CA2572331A1 - C-met modulators and method of use - Google Patents
C-met modulators and method of use Download PDFInfo
- Publication number
- CA2572331A1 CA2572331A1 CA002572331A CA2572331A CA2572331A1 CA 2572331 A1 CA2572331 A1 CA 2572331A1 CA 002572331 A CA002572331 A CA 002572331A CA 2572331 A CA2572331 A CA 2572331A CA 2572331 A1 CA2572331 A1 CA 2572331A1
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- Prior art keywords
- optionally substituted
- compound according
- 6alkyl
- mmol
- ring system
- Prior art date
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- Abandoned
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Classifications
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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
- C07D471/04—Ortho-condensed systems
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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
- C07D473/28—Oxygen atom
- C07D473/30—Oxygen atom attached in position 6, e.g. hypoxanthine
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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
- C07D473/32—Nitrogen atom
-
- 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
- C07D493/02—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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- 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
- C07D493/14—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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| CA2572331A1 true CA2572331A1 (en) | 2006-02-09 |
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| Application Number | Title | Priority Date | Filing Date |
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| CA002572331A Abandoned CA2572331A1 (en) | 2004-07-02 | 2005-07-01 | C-met modulators and method of use |
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| US (1) | US7977345B2 (enExample) |
| EP (1) | EP1773826A4 (enExample) |
| JP (1) | JP5368701B2 (enExample) |
| AU (1) | AU2005270068B2 (enExample) |
| CA (1) | CA2572331A1 (enExample) |
| WO (1) | WO2006014325A2 (enExample) |
Families Citing this family (116)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SI2392564T1 (sl) * | 2003-09-26 | 2014-02-28 | Exelixis, Inc. | c-Met modulatorji in postopki uporabe |
| US20070270421A1 (en) | 2004-02-27 | 2007-11-22 | Tomohiro Matsushima | Novel pyridine Derivative and Pyrimidine Derivative (1) |
| MX2007001216A (es) * | 2004-07-30 | 2007-03-23 | Methylgene Inc | Inhibidores de la senalizacion del receptor del factor de crecimiento endotelial vascular y del receptor del factor de crecimiento del hepatocito. |
| MX2007014617A (es) | 2005-05-20 | 2008-02-11 | Methylgene Inc | Inhibidores de senalizacion de receptor de factor de crecimiento endotelial bascular y receptor de factor de crecimiento de hepatocitos. |
| CA2611370C (en) * | 2005-05-20 | 2014-11-25 | Oscar Mario Saavedra | Inhibitors of vegf receptor and hgf receptor signaling |
| KR20080026562A (ko) * | 2005-06-02 | 2008-03-25 | 갤럭시 바이오테크, 엘엘씨 | 항체를 이용한 뇌종양 치료 방법 |
| DK1889836T3 (da) | 2005-08-24 | 2013-08-19 | Eisai R&D Man Co Ltd | Hidtil ukendt pyridinderivat og pyrimidinderivat |
| ATE444294T1 (de) * | 2005-10-28 | 2009-10-15 | Irm Llc | Verbindungen und zusammensetzungen als proteinkinaseinhibitoren |
| 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. |
| US8003662B2 (en) | 2006-01-30 | 2011-08-23 | Array Biopharma, Inc. | Heterobicyclic thiophene compounds and methods of use |
| US7723330B2 (en) * | 2006-03-07 | 2010-05-25 | 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 |
| KR20090047391A (ko) | 2006-04-07 | 2009-05-12 | 데벨로겐 악틴게젤샤프트 | 약제학적 조성물을 위한 Ｍｎｋ1/Ｍｎｋ2 억제 활성을 갖는티에노피리미딘 |
| US20110053931A1 (en) * | 2006-06-08 | 2011-03-03 | John Gaudino | Quinoline compounds and methods of use |
| EP1889847A1 (en) | 2006-07-10 | 2008-02-20 | DeveloGen Aktiengesellschaft | Pyrrolopyrimidines for pharmaceutical compositions |
| WO2008021781A1 (en) | 2006-08-07 | 2008-02-21 | 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 |
| US20100016307A1 (en) * | 2006-10-27 | 2010-01-21 | Toshihiro Hamajima | Novel compounds |
| PL2497470T3 (pl) | 2006-11-22 | 2016-04-29 | Incyte Holdings Corp | Imidazotriazyny i imidazopirymidyny jako inhibitory kinazy |
| NZ590601A (en) | 2006-12-08 | 2011-09-30 | 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 |
| WO2009033084A1 (en) * | 2007-09-06 | 2009-03-12 | Array Biopharma Inc. | Pyrazolo-pyridines as tyrosine kinase inhibitors |
| JP2009132660A (ja) | 2007-11-30 | 2009-06-18 | Eisai R & D Management Co Ltd | 食道癌治療用組成物 |
| RU2498988C2 (ru) | 2008-03-05 | 2013-11-20 | Метилджин, Инк. | Ингибиторы активности протеинтирозинкиназы |
| JP6022158B2 (ja) | 2008-05-21 | 2016-11-09 | インサイト・ホールディングス・コーポレイションＩｎｃｙｔｅ Ｈｏｌｄｉｎｇｓ Ｃｏｒｐｏｒａｔｉｏｎ | ２−フルオロ−Ｎ−メチル−４−［７−（キノリン−６−イル−メチル）−イミダゾ［１，２−ｂ］［１，２，４］トリアジン−２−イル］ベンズアミドの塩及びそれを調製することに関する方法 |
| PT2384326E (pt) * | 2008-08-20 | 2014-06-09 | Zoetis Llc | Compostos de pirrolo[2,3-d]pirimidina |
| EP2331551B1 (en) | 2008-08-26 | 2016-06-29 | Evotec International GmbH | Thienopyrimidines for pharmaceutical compositions |
| WO2010045095A1 (en) * | 2008-10-14 | 2010-04-22 | Ning Xi | Compounds and methods of use |
| 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 |
| AU2010229147B2 (en) * | 2009-03-21 | 2012-07-05 | 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 | |
| JP5629324B2 (ja) * | 2009-10-15 | 2014-11-19 | ファイザー・インク | ピロロ［２，３−ｄ］ピリミジン化合物 |
| DE102009056886A1 (de) | 2009-12-03 | 2011-06-09 | Bayer Schering Pharma Aktiengesellschaft | cMet-Inhibitoren zur Behandlung der Endometriose |
| KR101870878B1 (ko) | 2010-02-03 | 2018-06-25 | 인사이트 홀딩스 코포레이션 | Ｃ―ＭＥＴ 억제제로서의 이미다조〔１，２―ｂ〕〔１，２，４〕트리아진 |
| AU2011219758A1 (en) | 2010-02-26 | 2012-08-16 | Boehringer Ingelheim International Gmbh | 4 - [cycloalkyloxy (hetero) arylamino] thieno [2, 3 - d] pyrimidines having Mnkl/ Mnk2 inhibiting activity for pharmaceutical compositions |
| BR112012021453A2 (pt) | 2010-02-26 | 2017-02-21 | Boehringer Ingelheim Int | tienopirimidina, sua composição farmacêutica e seu uso |
| UY33241A (es) | 2010-02-26 | 2011-09-30 | Boehringer Ingelheim Int | ?Tienopirimidinas que contienen heterocicloalquilo para composiciones farmacéuticas?. |
| 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 |
| WO2011146287A1 (en) | 2010-05-20 | 2011-11-24 | Takeda Pharmaceutical Company Limited | Pyrazolo[4,3-b]pyridine-7-amine inhibitors of alk5 |
| EP2586443B1 (en) | 2010-06-25 | 2016-03-16 | Eisai R&D Management Co., Ltd. | Antitumor agent using compounds having kinase inhibitory effect in combination |
| CN114209699A (zh) | 2010-07-16 | 2022-03-22 | 埃克塞里艾克西斯公司 | C-met调节剂药物组合物 |
| 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. |
| US9309322B2 (en) | 2010-11-12 | 2016-04-12 | Scott & White Healthcare (Swh) | Antibodies to tumor endothelial marker 8 |
| AR085155A1 (es) | 2011-02-10 | 2013-09-11 | Exelixis Inc | Procesos para preparar compuestos de quinolina y composiciones farmaceuticas que contienen dichos compuestos |
| US20120252840A1 (en) | 2011-04-04 | 2012-10-04 | Exelixis, Inc. | Method of Treating Cancer |
| TWI610918B (zh) | 2011-05-02 | 2018-01-11 | 艾克塞里克斯公司 | 治療癌症及骨癌疼痛之方法 |
| WO2013018929A1 (en) | 2011-08-04 | 2013-02-07 | Takeda Pharmaceutical Company Limited | Nitrogen-containing heterocyclic compound |
| KR20140069133A (ko) | 2011-09-22 | 2014-06-09 | 엑셀리시스, 인코포레이티드 | 골다공증의 치료방법 |
| WO2013042006A1 (en) | 2011-09-22 | 2013-03-28 | Pfizer Inc. | Pyrrolopyrimidine and purine derivatives |
| UA116876C2 (uk) * | 2011-10-20 | 2018-05-25 | Екселіксіс, Інк. | Спосіб одержання хінолінових похідних |
| US10799504B2 (en) | 2012-01-13 | 2020-10-13 | ACEA Therapeutics, Inc. | Heterocyclic compounds and uses as anticancer agents |
| US9464089B2 (en) | 2012-01-13 | 2016-10-11 | Acea Biosciences Inc. | Heterocyclic compounds 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 |
| US9034885B2 (en) | 2012-01-13 | 2015-05-19 | Acea Biosciences Inc. | EGFR modulators and uses thereof |
| US9815831B2 (en) | 2012-03-30 | 2017-11-14 | Rhizen Pharmaceuticals Sa | 3,5-disubstituted-3H-imidazo[4,5-B]pyridine and 3,5-disubstituted-3H-[1,2,3]triazolo[4,5-B] pyridine compounds as modulators of c-Met protein kinases |
| 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 |
| EP2917216B1 (en) | 2012-11-08 | 2017-10-18 | 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 |
| AU2013364953A1 (en) | 2012-12-21 | 2015-04-30 | Eisai R&D Management Co., Ltd. | Amorphous form of quinoline derivative, and method for producing same |
| GEP20196995B (en) | 2013-03-15 | 2019-07-25 | Inc Exelixis | Metabolites of n-(4-{[6,7-bis (methyloxy)quinolin-4-yl] oxy}phenyl)-n'-(4-fluorophenyl) cyclopropane-1,1-dicarboxamide |
| EP2981263B1 (en) | 2013-04-04 | 2022-06-29 | Exelixis, Inc. | Cabozantinib dosage form and use in the treatment of cancer |
| MX2015014046A (es) * | 2013-04-04 | 2016-05-16 | Exelixis Inc | Combinaciones de farmacos para tratar cancer. |
| CA2912219C (en) | 2013-05-14 | 2021-11-16 | Eisai R&D Management Co., Ltd. | Biomarkers for predicting and assessing responsiveness of endometrial cancer subjects to lenvatinib compounds |
| ES2761572T3 (es) | 2013-07-11 | 2020-05-20 | Acea Therapeutics Inc | Derivados de pirimidina como inhibidores de quinasa |
| WO2015123639A1 (en) | 2014-02-14 | 2015-08-20 | Exelixis, Inc. | Crystalline solid forms of n-{4-[(6,7-dimethoxyquinolin-4-yl)oxy]phenyl}-n'-(4-fluorophenyl) cyclopropane-1, 1-dicarboxamide, processes for making, and methods of use |
| WO2015148531A1 (en) | 2014-03-24 | 2015-10-01 | Genentech, Inc. | Cancer treatment with c-met antagonists and correlation of the latter with hgf expression |
| AP2016009464A0 (en) | 2014-04-25 | 2016-09-30 | Pfizer | Heteroaromatic compounds and their use as dopamine d1 ligands |
| WO2015162518A1 (en) | 2014-04-25 | 2015-10-29 | Pfizer Inc. | Heteroaromatic compounds and their use as dopamine d1 ligands |
| CN106715397B (zh) | 2014-07-31 | 2021-07-23 | 埃克塞里艾克西斯公司 | 制备氟-18标记的卡博替尼及其类似物的方法 |
| AU2015301097B2 (en) | 2014-08-05 | 2021-03-04 | Exelixis, Inc. | Drug combinations to treat multiple myeloma |
| EP4089076A1 (en) | 2014-08-28 | 2022-11-16 | Eisai R&D Management Co., Ltd. | High-purity quinoline derivative and method for manufacturing same |
| KR102763349B1 (ko) | 2015-02-25 | 2025-02-07 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 퀴놀린 유도체의 고미 억제 방법 |
| AU2015384801B2 (en) | 2015-03-04 | 2022-01-06 | Eisai R&D Management Co., Ltd. | Combination of a PD-1 antagonist and a VEGFR/FGFR/RET tyrosine kinase inhibitor for treating cancer |
| RU2729936C2 (ru) | 2015-06-16 | 2020-08-13 | Эйсай Ар Энд Ди Менеджмент Ко., Лтд. | Противораковое средство |
| CA2990752C (en) * | 2015-07-20 | 2020-03-10 | Betta Pharmaceuticals Co., Ltd | Crystalline form of fused pyridine derivative's maleate and uses thereof |
| EP3325473A4 (en) | 2015-07-22 | 2019-06-26 | The Royal Institution for the Advancement of Learning / McGill University | Compounds and uses thereof in the treatment of cancer and other medical disorders |
| SG11201801083UA (en) | 2015-08-20 | 2018-03-28 | Eisai R&D Man Co Ltd | Tumor therapeutic agent |
| KR20180067584A (ko) | 2015-10-09 | 2018-06-20 | 아세아 테라퓨틱스 인코포레이티드 | 피롤로피리미딘 키나아제 억제제의 약학적 염, 물리적 형태 및 조성물, 및 이들의 제조 방법 |
| 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 |
| CA3020749A1 (en) | 2016-04-15 | 2017-10-19 | 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 |
| KR102539920B1 (ko) | 2017-02-08 | 2023-06-05 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 종양-치료용 약제학적 조성물 |
| JP2020516682A (ja) | 2017-04-07 | 2020-06-11 | 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の薬学的な塩、物理的形態および組成物、ならびにその作製方法 |
| SG11201910100PA (en) | 2017-05-16 | 2019-11-28 | Eisai R&D Man Co Ltd | Treatment of hepatocellular carcinoma |
| WO2018228923A1 (en) | 2017-06-13 | 2018-12-20 | Bayer Pharma Aktiengesellschaft | Substituted pyrrolopyridine-derivatives as map4k1 modulators for the treatment of cancer diseases |
| US20200246347A1 (en) | 2017-06-13 | 2020-08-06 | Bayer Pharma Aktiengesellschaft | Substituted Pyrrolopyridine-Derivatives |
| WO2018228920A1 (en) | 2017-06-13 | 2018-12-20 | Bayer Pharma Aktiengesellschaft | Substituted pyrrolopyridine-derivatives |
| US11427578B1 (en) | 2017-07-18 | 2022-08-30 | Bayer Pharma Aktiengesellschaft | Substituted pyrrolopyridine-derivatives |
| AU2019215081B2 (en) | 2018-01-31 | 2024-07-25 | Deciphera Pharmaceuticals, Llc. | Combination therapy for the treatment of gastrointestinal stromal tumors |
| CN111886006B (zh) | 2018-01-31 | 2024-07-09 | 德西费拉制药有限责任公司 | 治疗肥大细胞增多症的组合疗法 |
| AU2019285066B2 (en) | 2018-06-15 | 2024-06-13 | Handa Pharmaceuticals, Inc. | Kinase inhibitor salts and compositions thereof |
| 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 |
| EP3894406A1 (en) | 2018-12-11 | 2021-10-20 | Bayer Aktiengesellschaft | Substituted pyrrolopyridine-derivatives |
| AR117472A1 (es) | 2018-12-21 | 2021-08-11 | Celgene Corp | Inhibidores de tienopiridina de 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 |
| CA3144228A1 (en) * | 2019-06-25 | 2020-12-30 | Sinopsee Therapeutics | Compounds for treatment of eye disorders |
| WO2021030405A1 (en) | 2019-08-12 | 2021-02-18 | Deciphera Pharmaceuticals, Llc | Ripretinib for treating gastrointestinal stromal tumors |
| MX2022001863A (es) | 2019-08-12 | 2022-05-30 | Deciphera Pharmaceuticals Llc | Metodos para tratar los tumores del estroma gastrointestinal. |
| CN119970649A (zh) | 2019-12-30 | 2025-05-13 | 德西费拉制药有限责任公司 | 非晶型激酶抑制剂制剂及其使用方法 |
| FI4084779T3 (fi) | 2019-12-30 | 2024-12-16 | Deciphera Pharmaceuticals Llc | 1-(4-bromi-5-(1-etyyli-7-(metyyliamino)-2-okso-1,2-dihydro-1,6-naftyridin-3-yyli)-2-fluorifenyyli)-3-fenyyliurean koostumuksia |
| 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 |
| EP4288437A1 (en) | 2021-02-05 | 2023-12-13 | Bayer Aktiengesellschaft | Map4k1 inhibitors |
| CN116836176A (zh) * | 2022-03-23 | 2023-10-03 | 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 |
| EP4622961A1 (en) * | 2022-11-25 | 2025-10-01 | Synthon B.V. | A process for preparation of cabozantinib or tivozanib |
| CN120417903A (zh) | 2023-01-31 | 2025-08-01 | 汉达癌症医药责任有限公司 | 改良的卡博替尼组合物及其使用方法 |
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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 |
| EP1243582A4 (en) * | 1999-12-24 | 2003-06-04 | Kirin Brewery | CHINOLINE AND CHINAZOLINE DERIVATIVES AND MEDICATIONS CONTAINING THEM |
| HU230302B1 (hu) * | 2000-10-20 | 2015-12-28 | Eisai R&D Management Co., Ltd. | Nitrogéntartalmú aromás származékok és ezeket tartalmazó gyógyászati készítmények |
| US7425564B2 (en) * | 2001-06-22 | 2008-09-16 | Kirin Beer Kabushiki Kaisha | Quinoline derivative and quinazoline derivative inhibiting self-phosphorylation of hepatocytus prolifertor 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 |
| EP1501829B1 (en) * | 2002-05-06 | 2010-11-24 | Vertex Pharmaceuticals Incorporated | Thiadiazoles or oxadiazoles and their use as inhibitors of jak protein kinase |
| GB0219746D0 (en) | 2002-08-23 | 2002-10-02 | Inst Of Ex Botany Ascr | Azapurine derivatives |
| CA2531485C (en) * | 2003-07-07 | 2013-03-26 | Merck Patent Gmbh | Malonamide derivatives |
| US7439246B2 (en) * | 2004-06-28 | 2008-10-21 | Bristol-Myers Squibb Company | Fused heterocyclic kinase inhibitors |
| US20050288290A1 (en) * | 2004-06-28 | 2005-12-29 | Borzilleri Robert M | Fused heterocyclic kinase inhibitors |
-
2005
- 2005-07-01 AU AU2005270068A patent/AU2005270068B2/en not_active Ceased
- 2005-07-01 US US11/571,140 patent/US7977345B2/en not_active Expired - Fee Related
- 2005-07-01 CA CA002572331A patent/CA2572331A1/en not_active Abandoned
- 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 WO PCT/US2005/023364 patent/WO2006014325A2/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| US7977345B2 (en) | 2011-07-12 |
| WO2006014325A2 (en) | 2006-02-09 |
| EP1773826A4 (en) | 2009-06-03 |
| WO2006014325A3 (en) | 2007-03-01 |
| JP2008505181A (ja) | 2008-02-21 |
| US20070179130A1 (en) | 2007-08-02 |
| AU2005270068B2 (en) | 2012-04-19 |
| EP1773826A2 (en) | 2007-04-18 |
| AU2005270068A1 (en) | 2006-02-09 |
| JP5368701B2 (ja) | 2013-12-18 |
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Legal Events
| Date | Code | Title | Description |
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| EEER | Examination request | ||
| FZDE | Discontinued |
Effective date: 20150702 |