PT2084162E - Triazoles bicíclicos como moduladores de proteína quinase - Google Patents
Triazoles bicíclicos como moduladores de proteína quinase Download PDFInfo
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- PT2084162E PT2084162E PT07844414T PT07844414T PT2084162E PT 2084162 E PT2084162 E PT 2084162E PT 07844414 T PT07844414 T PT 07844414T PT 07844414 T PT07844414 T PT 07844414T PT 2084162 E PT2084162 E PT 2084162E
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- methyl
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- mmol
- triazolo
- pyrazol
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Classifications
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- 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
- C07D487/02—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 two hetero rings
- C07D487/04—Ortho-condensed systems
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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
- A61K31/495—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
- A61K31/50—Pyridazines; Hydrogenated pyridazines
- A61K31/5025—Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring 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
- A61K31/53—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
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- 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
-
- 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
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
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| US86255206P | 2006-10-23 | 2006-10-23 | |
| US87030906P | 2006-12-15 | 2006-12-15 | |
| US91376607P | 2007-04-24 | 2007-04-24 | |
| US95284007P | 2007-07-30 | 2007-07-30 |
Publications (1)
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| PT2084162E true PT2084162E (pt) | 2012-10-09 |
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| PT07844414T PT2084162E (pt) | 2006-10-23 | 2007-10-18 | Triazoles bicíclicos como moduladores de proteína quinase |
Country Status (25)
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| US (1) | US8507489B2 (OSRAM) |
| EP (1) | EP2084162B1 (OSRAM) |
| JP (1) | JP5378222B2 (OSRAM) |
| KR (1) | KR20090071612A (OSRAM) |
| AR (1) | AR063520A1 (OSRAM) |
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| BR (1) | BRPI0717320A2 (OSRAM) |
| CA (1) | CA2667428A1 (OSRAM) |
| CO (1) | CO6190620A2 (OSRAM) |
| CR (1) | CR10803A (OSRAM) |
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| EA (1) | EA200970403A1 (OSRAM) |
| ES (1) | ES2393130T3 (OSRAM) |
| IL (1) | IL197958A0 (OSRAM) |
| MA (1) | MA30871B1 (OSRAM) |
| MX (1) | MX2009004059A (OSRAM) |
| NO (1) | NO20091618L (OSRAM) |
| NZ (1) | NZ575336A (OSRAM) |
| PE (1) | PE20080893A1 (OSRAM) |
| PL (1) | PL2084162T3 (OSRAM) |
| PT (1) | PT2084162E (OSRAM) |
| SV (1) | SV2009003235A (OSRAM) |
| TN (1) | TN2009000142A1 (OSRAM) |
| TW (1) | TW200835492A (OSRAM) |
| WO (1) | WO2008051808A2 (OSRAM) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| PA8792501A1 (es) * | 2007-08-09 | 2009-04-23 | Sanofi Aventis | Nuevos derivados de 6-triazolopiridacina-sulfanil benzotiazol y bencimidazol,su procedimiento de preparación,su aplicación como medicamentos,composiciones farmacéuticas y nueva utilización principalmente como inhibidores de met. |
| TWI365185B (en) | 2008-07-24 | 2012-06-01 | Lilly Co Eli | Amidophenoxyindazoles useful as inhibitors of c-met |
| UY32049A (es) | 2008-08-14 | 2010-03-26 | Takeda Pharmaceutical | Inhibidores de cmet |
| EP2165710A1 (en) * | 2008-09-19 | 2010-03-24 | Institut Curie | Tyrosine kinase receptor Tyro3 as a therapeutic target in the treatment of a bladder tumor |
| JP2012509342A (ja) | 2008-11-20 | 2012-04-19 | オーエスアイ・フアーマスーテイカルズ・インコーポレーテツド | 置換ピロロ［２，３−ｂ］−ピリジンおよび−ピラジン |
| FR2941950B1 (fr) * | 2009-02-06 | 2011-04-01 | Sanofi Aventis | Derives de 6-(6-o-substitue-triazolopyridazine-sulfanyl) benzothiazoles et benzimidazoles : preparation, application comme medicaments et utilisation comme inhibiteurs de met. |
| FR2941949B1 (fr) * | 2009-02-06 | 2011-04-01 | Sanofi Aventis | Derives de 6-(6-o-cycloalkyl ou 6-nh-cycloalkyl- triazolopyridazine-sulfanyl)benzothiazoles et benzimidazoles preparation, application comme medicaments et utilisation comme inhibiteurs de met. |
| FR2941951B1 (fr) * | 2009-02-06 | 2011-04-01 | Sanofi Aventis | Derives de 6-(6-nh-substitue-triazolopyridazine-sulfanyl) benzothiazoles et benzimidazoles : preparation, application comme medicaments et utilisation comme inhibiteurs de met. |
| FR2941952B1 (fr) * | 2009-02-06 | 2011-04-01 | Sanofi Aventis | Derives de 6-(6-substitue-triazolopyridazine-sulfanyl) 5-fluoro-benzothiazoles et 5-fluoro-benzimidazoles : preparation, application comme medicaments et utilisation comme inhibiteurs de met. |
| KR20120089643A (ko) | 2009-08-12 | 2012-08-13 | 노파르티스 아게 | 헤테로시클릭 히드라존 화합물, 및 암 및 염증을 치료하기 위한 그의 용도 |
| JP5775871B2 (ja) | 2009-08-20 | 2015-09-09 | ノバルティス アーゲー | ヘテロ環式オキシム化合物 |
| EP2719699B1 (en) | 2009-12-31 | 2015-07-08 | Hutchison Medipharma Limited | Certain triazolopyrazines, compositions thereof and methods of use therefor |
| AR081039A1 (es) | 2010-05-14 | 2012-05-30 | Osi Pharmaceuticals Llc | Inhibidores biciclicos fusionados de quinasa |
| US20130072495A1 (en) | 2010-05-14 | 2013-03-21 | OSI Pharmaceuticals, LLC | Fused bicyclic kinase inhibitors |
| AR085183A1 (es) | 2010-07-30 | 2013-09-18 | Lilly Co Eli | Compuesto 6-(1-metil-1h-pirazol-4-il)-3-(2-metil-2h-indazol-5-iltio)-[1,2,4]triazol[4,3-b]piridazina, composicion farmaceutica que lo comprende y uso para preparar un medicamento util para tratar cancer |
| UY33549A (es) * | 2010-08-10 | 2012-01-31 | Glaxo Group Ltd | Quinolil aminas como agentes inhibidores de las quinasas |
| WO2012042421A1 (en) | 2010-09-29 | 2012-04-05 | Pfizer Inc. | Method of treating abnormal cell growth |
| CN102532141A (zh) | 2010-12-08 | 2012-07-04 | 中国科学院上海药物研究所 | [1，2，4]三唑并[4，3-b][1，2，4]三嗪类化合物、其制备方法和用途 |
| US8765760B2 (en) | 2011-01-11 | 2014-07-01 | Sunovion Pharmaceuticals, Inc. | [1,2,4] triazol [1,5-a] pyrazines useful as inhibitors of phosphodiesterases |
| EP2673277A1 (en) * | 2011-02-10 | 2013-12-18 | Novartis AG | [1, 2, 4]triazolo [4, 3 -b]pyridazine compounds as inhibitors of the c-met tyrosine kinase |
| CN103459396B (zh) * | 2011-02-10 | 2015-08-19 | 诺瓦提斯公司 | 作为c-Met酪氨酸激酶抑制剂的[1,2,4]三唑并[4,3-b]哒嗪化合物 |
| JP2014513724A (ja) | 2011-05-16 | 2014-06-05 | オーエスアイ・ファーマシューティカルズ，エルエルシー | 融合二環キナーゼ阻害剤 |
| US9062045B2 (en) * | 2011-09-15 | 2015-06-23 | Novartis Ag | Triazolopyridine compounds |
| CN103958509B (zh) * | 2011-09-15 | 2015-12-23 | 诺华股份有限公司 | 作为酪氨酸激酶抑制剂的6-取代的3-(喹啉-6-基硫代)-[1,2,4]三唑并[4,3-a]吡啶化合物 |
| ES2894830T3 (es) | 2012-04-03 | 2022-02-16 | Novartis Ag | Productos combinados con inhibidores de tirosina·cinasa y su uso |
| WO2013151913A1 (en) | 2012-04-03 | 2013-10-10 | Novartis Ag | Tyrosine kinase inhibitor combinations and their use |
| CN103122000B (zh) * | 2012-09-03 | 2013-12-25 | 中美冠科生物技术（太仓）有限公司 | 用作抗肿瘤药物的高选择性的c-Met激酶抑制剂 |
| WO2014089904A1 (en) * | 2012-12-10 | 2014-06-19 | Abbvie Inc. | Triazinone compounds |
| WO2014164200A1 (en) | 2013-03-13 | 2014-10-09 | Avon Products, Inc | Tyrosinase inhibitors |
| WO2014140073A1 (en) * | 2013-03-13 | 2014-09-18 | F. Hoffmann-La Roche Ag | Process for making benzoxazepin compounds |
| US9364405B2 (en) | 2013-03-13 | 2016-06-14 | Avon Products, Inc. | Tyrosinase inhibitors |
| US20150152122A1 (en) * | 2013-03-13 | 2015-06-04 | Avon Products, Inc. | Tyrosinase inhibitors |
| WO2014174478A1 (en) | 2013-04-26 | 2014-10-30 | Novartis Ag | Pharmaceutical combinations of a pkc inhibitor and a c-met receptor tyrosine kinase inhibitor |
| US9512121B2 (en) | 2013-05-10 | 2016-12-06 | Jiangsu Hansoh Pharmaceutical Co., Ltd. | [1,2,4] triazol [4,3-A] pyridine derivative, preparation method therefor or medical application thereof |
| WO2017049711A1 (zh) | 2015-09-24 | 2017-03-30 | 上海海聚生物科技有限公司 | 喹啉类衍生物、其药物组合物、制备方法及应用 |
Family Cites Families (13)
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| US5604091A (en) | 1984-03-01 | 1997-02-18 | Microgenics Corporation | Methods for protein binding enzyme complementation |
| JPS60194443A (ja) * | 1984-03-16 | 1985-10-02 | Fuji Photo Film Co Ltd | ハロゲン化銀写真感光材料 |
| JPS62228086A (ja) * | 1985-12-23 | 1987-10-06 | Takeda Chem Ind Ltd | セフエム化合物 |
| EP0228061A3 (en) * | 1985-12-23 | 1988-12-14 | Takeda Chemical Industries, Ltd. | Cephem compounds |
| GB9918035D0 (en) | 1999-07-30 | 1999-09-29 | Novartis Ag | Organic compounds |
| AU2002251266A1 (en) | 2001-04-10 | 2002-10-28 | Merck Sharp And Dohme Limited | Inhibitors of akt activity |
| WO2002083139A1 (en) | 2001-04-10 | 2002-10-24 | Merck & Co., Inc. | Inhibitors of akt activity |
| US20030229453A1 (en) | 2002-04-09 | 2003-12-11 | Antonysamy Stephen Suresh | Crystals and structures of PAK4KD kinase PAK4KD |
| EP1575959B1 (en) * | 2002-12-18 | 2010-07-14 | Vertex Pharmaceuticals Incorporated | Compositions useful as inhibitors of protein kinases |
| US7122548B2 (en) * | 2003-07-02 | 2006-10-17 | Sugen, Inc. | Triazolotriazine compounds and uses thereof |
| CA2573573A1 (en) * | 2004-07-27 | 2006-02-09 | Sgx Pharmaceuticals, Inc. | Fused ring heterocycle kinase modulators |
| EA011725B1 (ru) | 2004-08-26 | 2009-04-28 | Пфайзер Инк. | Пиразолзамещённые аминогетероарильные соединения в качестве ингибиторов протеинкиназы |
| BRPI0519508A2 (pt) | 2004-12-27 | 2009-03-17 | Alcon Inc | análogos de aminopirazina para tratamento de glaucoma e outras doenças ou condições mediadas por rho cinase |
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Also Published As
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| TW200835492A (en) | 2008-09-01 |
| BRPI0717320A2 (pt) | 2013-10-22 |
| JP2010507578A (ja) | 2010-03-11 |
| SV2009003235A (es) | 2009-10-15 |
| CA2667428A1 (en) | 2008-05-02 |
| AU2007309149B2 (en) | 2012-09-06 |
| NO20091618L (no) | 2009-05-22 |
| TN2009000142A1 (en) | 2010-10-18 |
| MA30871B1 (fr) | 2009-11-02 |
| WO2008051808A3 (en) | 2008-07-24 |
| PL2084162T3 (pl) | 2013-01-31 |
| AR063520A1 (es) | 2009-01-28 |
| IL197958A0 (en) | 2009-12-24 |
| EA200970403A1 (ru) | 2009-10-30 |
| US8507489B2 (en) | 2013-08-13 |
| EP2084162B1 (en) | 2012-09-12 |
| KR20090071612A (ko) | 2009-07-01 |
| AU2007309149A1 (en) | 2008-05-02 |
| PE20080893A1 (es) | 2008-08-26 |
| DK2084162T3 (da) | 2012-10-01 |
| NZ575336A (en) | 2012-04-27 |
| CR10803A (es) | 2009-06-16 |
| US20090258855A1 (en) | 2009-10-15 |
| MX2009004059A (es) | 2009-04-27 |
| AU2007309149C1 (en) | 2013-04-04 |
| JP5378222B2 (ja) | 2013-12-25 |
| ES2393130T3 (es) | 2012-12-18 |
| WO2008051808A2 (en) | 2008-05-02 |
| CO6190620A2 (es) | 2010-08-19 |
| EP2084162A2 (en) | 2009-08-05 |
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