CA2667453A1 - Triazolo-pyridazine protein kinase modulators - Google Patents
Triazolo-pyridazine protein kinase modulators Download PDFInfo
- Publication number
- CA2667453A1 CA2667453A1 CA002667453A CA2667453A CA2667453A1 CA 2667453 A1 CA2667453 A1 CA 2667453A1 CA 002667453 A CA002667453 A CA 002667453A CA 2667453 A CA2667453 A CA 2667453A CA 2667453 A1 CA2667453 A1 CA 2667453A1
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- CA
- Canada
- Prior art keywords
- substituted
- unsubstituted
- alkyl
- pyridinyl
- halogen
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
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- 102000001253 Protein Kinase Human genes 0.000 title claims abstract description 52
- 108060006633 protein kinase Proteins 0.000 title claims abstract description 52
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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
-
- 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
- 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
-
- 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
-
- 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)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (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)
Applications Claiming Priority (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US86255206P | 2006-10-23 | 2006-10-23 | |
| US60/862,552 | 2006-10-23 | ||
| US87138406P | 2006-12-21 | 2006-12-21 | |
| US60/871,384 | 2006-12-21 | ||
| US91375207P | 2007-04-24 | 2007-04-24 | |
| US60/913,752 | 2007-04-24 | ||
| US95283307P | 2007-07-30 | 2007-07-30 | |
| US60/952,833 | 2007-07-30 | ||
| PCT/US2007/081832 WO2008051805A2 (en) | 2006-10-23 | 2007-10-18 | Triazolo-pyridazine protein kinase modulators |
Publications (1)
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| CA2667453A1 true CA2667453A1 (en) | 2008-05-02 |
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| CA002667453A Abandoned CA2667453A1 (en) | 2006-10-23 | 2007-10-18 | Triazolo-pyridazine protein kinase modulators |
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| EP (1) | EP2081937B1 (OSRAM) |
| JP (1) | JP2010507577A (OSRAM) |
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| AU (1) | AU2007309237B2 (OSRAM) |
| BR (1) | BRPI0717317A2 (OSRAM) |
| CA (1) | CA2667453A1 (OSRAM) |
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| EA (1) | EA016527B1 (OSRAM) |
| ES (1) | ES2393132T3 (OSRAM) |
| MX (1) | MX2009004060A (OSRAM) |
| PE (1) | PE20081256A1 (OSRAM) |
| PL (1) | PL2081937T3 (OSRAM) |
| PT (1) | PT2081937E (OSRAM) |
| TW (1) | TW200833692A (OSRAM) |
| WO (1) | WO2008051805A2 (OSRAM) |
Families Citing this family (69)
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| US10022352B2 (en) | 2006-04-07 | 2018-07-17 | Vertex Pharmaceuticals Incorporated | Modulators of ATP-binding cassette transporters |
| USRE50453E1 (en) | 2006-04-07 | 2025-06-10 | Vertex Pharmaceuticals Incorporated | Indole derivatives as CFTR modulators |
| US7645789B2 (en) | 2006-04-07 | 2010-01-12 | Vertex Pharmaceuticals Incorporated | Indole derivatives as CFTR modulators |
| PT2674428T (pt) | 2006-04-07 | 2016-07-14 | Vertex Pharma | Modeladores de transportadores de cassetes de ligação de atp |
| US8217177B2 (en) * | 2006-07-14 | 2012-07-10 | Amgen Inc. | Fused heterocyclic derivatives and methods of use |
| US8198448B2 (en) | 2006-07-14 | 2012-06-12 | Amgen Inc. | Fused heterocyclic derivatives and methods of use |
| PE20121506A1 (es) | 2006-07-14 | 2012-11-26 | Amgen Inc | Compuestos triazolopiridinas como inhibidores de c-met |
| JP2010500365A (ja) | 2006-08-07 | 2010-01-07 | インサイト・コーポレイション | キナーゼ阻害剤としてのトリアゾロトリアジン |
| US8563573B2 (en) | 2007-11-02 | 2013-10-22 | Vertex Pharmaceuticals Incorporated | Azaindole derivatives as CFTR modulators |
| BRPI0719333A2 (pt) | 2006-11-22 | 2014-02-04 | Incyte Corp | Midazotriazinas e imidazopirimidinas como inbidores de cinase |
| WO2009106577A1 (en) | 2008-02-28 | 2009-09-03 | Novartis Ag | Imidazo [1,2-b] pyridazine derivatives for the treatment of c-met tyrosine kinase mediated disease |
| BRPI0912882A2 (pt) | 2008-05-21 | 2017-05-16 | Incyte Corp | sais de 2-flúor-n-metil-4-[7-(quinolin-6-il-metil)-imidazo[1,2-b][1,2,4]triazin-2-il]benzamida e processos relacionados à preparação dos mesmos |
| DE102008028905A1 (de) | 2008-06-18 | 2009-12-24 | Merck Patent Gmbh | 3-(3-Pyrimidin-2-yl-benzyl)-[1,2,4]triazolo[4,3-b]pyridazinderivate |
| DE102008037790A1 (de) | 2008-08-14 | 2010-02-18 | Merck Patent Gmbh | Bicyclische Triazolderivate |
| DE102008038221A1 (de) | 2008-08-18 | 2010-02-25 | Merck Patent Gmbh | 7-Azaindolderivate |
| DE102008038222A1 (de) | 2008-08-18 | 2010-02-25 | Merck Patent Gmbh | Indazol-5-carbonsäurehydrazid-derivate |
| DE102008038220A1 (de) | 2008-08-18 | 2010-02-25 | Merck Patent Gmbh | Oxadiazolderivate |
| US8592448B2 (en) | 2008-11-20 | 2013-11-26 | OSI Pharmaceuticals, LLC | Substituted pyrrolo[2,3-b]-pyridines and -pyrazines |
| WO2010068292A1 (en) | 2008-12-12 | 2010-06-17 | Ariad Pharmaceuticals, Inc. | Azaindole derivatives as kinase inhibitors |
| DE102008063667A1 (de) | 2008-12-18 | 2010-07-01 | Merck Patent Gmbh | 3-(3-Pyrimidin-2-yl-benzyl)-°[1,2,4]triazolo[4,3-b]pyrimidin-derivate |
| DE102008062825A1 (de) | 2008-12-23 | 2010-06-24 | Merck Patent Gmbh | 3-(3-Pyrimidin-2-yl-benzyl)-[1,2,4]triazolo [4,3-b]pyridazin-derivate |
| KR20110113755A (ko) * | 2009-02-10 | 2011-10-18 | 아스트라제네카 아베 | 트리아졸로 〔4,3-ｂ〕 피리다진 유도체 및 전립샘암에 대한 이의 용도 |
| JP2012519731A (ja) * | 2009-03-09 | 2012-08-30 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | ニコチン受容体およびｇａｂａａ受容体のアロステリックモジュレーターとしての置換複素環およびそれらの使用 |
| US8389526B2 (en) | 2009-08-07 | 2013-03-05 | Novartis Ag | 3-heteroarylmethyl-imidazo[1,2-b]pyridazin-6-yl derivatives |
| EA201200260A1 (ru) | 2009-08-12 | 2012-09-28 | Новартис Аг | Гетероциклические гидразоны и их применение для лечения рака и воспаления |
| IN2012DN01453A (OSRAM) | 2009-08-20 | 2015-06-05 | Novartis Ag | |
| PL2719699T3 (pl) * | 2009-12-31 | 2016-01-29 | Hutchison Medipharma Ltd | Pewne triazolopirazyny, ich kompozycje i sposoby ich stosowania |
| MX2012008898A (es) | 2010-02-03 | 2012-11-06 | Incyte Corp | Imidazo - [1, 2 - b] [1, 2, 4] triazinas como inhibidores de c - met. |
| US8802868B2 (en) | 2010-03-25 | 2014-08-12 | Vertex Pharmaceuticals Incorporated | Solid forms of (R)-1(2,2-difluorobenzo[D][1,3]dioxo1-5-yl)-N-(1-(2,3-dihydroxypropyl-6-fluoro-2-(1-hydroxy-2-methylpropan2-yl)-1H-Indol-5-yl)-Cyclopropanecarboxamide |
| CA2797118C (en) * | 2010-04-22 | 2021-03-30 | Vertex Pharmaceuticals Incorporated | Process of producing cycloalkylcarboxamido-indole compounds |
| JP2013526570A (ja) | 2010-05-14 | 2013-06-24 | オーエスアイ・ファーマシューティカルズ，エルエルシー | 縮合二環式キナーゼ阻害剤 |
| AR081039A1 (es) | 2010-05-14 | 2012-05-30 | Osi Pharmaceuticals Llc | Inhibidores biciclicos fusionados de quinasa |
| EP2571878B1 (en) | 2010-05-17 | 2018-10-17 | 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 |
| US10414760B2 (en) | 2016-11-29 | 2019-09-17 | Angion Biomedica Corp. | Cytochrome P450 inhibitors and uses thereof |
| AU2011261586B2 (en) * | 2010-06-01 | 2015-08-27 | Angion Biomedica Corp. | Cytochrome P450 inhibitors and uses thereof |
| 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 |
| 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 |
| US20140088114A1 (en) | 2011-05-16 | 2014-03-27 | OSI Pharmaceuticals ,LLC | Fused bicyclic kinase inhibitors |
| EP2755976B1 (en) | 2011-09-15 | 2018-07-18 | Novartis AG | 6-substituted 3-(quinolin-6-ylthio)-[1,2,4]triazolo[4,3-a]pyridines as c-met tyrosine kinase inhibitors |
| MX356683B (es) | 2011-09-27 | 2018-06-08 | Genfit | Derivados de triazolpiridazinas 6-sustituidas como agonistas rev-erb. |
| KR101869534B1 (ko) * | 2012-03-05 | 2018-06-20 | 한국화학연구원 | 신규한 트리아졸로 피리다진 유도체 및 그의 용도 |
| KR20140144726A (ko) | 2012-03-30 | 2014-12-19 | 리젠 파마슈티컬스 소시에떼 아노님 | C-met 단백질 키나제의 조절제로서의 신규한 3,5-디치환-3h-이미다조[4,5-b]피리딘 및 3,5- 디치환 -3h-[1,2,3]트리아졸로[4,5-b] 피리딘 화합물 |
| AU2013290444B2 (en) | 2012-07-16 | 2018-04-26 | Vertex Pharmaceuticals Incorporated | Pharmaceutical compositions of (R)-1-(2,2-diflurorbenzo[d][1,3]dioxol-5-yl)-N-(1-(2,3-dihydroxypropyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1H-indol-5-yl) cyclopropanecarboxamide and administration thereof |
| 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 |
| ME02794B (me) | 2012-10-16 | 2018-01-20 | Janssen Pharmaceutica Nv | Metilen vezani hinolinil modulatori ror-gama-t |
| JP6250686B2 (ja) | 2012-10-16 | 2017-12-20 | ヤンセン ファーマシューティカ エヌ．ベー． | Ｒｏｒγｔのヘテロアリール結合させたキノリニルモジュレータ |
| US9309222B2 (en) | 2012-10-16 | 2016-04-12 | Janssen Pharmaceutica Nv | Phenyl linked quinolinyl modulators of RORγt |
| WO2014133526A1 (en) | 2013-02-28 | 2014-09-04 | Empire Technology Development Llc | Colored pigment particles for electrophoretic displays |
| EP3404032B1 (en) | 2013-03-13 | 2025-07-02 | F. Hoffmann-La Roche AG | Process for making benzoxazepin compounds |
| US20140303121A1 (en) | 2013-03-15 | 2014-10-09 | Plexxikon Inc. | Heterocyclic compounds and uses thereof |
| DK2970265T3 (en) * | 2013-03-15 | 2018-10-01 | Plexxikon Inc | HETEROCYCLIC COMPOUNDS AND APPLICATIONS THEREOF |
| ES2770727T3 (es) | 2013-10-15 | 2020-07-02 | Janssen Pharmaceutica Nv | Moduladores de quinilonila enlazados a alquilo de ROR(gamma)t |
| US10555941B2 (en) | 2013-10-15 | 2020-02-11 | Janssen Pharmaceutica Nv | Alkyl linked quinolinyl modulators of RORγt |
| US9328095B2 (en) | 2013-10-15 | 2016-05-03 | Janssen Pharmaceutica Nv | Heteroaryl linked quinolinyl modulators of RORgammat |
| ES2742843T3 (es) | 2013-10-15 | 2020-02-17 | Janssen Pharmaceutica Nv | Moduladores de quinolinilo de ROR(gamma)t |
| US9403816B2 (en) | 2013-10-15 | 2016-08-02 | Janssen Pharmaceutica Nv | Phenyl linked quinolinyl modulators of RORγt |
| US9221804B2 (en) | 2013-10-15 | 2015-12-29 | Janssen Pharmaceutica Nv | Secondary alcohol quinolinyl modulators of RORγt |
| US9284308B2 (en) | 2013-10-15 | 2016-03-15 | Janssen Pharmaceutica Nv | Methylene linked quinolinyl modulators of RORγt |
| GB201321745D0 (en) * | 2013-12-09 | 2014-01-22 | Ucb Pharma Sa | Therapeutic agents |
| WO2015134854A2 (en) * | 2014-03-06 | 2015-09-11 | Oyagen, Inc. | Small molecule vif dimerization antagonists as anti-hiv agents and for use as hiv/aids therapeutics |
| CA2944140C (en) | 2014-04-15 | 2022-10-04 | Vertex Pharmaceuticals Incorporated | Pharmaceutical compositions for the treatment of cystic fibrosis transmembrane conductance regulator mediated diseases |
| CA2957785C (en) | 2014-08-11 | 2023-01-03 | Angion Biomedica Corporation | Cytochrome p450 inhibitors and uses thereof |
| WO2016109492A1 (en) | 2014-12-31 | 2016-07-07 | Angion Biomedica Corp | Methods and agents for treating disease |
| CA2980460A1 (en) | 2015-04-13 | 2016-10-20 | Five Prime Therapeutics, Inc. | Combination therapy for cancer |
| RU2748884C2 (ru) | 2015-07-20 | 2021-06-01 | Джензим Корпорейшн | Ингибиторы рецептора колониестимулирующего фактора-1 (csf-1r) |
| EP3694855A1 (en) | 2017-10-13 | 2020-08-19 | Plexxikon Inc. | Solid forms of a compound for modulating kinases |
| GB201905721D0 (en) | 2019-04-24 | 2019-06-05 | Univ Dundee | Compounds |
| CN113861198B (zh) * | 2020-06-30 | 2024-08-02 | 上海医药集团股份有限公司 | 咪唑并[4,5-b]吡嗪类化合物、其制备方法及应用 |
| JP2024500919A (ja) | 2020-12-23 | 2024-01-10 | ジェンザイム・コーポレーション | 重水素化コロニー刺激因子－１受容体（ｃｓｆ－１ｒ）阻害剤 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2002083139A1 (en) * | 2001-04-10 | 2002-10-24 | Merck & Co., Inc. | Inhibitors of akt activity |
| AU2002251266A1 (en) | 2001-04-10 | 2002-10-28 | Merck Sharp And Dohme Limited | Inhibitors of akt activity |
| US7337831B2 (en) * | 2001-08-10 | 2008-03-04 | Yokohama Tlo Company Ltd. | Heat transfer device |
| ME02736B (me) * | 2005-12-21 | 2017-10-20 | Janssen Pharmaceutica Nv | Triazolopiridazini kao modulatori tirozin kinaze |
| EP2032578A2 (en) * | 2006-05-30 | 2009-03-11 | Pfizer Products Incorporated | Triazolopyridazine derivatives |
| PE20121506A1 (es) * | 2006-07-14 | 2012-11-26 | Amgen Inc | Compuestos triazolopiridinas como inhibidores de c-met |
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- 2007-10-18 AU AU2007309237A patent/AU2007309237B2/en not_active Ceased
- 2007-10-18 BR BRPI0717317-2A2A patent/BRPI0717317A2/pt not_active IP Right Cessation
- 2007-10-18 CA CA002667453A patent/CA2667453A1/en not_active Abandoned
- 2007-10-18 MX MX2009004060A patent/MX2009004060A/es not_active Application Discontinuation
- 2007-10-18 EA EA200970402A patent/EA016527B1/ru not_active IP Right Cessation
- 2007-10-18 KR KR1020097007986A patent/KR101083177B1/ko not_active Expired - Fee Related
- 2007-10-18 US US12/442,987 patent/US8071581B2/en not_active Expired - Fee Related
- 2007-10-18 DK DK07854193.5T patent/DK2081937T3/da active
- 2007-10-18 PT PT07854193T patent/PT2081937E/pt unknown
- 2007-10-18 JP JP2009533536A patent/JP2010507577A/ja not_active Withdrawn
- 2007-10-18 EP EP07854193A patent/EP2081937B1/en active Active
- 2007-10-18 WO PCT/US2007/081832 patent/WO2008051805A2/en not_active Ceased
- 2007-10-18 PL PL07854193T patent/PL2081937T3/pl unknown
- 2007-10-22 TW TW096139481A patent/TW200833692A/zh unknown
- 2007-10-23 PE PE2007001436A patent/PE20081256A1/es not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| KR101083177B1 (ko) | 2011-11-11 |
| EA016527B1 (ru) | 2012-05-30 |
| EP2081937A2 (en) | 2009-07-29 |
| AU2007309237A1 (en) | 2008-05-02 |
| TW200833692A (en) | 2008-08-16 |
| WO2008051805A3 (en) | 2008-07-10 |
| US8071581B2 (en) | 2011-12-06 |
| KR20090069303A (ko) | 2009-06-30 |
| ES2393132T3 (es) | 2012-12-18 |
| BRPI0717317A2 (pt) | 2013-10-22 |
| WO2008051805A2 (en) | 2008-05-02 |
| DK2081937T3 (da) | 2012-10-01 |
| EP2081937B1 (en) | 2012-09-12 |
| US20100120739A1 (en) | 2010-05-13 |
| EA200970402A1 (ru) | 2009-10-30 |
| JP2010507577A (ja) | 2010-03-11 |
| MX2009004060A (es) | 2009-06-19 |
| AU2007309237B2 (en) | 2012-03-22 |
| PE20081256A1 (es) | 2008-10-13 |
| PL2081937T3 (pl) | 2013-01-31 |
| PT2081937E (pt) | 2012-10-15 |
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