CA2656825C - Method of treatment and agents useful for same - Google Patents
Method of treatment and agents useful for same Download PDFInfo
- Publication number
- CA2656825C CA2656825C CA2656825A CA2656825A CA2656825C CA 2656825 C CA2656825 C CA 2656825C CA 2656825 A CA2656825 A CA 2656825A CA 2656825 A CA2656825 A CA 2656825A CA 2656825 C CA2656825 C CA 2656825C
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Classifications
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- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
-
- 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
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
-
- 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
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
Landscapes
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Engineering & Computer Science (AREA)
- Neurosurgery (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Quinoline Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US81577906P | 2006-06-22 | 2006-06-22 | |
| US60/815,779 | 2006-06-22 | ||
| PCT/AU2007/000876 WO2007147217A1 (en) | 2006-06-22 | 2007-06-22 | Method of treatment of glioma brain tumour |
Publications (2)
| Publication Number | Publication Date |
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| CA2656825A1 CA2656825A1 (en) | 2007-12-27 |
| CA2656825C true CA2656825C (en) | 2013-12-10 |
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| CA2656825A Expired - Fee Related CA2656825C (en) | 2006-06-22 | 2007-06-22 | Method of treatment and agents useful for same |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US8163760B2 (enExample) |
| EP (1) | EP2044026B1 (enExample) |
| JP (1) | JP5415942B2 (enExample) |
| CN (1) | CN101589026B (enExample) |
| AU (1) | AU2007262670B2 (enExample) |
| CA (1) | CA2656825C (enExample) |
| DK (1) | DK2044026T3 (enExample) |
| ES (1) | ES2474865T3 (enExample) |
| WO (1) | WO2007147217A1 (enExample) |
Families Citing this family (61)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2002950217A0 (en) | 2002-07-16 | 2002-09-12 | Prana Biotechnology Limited | 8- Hydroxy Quinoline Derivatives |
| ES2437997T3 (es) * | 2006-04-14 | 2014-01-15 | Prana Biotechnology Limited | Método de tratamiento de la degeneración macular relacionada con la edad (AMD) |
| WO2008079787A2 (en) * | 2006-12-20 | 2008-07-03 | Takeda San Diego, Inc. | Glucokinase activators |
| US9321730B2 (en) | 2007-08-21 | 2016-04-26 | The Hong Kong Polytechnic University | Method of making and administering quinoline derivatives as anti-cancer agents |
| US20110053873A1 (en) | 2008-02-01 | 2011-03-03 | Takeda Pharmaceutical Company Limited | Hsp90 inhibitors |
| GB0806794D0 (en) * | 2008-04-15 | 2008-05-14 | Ludwig Inst Cancer Res | Therapeutic compounds |
| CA2737219C (en) * | 2008-08-11 | 2017-02-28 | Tracy Keller | Halofuginone analogs for inhibition of trna synthetases and uses thereof |
| ES2634492T3 (es) * | 2008-12-24 | 2017-09-28 | Prana Biotechnology Ltd | Compuestos de quinazolinona |
| US10253020B2 (en) | 2009-06-12 | 2019-04-09 | Abivax | Compounds for preventing, inhibiting, or treating cancer, AIDS and/or premature aging |
| CN102603628B (zh) * | 2010-12-22 | 2016-08-17 | 香港理工大学 | 作为抗癌试剂的喹啉衍生物 |
| WO2012088266A2 (en) | 2010-12-22 | 2012-06-28 | Incyte Corporation | Substituted imidazopyridazines and benzimidazoles as inhibitors of fgfr3 |
| EP2565186A1 (en) | 2011-09-02 | 2013-03-06 | Hybrigenics S.A. | Selective and reversible inhibitors of ubiquitin specific protease 7 |
| FR2984317B1 (fr) * | 2011-12-20 | 2015-02-27 | Univ Rennes | Composes chelateurs de metal presentant au moins une chaine polyaminee. |
| AU2013207796B2 (en) | 2012-01-13 | 2017-04-27 | President And Fellows Of Harvard College | Halofuginol derivatives and their use in cosmetic and pharmaceutical compositions |
| HUE042374T2 (hu) | 2012-06-13 | 2019-06-28 | Incyte Holdings Corp | Szubsztituált triciklusos vegyületek mint FGFR inhibitorok |
| US9388185B2 (en) | 2012-08-10 | 2016-07-12 | Incyte Holdings Corporation | Substituted pyrrolo[2,3-b]pyrazines as FGFR inhibitors |
| US9266892B2 (en) | 2012-12-19 | 2016-02-23 | Incyte Holdings Corporation | Fused pyrazoles as FGFR inhibitors |
| CA2886139A1 (en) | 2012-12-27 | 2014-07-03 | F. Hoffmann-La Roche Ag | Comt inhibitors |
| EP2757161A1 (en) | 2013-01-17 | 2014-07-23 | Splicos | miRNA-124 as a biomarker of viral infection |
| KR102469849B1 (ko) | 2013-04-19 | 2022-11-23 | 인사이트 홀딩스 코포레이션 | Fgfr 저해제로서 이환식 헤테로사이클 |
| CA2927830A1 (en) | 2013-10-23 | 2015-04-30 | Chugai Seiyaku Kabushiki Kaisha | Quinazolinone and isoquinolinone derivative |
| EP2974729A1 (en) | 2014-07-17 | 2016-01-20 | Abivax | Quinoline derivatives for use in the treatment of inflammatory diseases |
| US10851105B2 (en) | 2014-10-22 | 2020-12-01 | Incyte Corporation | Bicyclic heterocycles as FGFR4 inhibitors |
| EA031505B1 (ru) * | 2014-12-02 | 2019-01-31 | Прана Байотекнолоджи Лимитед | СОЕДИНЕНИЯ 4Н-ПИРИДО[1,2-а]ПИРИМИДИН-4-ОНА |
| WO2016134294A1 (en) | 2015-02-20 | 2016-08-25 | Incyte Corporation | Bicyclic heterocycles as fgfr4 inhibitors |
| AU2016219822B2 (en) | 2015-02-20 | 2020-07-09 | Incyte Holdings Corporation | Bicyclic heterocycles as FGFR inhibitors |
| MA41551A (fr) | 2015-02-20 | 2017-12-26 | Incyte Corp | Hétérocycles bicycliques utilisés en tant qu'inhibiteurs de fgfr4 |
| TW201815787A (zh) | 2016-09-23 | 2018-05-01 | 美商基利科學股份有限公司 | 磷脂醯肌醇3-激酶抑制劑 |
| TW201825465A (zh) | 2016-09-23 | 2018-07-16 | 美商基利科學股份有限公司 | 磷脂醯肌醇3-激酶抑制劑 |
| TW201813963A (zh) | 2016-09-23 | 2018-04-16 | 美商基利科學股份有限公司 | 磷脂醯肌醇3-激酶抑制劑 |
| AR111960A1 (es) | 2017-05-26 | 2019-09-04 | Incyte Corp | Formas cristalinas de un inhibidor de fgfr y procesos para su preparación |
| WO2019067503A1 (en) * | 2017-09-26 | 2019-04-04 | Dana-Farber Cancer Institute, Inc. | NEW USP7 INHIBITORS FOR THE TREATMENT OF MULTIPLE MYELOMA |
| EP3788046B1 (en) | 2018-05-04 | 2025-12-10 | Incyte Corporation | Salts of an fgfr inhibitor |
| EP4309737A3 (en) | 2018-05-04 | 2024-03-27 | Incyte Corporation | Solid forms of an fgfr inhibitor and processes for preparing the same |
| US11708353B2 (en) | 2018-06-08 | 2023-07-25 | The General Hospital Corporation | Inhibitors of prolyl-tRNA-synthetase |
| EP3669873A1 (en) | 2018-12-20 | 2020-06-24 | Abivax | Quinoline derivatives for use ine the traeatment of inflammation diseases |
| CN111471012B (zh) * | 2019-01-23 | 2023-04-25 | 鲁南制药集团股份有限公司 | 一种蜈蚣喹啉类化合物、制备方法及其应用 |
| US11628162B2 (en) | 2019-03-08 | 2023-04-18 | Incyte Corporation | Methods of treating cancer with an FGFR inhibitor |
| US11591329B2 (en) | 2019-07-09 | 2023-02-28 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
| CN110240590B (zh) * | 2019-07-16 | 2025-09-19 | 广州新民培林医药科技有限公司 | 一类嘧啶喹啉衍生物及其制备方法和应用 |
| US12122767B2 (en) | 2019-10-01 | 2024-10-22 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
| WO2021076602A1 (en) | 2019-10-14 | 2021-04-22 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
| WO2021076728A1 (en) | 2019-10-16 | 2021-04-22 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
| MX2022006700A (es) | 2019-12-02 | 2022-09-02 | Storm Therapeutics Ltd | Compuestos poliheterociclicos como inhibidores de mettl3. |
| KR20220131900A (ko) | 2019-12-04 | 2022-09-29 | 인사이트 코포레이션 | Fgfr 억제제의 유도체 |
| JP7720840B2 (ja) | 2019-12-04 | 2025-08-08 | インサイト・コーポレイション | Ｆｇｆｒ阻害剤としての三環式複素環 |
| US12012409B2 (en) | 2020-01-15 | 2024-06-18 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
| WO2021257863A1 (en) | 2020-06-19 | 2021-12-23 | Incyte Corporation | Pyrrolotriazine compounds as jak2 v617f inhibitors |
| US11691971B2 (en) | 2020-06-19 | 2023-07-04 | Incyte Corporation | Naphthyridinone compounds as JAK2 V617F inhibitors |
| US11767323B2 (en) | 2020-07-02 | 2023-09-26 | Incyte Corporation | Tricyclic pyridone compounds as JAK2 V617F inhibitors |
| IL299612A (en) | 2020-07-02 | 2023-03-01 | Incyte Corp | Tricyclic urea compounds as JAK2 V617F inhibitors |
| US11661422B2 (en) | 2020-08-27 | 2023-05-30 | Incyte Corporation | Tricyclic urea compounds as JAK2 V617F inhibitors |
| WO2022140231A1 (en) | 2020-12-21 | 2022-06-30 | Incyte Corporation | Deazaguaine compounds as jak2 v617f inhibitors |
| US11958861B2 (en) | 2021-02-25 | 2024-04-16 | Incyte Corporation | Spirocyclic lactams as JAK2 V617F inhibitors |
| CA3215903A1 (en) | 2021-04-12 | 2022-10-20 | Incyte Corporation | Combination therapy comprising an fgfr inhibitor and a nectin-4 targeting agent |
| CN113214249B (zh) * | 2021-04-23 | 2023-09-19 | 成都大学 | 吡啶并[1,2-a]嘧啶-4-硫酮化合物的合成方法 |
| EP4352059A1 (en) | 2021-06-09 | 2024-04-17 | Incyte Corporation | Tricyclic heterocycles as fgfr inhibitors |
| WO2022261159A1 (en) | 2021-06-09 | 2022-12-15 | Incyte Corporation | Tricyclic heterocycles as fgfr inhibitors |
| AU2022380979A1 (en) | 2021-11-02 | 2024-06-06 | Flare Therapeutics Inc. | Pparg inverse agonists and uses thereof |
| EP4493558A1 (en) | 2022-03-17 | 2025-01-22 | Incyte Corporation | Tricyclic urea compounds as jak2 v617f inhibitors |
| CN116410132B (zh) * | 2023-02-23 | 2024-07-09 | 广东工业大学 | 一种8-羟基喹啉类化合物及其制备方法和在制备抗肿瘤药物上的应用 |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2368047A1 (en) | 1999-03-24 | 2000-09-28 | Anormed Inc. | Chemokine receptor binding heterocyclic compounds |
| CN1891693A (zh) * | 2000-01-24 | 2007-01-10 | 基纳西亚股份有限公司 | 用于治疗的吗啉代基取代的化合物 |
| AU2002230056A1 (en) * | 2001-01-29 | 2002-08-12 | Insight Strategy And Marketing Ltd | Indole derivatives and their uses as heparanase inhibitors |
| CN1638776A (zh) * | 2001-06-08 | 2005-07-13 | 西托维亚公司 | 取代的3－芳基－5－芳基－[1,2,4]－噁二唑和类似物 |
| MXPA04007083A (es) | 2002-02-20 | 2004-10-29 | Upjohn Co | Compuestos azabiciclicos para el tratamiento de enfermedades. |
| EP1549614A4 (en) * | 2002-10-03 | 2008-04-16 | Targegen Inc | VASCULATORY AGENTS AND METHODS FOR THEIR APPLICATION |
| EP1558585B1 (en) * | 2002-10-04 | 2013-09-25 | Prana Biotechnology Limited | Neurologically-active compounds |
| WO2005063213A1 (en) | 2003-12-19 | 2005-07-14 | Biodelivery Sciences International, Inc. | Rigid liposomal cochleate and methods of use and manufacture |
| WO2006031806A2 (en) | 2004-09-10 | 2006-03-23 | Atherogenics, Inc. | 2-thiopyrimidinones as therapeutic agents |
| KR20080080584A (ko) | 2005-11-30 | 2008-09-04 | 버텍스 파마슈티칼스 인코포레이티드 | ｃ-Ｍｅｔ의 억제제 및 이의 용도 |
| DE102005059479A1 (de) * | 2005-12-13 | 2007-06-14 | Merck Patent Gmbh | Hydroxychinolinderivate |
| ES2437997T3 (es) * | 2006-04-14 | 2014-01-15 | Prana Biotechnology Limited | Método de tratamiento de la degeneración macular relacionada con la edad (AMD) |
-
2007
- 2007-06-22 JP JP2009515675A patent/JP5415942B2/ja not_active Expired - Fee Related
- 2007-06-22 EP EP07719115.3A patent/EP2044026B1/en not_active Not-in-force
- 2007-06-22 DK DK07719115.3T patent/DK2044026T3/da active
- 2007-06-22 ES ES07719115.3T patent/ES2474865T3/es active Active
- 2007-06-22 US US12/306,202 patent/US8163760B2/en not_active Expired - Fee Related
- 2007-06-22 AU AU2007262670A patent/AU2007262670B2/en not_active Ceased
- 2007-06-22 CA CA2656825A patent/CA2656825C/en not_active Expired - Fee Related
- 2007-06-22 WO PCT/AU2007/000876 patent/WO2007147217A1/en not_active Ceased
- 2007-06-22 CN CN2007800311672A patent/CN101589026B/zh not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| EP2044026B1 (en) | 2014-03-26 |
| JP5415942B2 (ja) | 2014-02-12 |
| AU2007262670A1 (en) | 2007-12-27 |
| CA2656825A1 (en) | 2007-12-27 |
| EP2044026A4 (en) | 2009-08-05 |
| JP2009541223A (ja) | 2009-11-26 |
| WO2007147217A1 (en) | 2007-12-27 |
| AU2007262670B2 (en) | 2012-12-20 |
| CN101589026A (zh) | 2009-11-25 |
| ES2474865T3 (es) | 2014-07-09 |
| DK2044026T3 (da) | 2014-06-30 |
| CN101589026B (zh) | 2013-10-16 |
| EP2044026A1 (en) | 2009-04-08 |
| AU2007262670A2 (en) | 2009-03-26 |
| US20100069393A1 (en) | 2010-03-18 |
| US8163760B2 (en) | 2012-04-24 |
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