386 A JP2007520386 A JP 2007520386A JP 2007520386 A JP2007520386 A JP 2007520386A JP 5368701 B2 JP5368701 B2 JP 5368701B2
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- alkyl
- optionally substituted
- compound
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- 230000000694 effects Effects 0.000 claims abstract description 60
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- 102000020233 phosphotransferase Human genes 0.000 claims abstract description 50
- 150000003839 salts Chemical class 0.000 claims abstract description 23
- 125000000217 alkyl group Chemical group 0.000 claims description 117
- 239000003795 chemical substances by application Substances 0.000 claims description 51
- 125000000623 heterocyclic group Chemical group 0.000 claims description 47
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 39
- 101100335081 Mus musculus Flt3 gene Proteins 0.000 claims description 37
- 125000003118 aryl group Chemical group 0.000 claims description 35
- 229910052757 nitrogen Inorganic materials 0.000 claims description 25
- 229910052736 halogen Inorganic materials 0.000 claims description 20
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- 125000003107 substituted aryl group Chemical group 0.000 claims description 20
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- 238000012216 screening Methods 0.000 claims description 11
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- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 8
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- 229910052731 fluorine Inorganic materials 0.000 claims description 4
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- 229910052698 phosphorus Inorganic materials 0.000 claims description 2
- YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Natural products C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 claims 4
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 24
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 23
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- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 20
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 20
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- 150000003254 radicals Chemical class 0.000 description 18
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- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 16
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- 239000003446 ligand Substances 0.000 description 16
- 235000018102 proteins Nutrition 0.000 description 16
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- 102000001253 Protein Kinase Human genes 0.000 description 15
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 15
- 108060006633 protein kinase Proteins 0.000 description 15
- 239000000741 silica gel Substances 0.000 description 15
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- 229910052938 sodium sulfate Inorganic materials 0.000 description 14
- 235000011152 sodium sulphate Nutrition 0.000 description 14
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 13
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Classifications
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/52—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring condensed with a ring other than six-membered
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
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- C07D473/30—Oxygen atom attached in position 6, e.g. hypoxanthine
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/04—Ortho-condensed systems
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/12—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains three hetero rings
- C07D493/14—Ortho-condensed systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/12—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains three hetero rings
- C07D493/20—Spiro-condensed systems
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US58497704P | 2004-07-02 | 2004-07-02 | |
| US60/584,977 | 2004-07-02 | ||
| PCT/US2005/023364 WO2006014325A2 (en) | 2004-07-02 | 2005-07-01 | C-met modulators and method of use |
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| Publication Number | Publication Date |
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| JP2008505181A JP2008505181A (ja) | 2008-02-21 |
| JP2008505181A5 JP2008505181A5 (https=) | 2008-08-21 |
| JP5368701B2 true JP5368701B2 (ja) | 2013-12-18 |
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| JP2007520386A Expired - Fee Related JP5368701B2 (ja) | 2004-07-02 | 2005-07-01 | ｃ−Ｍｅｔモジュレーター及び使用方法 |
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|---|---|
| US (1) | US7977345B2 (https=) |
| EP (1) | EP1773826A4 (https=) |
| JP (1) | JP5368701B2 (https=) |
| AU (1) | AU2005270068B2 (https=) |
| CA (1) | CA2572331A1 (https=) |
| WO (1) | WO2006014325A2 (https=) |
Families Citing this family (116)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2210607B1 (en) * | 2003-09-26 | 2011-08-17 | Exelixis Inc. | N-[3-fluoro-4-({6-(methyloxy)-7-[(3-morpholin-4-ylpropyl)oxy]quinolin-4-yl}oxy)phenyl]-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide for the treatment of cancer |
| US7531532B2 (en) | 2004-02-27 | 2009-05-12 | Eisai R&D Management Co., Ltd. | Pyridine derivative and pyrimidine derivative |
| ES2438017T3 (es) | 2004-07-30 | 2014-01-15 | Methylgene Inc. | Inhibidores de la señalización del receptor del VEGF y del receptor del HGF |
| KR101378716B1 (ko) * | 2005-05-20 | 2014-04-10 | 메틸진 인코포레이티드 | Ｖｅｇｆ 수용체 및 ｈｇｆ 수용체 신호전달의 억제제 |
| AU2006313456B2 (en) | 2005-05-20 | 2011-06-23 | Methylgene Inc. | Inhibitors of VEGF receptor and HGF receptor signaling |
| CA2607699A1 (en) * | 2005-06-02 | 2006-12-07 | Galaxy Biotech, Llc | Methods of treating brain tumors with antibodies |
| CN101198590B (zh) | 2005-08-24 | 2012-05-09 | 卫材R&D管理有限公司 | 吡啶衍生物及嘧啶衍生物（3） |
| PT1940844E (pt) * | 2005-10-28 | 2010-01-06 | Scripps Research Inst | Compostos e composições como inibidores de proteína-quinase |
| NL2000291C2 (nl) | 2005-11-10 | 2009-02-17 | Pfizer Prod Inc | 1-(1-(2-ethoxyethyl)-3-ethyl-7-(4-methylpyridin-2-ylamino)-1H- pyrazool(4,3-d)pyrimidine-5-yl)piperidine-4-carbonzuur en zouten daarvan. |
| JP2009526761A (ja) | 2006-01-30 | 2009-07-23 | アレイ バイオファーマ、インコーポレイテッド | ヘテロ二環式チオフェン化合物および使用の方法 |
| WO2007103308A2 (en) | 2006-03-07 | 2007-09-13 | Array Biopharma Inc. | Heterobicyclic pyrazole compounds and methods of use |
| AR059922A1 (es) * | 2006-04-01 | 2008-05-07 | Galaxy Biotech Llc | Anticuerpos monoclonales humanizados para el factor de crecimiento de hepatocitos |
| CA2651898A1 (en) | 2006-04-07 | 2007-10-18 | Develogen Aktiengesellschaft | Thienopyrimidines having mnk1/mnk2 inhibiting activity for pharmaceutical compositions |
| JP2009539878A (ja) * | 2006-06-08 | 2009-11-19 | アレイ バイオファーマ、インコーポレイテッド | キノリン化合物および使用方法 |
| EP1889847A1 (en) | 2006-07-10 | 2008-02-20 | DeveloGen Aktiengesellschaft | Pyrrolopyrimidines for pharmaceutical compositions |
| EP2057164A1 (en) | 2006-08-07 | 2009-05-13 | Incyte Corporation | Triazolotriazines as kinase inhibitors |
| CA2661333C (en) * | 2006-08-23 | 2014-08-05 | Eisai R&D Management Co., Ltd. | Salt of phenoxypyridine derivative or crystal thereof and process for producing the same |
| US7790885B2 (en) | 2006-08-31 | 2010-09-07 | Eisai R&D Management Co., Ltd. | Process for preparing phenoxypyridine derivatives |
| JP2010507618A (ja) * | 2006-10-27 | 2010-03-11 | グラクソ グループ リミテッド | ｃ−Ｍｅｔキナーゼ阻害薬としての７−アザインドール誘導体 |
| RS54510B1 (sr) | 2006-11-22 | 2016-06-30 | Incyte Holdings Corporation | Imidazotriazini i imidazopirimidini kao inhibitori kinaze |
| NZ577197A (en) | 2006-12-08 | 2011-02-25 | Irm Llc | Pyrimidine compounds especially 4-phenylamino-2-arylamino-pyrimidine derivatives and compositions as protein kinase inhibitors |
| DE102007026341A1 (de) | 2007-06-06 | 2008-12-11 | Merck Patent Gmbh | Benzoxazolonderivate |
| CN101918403A (zh) * | 2007-09-06 | 2010-12-15 | 阵列生物制药公司 | 作为酪氨酸激酶抑制剂的吡唑并吡啶类化合物 |
| JP2009132660A (ja) | 2007-11-30 | 2009-06-18 | Eisai R & D Management Co Ltd | 食道癌治療用組成物 |
| NZ588355A (en) | 2008-03-05 | 2012-03-30 | Methylgene Inc | Inhibitors of protein tyrosine kinase activity |
| TWI472529B (zh) | 2008-05-21 | 2015-02-11 | Incyte Corp | ２－氟－Ｎ－甲基－４－〔７－（喹啉－６－基－甲基）－咪唑并〔１，２－ｂ〕〔１，２，４〕三－２－基〕苯甲醯胺之鹽類及其相關製備方法 |
| KR101335843B1 (ko) * | 2008-08-20 | 2013-12-02 | 조에티스 엘엘씨 | 피롤로[2,3-ｄ]피리미딘 화합물 |
| UY32072A (es) | 2008-08-26 | 2010-03-26 | Boehringer Ingelheim Int | Tienopirimidinas para composiciones farmacéuticas |
| ES2599458T3 (es) * | 2008-10-14 | 2017-02-01 | Sunshine Lake Pharma Co., Ltd. | Compuestos y métodos de uso |
| DE102009003975A1 (de) | 2009-01-07 | 2010-07-08 | Merck Patent Gmbh | Benzothiazolonderivate |
| NZ779754A (en) | 2009-01-16 | 2023-04-28 | Exelixis Inc | Malate salt of n-(4-{ [6,7-bis(methyloxy)quinolin-4-yl] oxy} phenyl)-n’-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide, and crystalline forms thereof for the treatment of cancer |
| EP2408300B1 (en) * | 2009-03-21 | 2016-05-11 | Sunshine Lake Pharma Co., Ltd. | Amino ester derivatives, salts thereof and methods of use |
| EP2245936A1 (en) | 2009-04-27 | 2010-11-03 | Bayer CropScience AG | Use of 4-aza indole derivatives for the reduction of mycotoxin contamination |
| UA108618C2 (uk) | 2009-08-07 | 2015-05-25 | Застосування c-met-модуляторів в комбінації з темозоломідом та/або променевою терапією для лікування раку | |
| ES2426407T3 (es) * | 2009-10-15 | 2013-10-23 | Pfizer Inc. | Compuestos de pirrolo[2,3-d]pirimidina |
| DE102009056886A1 (de) | 2009-12-03 | 2011-06-09 | Bayer Schering Pharma Aktiengesellschaft | cMet-Inhibitoren zur Behandlung der Endometriose |
| MX2012008898A (es) | 2010-02-03 | 2012-11-06 | Incyte Corp | Imidazo - [1, 2 - b] [1, 2, 4] triazinas como inhibidores de c - met. |
| UY33241A (es) | 2010-02-26 | 2011-09-30 | Boehringer Ingelheim Int | ?Tienopirimidinas que contienen heterocicloalquilo para composiciones farmacéuticas?. |
| MX2012009851A (es) | 2010-02-26 | 2012-09-12 | Boehringer Ingelheim Int | Tienopirimidinas que contienen un grupo alquilo sustituido para composiciones farmaceuticas. |
| JP5575274B2 (ja) | 2010-02-26 | 2014-08-20 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 医薬組成物のためのｍｎｋｌ／ｍｎｋ２阻害活性を有する４−［シクロアルキルオキシ（ヘテロ）アリールアミノ］チエノ「２，３−ｄ］ピリミジン |
| NZ604306A (en) | 2010-05-17 | 2015-02-27 | Incozen Therapeutics Pvt Ltd | Novel 3,5-disubstitued-3h-imidazo[4,5-b]pyridine and 3,5- disubstitued -3h-[1,2,3]triazolo[4,5-b] pyridine compounds as modulators of protein kinases |
| US9073918B2 (en) | 2010-05-20 | 2015-07-07 | Takeda Pharmaceutical Company Limited | Pyrazolo[4,3-b]pyridine-7-amine inhibitors of ALK5 |
| CN102958523B (zh) | 2010-06-25 | 2014-11-19 | 卫材R&D管理有限公司 | 使用具有激酶抑制作用的组合的抗肿瘤剂 |
| EA030435B1 (ru) | 2010-07-16 | 2018-08-31 | Экселиксис, Инк. | ТАБЛЕТКА, СОДЕРЖАЩАЯ МОДУЛЯТОР c-MET В ФОРМЕ КРИСТАЛЛИЧЕСКОЙ L-МАЛАТНОЙ СОЛИ (ВАРИАНТЫ), СПОСОБ ЕЕ ПРОИЗВОДСТВА И СПОСОБ ЛЕЧЕНИЯ ОНКОЛОГИЧЕСКОГО ЗАБОЛЕВАНИЯ С ЕЕ ИСПОЛЬЗОВАНИЕМ |
| MX352926B (es) | 2010-09-27 | 2017-12-14 | Exelixis Inc | Inhibidores dobles de met y factor de crecimiento endotelial vascular (vegf) para el tratamiento de cancer de prostata resistente a la castracion y metastasis osteoblasticas en los huesos. |
| EP2637692A4 (en) | 2010-11-12 | 2014-09-10 | Scott & White Healthcare | ANTIBODIES TO THE ENDOTHELIAL TUMOR MARKER 8 |
| BR112013020362A2 (pt) | 2011-02-10 | 2018-05-29 | Exelixis Inc | processos para a preparação de compostos de quinolina, compostos e combinações farmacêuticas que os contem |
| US20120252840A1 (en) | 2011-04-04 | 2012-10-04 | Exelixis, Inc. | Method of Treating Cancer |
| MX2013012695A (es) | 2011-05-02 | 2014-03-27 | Exelixis Inc | Metodo para el tratamiento del cancer y el dolor por cancer de hueso. |
| US8772277B2 (en) | 2011-08-04 | 2014-07-08 | Takeda Pharmaceutical Company Limited | Nitrogen-containing heterocyclic compound |
| EP2758402B9 (en) | 2011-09-22 | 2016-09-14 | Pfizer Inc | Pyrrolopyrimidine and purine derivatives |
| EP2758057B1 (en) | 2011-09-22 | 2017-05-31 | Exelixis, Inc. | Method for treating osteoporosis |
| CN104395284A (zh) | 2011-10-20 | 2015-03-04 | 埃克塞里艾克西斯公司 | 制备喹啉衍生物的方法 |
| US9464089B2 (en) | 2012-01-13 | 2016-10-11 | Acea Biosciences Inc. | Heterocyclic compounds and uses thereof |
| WO2013106792A1 (en) | 2012-01-13 | 2013-07-18 | Acea Biosciences Inc. | Heterocyclic compounds and uses as anticancer agents. |
| US9034885B2 (en) | 2012-01-13 | 2015-05-19 | Acea Biosciences Inc. | EGFR modulators and uses thereof |
| US9586965B2 (en) | 2012-01-13 | 2017-03-07 | Acea Biosciences Inc. | Pyrrolo[2,3-d]pyrimidine compounds as inhibitors of protein kinases |
| CN107082779A (zh) | 2012-03-30 | 2017-08-22 | 理森制药股份公司 | 作为c‑met 蛋白激酶调节剂的新化合物 |
| WO2013152252A1 (en) | 2012-04-06 | 2013-10-10 | OSI Pharmaceuticals, LLC | Combination anti-cancer therapy |
| WO2013166296A1 (en) | 2012-05-02 | 2013-11-07 | Exelixis, Inc. | A dual met - vegf modulator for treating osteolytic bone metastases |
| CN104507930B (zh) * | 2012-06-29 | 2017-10-10 | 贝达药业股份有限公司 | 作为c‑Met酪氨酸激酶抑制剂的新型稠合吡啶衍生物 |
| TWI520962B (zh) * | 2012-06-29 | 2016-02-11 | As the c-Met tyrosine kinase inhibitors novel fused pyridine derivatives | |
| CN103570723B (zh) * | 2012-07-27 | 2016-07-13 | 广西梧州制药（集团）股份有限公司 | 吡唑并嘧啶衍生物及其制备方法和在药物制备中的用途 |
| AU2013343105B2 (en) | 2012-11-08 | 2016-04-14 | Pfizer Inc. | Heteroaromatic compounds as dopamine D1 ligands |
| CN102964308B (zh) * | 2012-11-30 | 2015-03-18 | 中国药科大学 | 新型嘧啶类化合物、其制备方法、包含此类化合物的药物组合物及其用途 |
| KR20150098605A (ko) | 2012-12-21 | 2015-08-28 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 퀴놀린 유도체의 비정질 형태 및 그의 제조방법 |
| CA2907334C (en) | 2013-03-15 | 2021-12-07 | Exelixis, Inc. | Metabolites of n-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-n'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide |
| US11564915B2 (en) | 2013-04-04 | 2023-01-31 | Exelixis, Inc. | Cabozantinib dosage form and use in the treatment of cancer |
| WO2014165779A1 (en) * | 2013-04-04 | 2014-10-09 | Exelixis, Inc. | Drug combinations to treat cancer |
| NZ714049A (en) | 2013-05-14 | 2020-05-29 | Eisai R&D Man Co Ltd | Biomarkers for predicting and assessing responsiveness of endometrial cancer subjects to lenvatinib compounds |
| KR102173433B1 (ko) | 2013-07-11 | 2020-11-04 | 에이시아 바이오사이언시스 인코포레이티드. | 키나아제 억제제로써의 피리미딘 유도체 |
| BR112016018450A2 (pt) | 2014-02-14 | 2018-09-18 | Exelixis Inc | formas sólidas cristalinas de n-{4-[(6,7-dimetoxiquinolin-4-il)oxi]fenil}-n'-(4-fluorofenil)ciclopropano-1,1-dicarboxamida, processos de preparo e métodos de uso |
| RU2016141385A (ru) | 2014-03-24 | 2018-04-28 | Дженентек, Инк. | Лечение рака антагонистами с-мет и их корреляция с экспрессией hgf |
| WO2015162515A1 (en) | 2014-04-25 | 2015-10-29 | Pfizer Inc. | Heteroaromatic compounds and their use as dopamine d1 ligands |
| EP3134405B1 (en) | 2014-04-25 | 2019-08-28 | Pfizer Inc | Heteroaromatic compounds and their use as dopamine d1 ligands |
| EP3174854B1 (en) | 2014-07-31 | 2022-08-24 | Exelixis, Inc. | Method of preparing fluorine-18 labeled cabozantinib and its analogs |
| MX382904B (es) | 2014-08-05 | 2025-03-13 | Exelixis Inc | Combinaciones de fármacos para tratar mieloma múltiple. |
| PT3524595T (pt) | 2014-08-28 | 2022-09-19 | Eisai R&D Man Co Ltd | Derivado de quinolina altamente puro e método para produção do mesmo |
| LT3263106T (lt) | 2015-02-25 | 2024-01-10 | Eisai R&D Management Co., Ltd. | Chinolino darinių kartumo sumažinimo būdas |
| KR102662228B1 (ko) | 2015-03-04 | 2024-05-02 | 머크 샤프 앤드 돔 코포레이션 | 암을 치료하기 위한 pd-1 길항제 및 vegfr/fgfr/ret 티로신 키나제 억제제의 조합 |
| MX373231B (es) | 2015-06-16 | 2020-05-08 | Eisai R&D Man Co Ltd | Agente anticancerigeno. |
| EP3292115B1 (en) * | 2015-07-20 | 2019-12-25 | Betta Pharmaceuticals Co., Ltd. | Crystalline form of fused pyridine derivative's maleate and uses thereof |
| CA3030582A1 (en) | 2015-07-22 | 2017-01-26 | The Royal Institution For The Advancement Of Learning/Mcgill University | Compounds and uses thereof in the treatment of cancers and other medical conditions |
| US12220398B2 (en) | 2015-08-20 | 2025-02-11 | Eisai R&D Management Co., Ltd. | Tumor therapeutic agent |
| JP6889494B2 (ja) | 2015-10-09 | 2021-06-18 | エイシア セラピューティクス， インコーポレイテッド | ピロロピリミジンキナーゼ阻害剤の薬学的塩、物理的形態、および組成物、ならびにそれらを作製する方法 |
| GB201520499D0 (en) | 2015-11-20 | 2016-01-06 | Medical Res Council Technology | Compounds |
| GB201520500D0 (en) | 2015-11-20 | 2016-01-06 | Medical Res Council Technology | Compounds |
| EP3442531A1 (en) | 2016-04-15 | 2019-02-20 | Exelixis, Inc. | Method of treating renal cell carcinoma using n-(4-(6,7-dimethoxyquinolin-4-yloxy) phenyl)-n'-(4-fluoropheny)cyclopropane-1,1-dicarboxamide, (2s)-hydroxybutanedioate |
| CN106496232B (zh) * | 2016-09-22 | 2018-11-09 | 南方医科大学 | 一种具有抗肿瘤活性的1-(2-四氢吡喃)-1H-吡唑并[3,4-d]嘧啶类化合物及其制备方法 |
| US12303505B2 (en) | 2017-02-08 | 2025-05-20 | Eisai R&D Management Co., Ltd. | Tumor-treating pharmaceutical composition |
| AU2017408099A1 (en) | 2017-04-07 | 2019-11-07 | ACEA Therapeutics, Inc. | Pharmaceutical salts, physical forms, and compositions of pyrrolopyrimidine kinase inhibitors, and methods of making same |
| RU2019134940A (ru) | 2017-05-16 | 2021-06-16 | Эйсай Ар Энд Ди Менеджмент Ко., Лтд. | Лечение гепатоцеллюлярной карциномы |
| EP3638669A1 (en) | 2017-06-13 | 2020-04-22 | Bayer Pharma Aktiengesellschaft | Substituted pyrrolopyridine-derivatives |
| EP3638670B1 (en) | 2017-06-13 | 2021-07-21 | Bayer Pharma Aktiengesellschaft | Substituted pyrrolopyridine-derivatives as map4k1 modulators for the treatment of cancer diseases |
| WO2018228925A1 (en) | 2017-06-13 | 2018-12-20 | Bayer Pharma Aktiengesellschaft | Substituted pyrrolopyridine-derivatives |
| CA3070013A1 (en) | 2017-07-18 | 2019-01-24 | Bayer Pharma Aktiengesellschaft | Substituted pyrrolopyridine-derivatives |
| IL276398B2 (en) | 2018-01-31 | 2026-03-01 | Deciphera Pharmaceuticals Llc | Combination therapy for mastocytosis |
| CN118416236A (zh) | 2018-01-31 | 2024-08-02 | 德西费拉制药有限责任公司 | 治疗胃肠道间质瘤的组合疗法 |
| TWI831259B (zh) | 2018-06-15 | 2024-02-01 | 漢達生技醫藥股份有限公司 | 包含達沙替尼十二烷基硫酸鹽組合物的膠囊 |
| UY38349A (es) | 2018-08-30 | 2020-03-31 | Array Biopharma Inc | Compuestos de pirazolo[3,4-b]piridina como inhibidores de cinasas tam y met |
| WO2020120257A1 (en) | 2018-12-11 | 2020-06-18 | Bayer Aktiengesellschaft | Substituted pyrrolopyridine-derivatives |
| WO2020132384A1 (en) | 2018-12-21 | 2020-06-25 | Celgene Corporation | Thienopyridine inhibitors of ripk2 |
| NL2022471B1 (en) | 2019-01-29 | 2020-08-18 | Vationpharma B V | Solid state forms of oclacitinib |
| WO2020185812A1 (en) | 2019-03-11 | 2020-09-17 | Teva Pharmaceuticals International Gmbh | Solid state forms of ripretinib |
| CN114466847A (zh) * | 2019-06-25 | 2022-05-10 | 西诺普塞疗法公司 | 用于治疗癌症的化合物 |
| TWI878335B (zh) | 2019-08-12 | 2025-04-01 | 美商迪賽孚爾製藥有限公司 | 治療胃腸道基質瘤方法 |
| EP4013412B1 (en) | 2019-08-12 | 2026-01-28 | Deciphera Pharmaceuticals, LLC | Ripretinib for treating gastrointestinal stromal tumors |
| EP4084779B1 (en) | 2019-12-30 | 2024-10-09 | Deciphera Pharmaceuticals, LLC | Compositions of 1-(4-bromo-5-(1-ethyl-7-(methylamino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluorophenyl)-3-phenylurea |
| MX2022008103A (es) | 2019-12-30 | 2022-09-19 | Deciphera Pharmaceuticals Llc | Formulaciones de inhibidores de la cinasa amorfa y metodos de estas. |
| WO2021249913A1 (en) | 2020-06-09 | 2021-12-16 | Bayer Aktiengesellschaft | 2'-(quinolin-3-yl)-5',6'-dihydrospiro[azetidine-3,4'-pyrrolo[1,2-b]pyrazole]-1-carboxylate derivatives and related compounds as map4k1 (hpk1) inhibitors for the treatment of cancer |
| US20240174683A1 (en) | 2021-02-05 | 2024-05-30 | Bayer Aktiengesellschaft | Map4k1 inhibitors |
| CN116836176B (zh) * | 2022-03-23 | 2026-02-24 | 中国科学院上海药物研究所 | 青蒿素类化合物、其制备方法和应用 |
| CN115160340B (zh) * | 2022-06-07 | 2023-07-21 | 四川大学华西医院 | 一种具有ack1抑制活性的小分子化合物及其应用 |
| US11779572B1 (en) | 2022-09-02 | 2023-10-10 | Deciphera Pharmaceuticals, Llc | Methods of treating gastrointestinal stromal tumors |
| US20260049059A1 (en) * | 2022-11-25 | 2026-02-19 | Synthon B.V. | A process for preparation of cabozantinib or tivozanib |
| WO2024163400A1 (en) | 2023-01-31 | 2024-08-08 | Handa Oncology, Llc | Improved cabozantinib compositions and methods of use |
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| US3149111A (en) * | 1961-09-29 | 1964-09-15 | Burroughs Wellcome Co | Dinitrophenylmercaptopurines |
| IL112249A (en) * | 1994-01-25 | 2001-11-25 | Warner Lambert Co | Pharmaceutical compositions containing di and tricyclic pyrimidine derivatives for inhibiting tyrosine kinases of the epidermal growth factor receptor family and some new such compounds |
| GB9604361D0 (en) * | 1996-02-29 | 1996-05-01 | Pharmacia Spa | 4-Substituted pyrrolopyrimidine compounds as tyrosine kinase inhibitors |
| US6107300A (en) | 1996-03-27 | 2000-08-22 | Dupont Pharmaceuticals | Arylamino fused pyrimidines |
| CA2390948A1 (en) * | 1999-06-03 | 2000-12-14 | Abbott Laboratories | Cell adhesion-inhibiting antiinflammatory compounds |
| AU2223201A (en) * | 1999-12-24 | 2001-07-09 | Kirin Beer Kabushiki Kaisha | Quinoline and quinazoline derivatives and drugs containing the same |
| AU9598601A (en) * | 2000-10-20 | 2002-04-29 | Eisai Co Ltd | Nitrogenous aromatic ring compounds |
| AU2002313249B2 (en) * | 2001-06-22 | 2008-08-21 | Kirin Pharma Kabushiki Kaisha | Quinoline derivative and quinazoline derivate inhibiting self-phosphorylation of hepatocytus proliferator receptor, and medicinal composition containing the same |
| JP4224979B2 (ja) * | 2002-04-09 | 2009-02-18 | 大正製薬株式会社 | インターロイキン１２抑制剤 |
| RU2004135386A (ru) * | 2002-05-06 | 2005-07-20 | Вертекс Фармасьютикалз Инкорпорейтед (Us) | Тиадиазолы или оксадиазолы и их применение в качестве ингибиторов протеинкиназы jak |
| GB0219746D0 (en) * | 2002-08-23 | 2002-10-02 | Inst Of Ex Botany Ascr | Azapurine derivatives |
| EP1641759B1 (en) * | 2003-07-07 | 2014-03-12 | Merck Patent GmbH | Malonamide derivatives |
| US7439246B2 (en) * | 2004-06-28 | 2008-10-21 | Bristol-Myers Squibb Company | Fused heterocyclic kinase inhibitors |
| US7173031B2 (en) * | 2004-06-28 | 2007-02-06 | Bristol-Myers Squibb Company | Pyrrolotriazine kinase inhibitors |
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- 2005-07-01 JP JP2007520386A patent/JP5368701B2/ja not_active Expired - Fee Related
- 2005-07-01 EP EP05763620A patent/EP1773826A4/en not_active Withdrawn
- 2005-07-01 AU AU2005270068A patent/AU2005270068B2/en not_active Ceased
- 2005-07-01 WO PCT/US2005/023364 patent/WO2006014325A2/en not_active Ceased
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| WO2006014325A2 (en) | 2006-02-09 |
| US7977345B2 (en) | 2011-07-12 |
| AU2005270068A1 (en) | 2006-02-09 |
| AU2005270068B2 (en) | 2012-04-19 |
| WO2006014325A3 (en) | 2007-03-01 |
| EP1773826A4 (en) | 2009-06-03 |
| CA2572331A1 (en) | 2006-02-09 |
| JP2008505181A (ja) | 2008-02-21 |
| EP1773826A2 (en) | 2007-04-18 |
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