ES2393132T3 - Moduoladores de proteína quinasa de triazolopiridazina - Google Patents
Moduoladores de proteína quinasa de triazolopiridazina Download PDFInfo
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- ES2393132T3 ES2393132T3 ES07854193T ES07854193T ES2393132T3 ES 2393132 T3 ES2393132 T3 ES 2393132T3 ES 07854193 T ES07854193 T ES 07854193T ES 07854193 T ES07854193 T ES 07854193T ES 2393132 T3 ES2393132 T3 ES 2393132T3
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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
- 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
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- A—HUMAN NECESSITIES
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- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- 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
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- 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 | |
| US862552P | 2006-10-23 | ||
| US87138406P | 2006-12-21 | 2006-12-21 | |
| US871384P | 2006-12-21 | ||
| US91375207P | 2007-04-24 | 2007-04-24 | |
| US913752P | 2007-04-24 | ||
| US95283307P | 2007-07-30 | 2007-07-30 | |
| US952833P | 2007-07-30 | ||
| PCT/US2007/081832 WO2008051805A2 (en) | 2006-10-23 | 2007-10-18 | Triazolo-pyridazine protein kinase modulators |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2393132T3 true ES2393132T3 (es) | 2012-12-18 |
Family
ID=39031065
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES07854193T Active ES2393132T3 (es) | 2006-10-23 | 2007-10-18 | Moduoladores de proteína quinasa de triazolopiridazina |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US8071581B2 (https=) |
| EP (1) | EP2081937B1 (https=) |
| JP (1) | JP2010507577A (https=) |
| KR (1) | KR101083177B1 (https=) |
| AU (1) | AU2007309237B2 (https=) |
| BR (1) | BRPI0717317A2 (https=) |
| CA (1) | CA2667453A1 (https=) |
| DK (1) | DK2081937T3 (https=) |
| EA (1) | EA016527B1 (https=) |
| ES (1) | ES2393132T3 (https=) |
| MX (1) | MX2009004060A (https=) |
| PE (1) | PE20081256A1 (https=) |
| PL (1) | PL2081937T3 (https=) |
| PT (1) | PT2081937E (https=) |
| TW (1) | TW200833692A (https=) |
| WO (1) | WO2008051805A2 (https=) |
Families Citing this family (69)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| EP2674428B1 (en) | 2006-04-07 | 2016-04-06 | Vertex Pharmaceuticals Incorporated | Modulators of ATP-binding cassette transporters |
| 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 |
| PE20080403A1 (es) | 2006-07-14 | 2008-04-25 | Amgen Inc | Derivados heterociclicos fusionados y metodos de uso |
| US7683060B2 (en) | 2006-08-07 | 2010-03-23 | Incyte Corporation | Triazolotriazines as kinase inhibitors |
| US8563573B2 (en) | 2007-11-02 | 2013-10-22 | Vertex Pharmaceuticals Incorporated | Azaindole derivatives as CFTR modulators |
| ME02372B (me) | 2006-11-22 | 2016-06-20 | Incyte Holdings Corp | Imidazotriazini i imidazopiramidini kao inhibitori kinaze |
| PE20091468A1 (es) | 2008-02-28 | 2009-10-22 | Novartis Ag | DERIVADOS DE 3-METIL-IMIDAZO-[1,2-b]-PIRIDAZINA |
| WO2009143211A2 (en) * | 2008-05-21 | 2009-11-26 | Incyte Corporation | Salts of 2-fluoro-n-methyl-4-[7-(quinolin-6-yl-methyl)- imidazo[1,2-b][1,2,4]triazin-2-yl]benzamide and processes related to preparing the same |
| 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 |
| DE102008038220A1 (de) | 2008-08-18 | 2010-02-25 | Merck Patent Gmbh | Oxadiazolderivate |
| 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 |
| 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 |
| CA2744563A1 (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 |
| ES2427917T3 (es) * | 2009-02-10 | 2013-11-04 | Astrazeneca Ab | Derivados de triazolo [4,3-b] piridazina y sus usos para el cáncer de próstata |
| US8865719B2 (en) | 2009-03-09 | 2014-10-21 | The Regents Of The University Of California | Substituted heterocycles and their use as allosteric modulators of nicotinic and GABAA receptors |
| US8389526B2 (en) | 2009-08-07 | 2013-03-05 | Novartis Ag | 3-heteroarylmethyl-imidazo[1,2-b]pyridazin-6-yl derivatives |
| JP5781510B2 (ja) | 2009-08-12 | 2015-09-24 | ノバルティス アーゲー | ヘテロ環式ヒドラゾン化合物および癌および炎症の処置のためのそれらの使用 |
| 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 |
| EP3795573B1 (en) * | 2009-12-31 | 2022-07-06 | Hutchison Medipharma Limited | Certain triazolopyrazines, compositions thereof and methods of use therefor |
| EA025304B1 (ru) | 2010-02-03 | 2016-12-30 | Инсайт Холдингс Корпорейшн | ИМИДАЗО[1,2-b][1,2,4]ТРИАЗИНЫ В КАЧЕСТВЕ c-Met ИНГИБИТОРОВ |
| 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 |
| MX353408B (es) * | 2010-04-22 | 2018-01-11 | Vertex Pharma | Proceso para producir compuestos de cicloalquilcarboxamido-indol. |
| WO2011143646A1 (en) | 2010-05-14 | 2011-11-17 | OSI Pharmaceuticals, LLC | Fused bicyclic kinase inhibitors |
| AR081039A1 (es) | 2010-05-14 | 2012-05-30 | Osi Pharmaceuticals Llc | Inhibidores biciclicos fusionados de quinasa |
| JP5960688B2 (ja) | 2010-05-17 | 2016-08-02 | インコゼン セラピューティクス プライベート リミテッド | プロテインキナーゼ調節物質としての新規３，５−二置換−３ｈ−［１，２，３］トリアゾロ［４，５−ｂ］ピリジン化合物 |
| US10414760B2 (en) | 2016-11-29 | 2019-09-17 | Angion Biomedica Corp. | Cytochrome P450 inhibitors and uses thereof |
| CN102985420B (zh) * | 2010-06-01 | 2017-07-04 | 安吉翁生物医药有限公司 | 细胞色素p450抑制剂及其用途 |
| 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 |
| WO2012107500A1 (en) | 2011-02-10 | 2012-08-16 | Novartis Ag | [1, 2, 4] triazolo [4, 3 -b] pyridazine compounds as inhibitors of the c-met tyrosine kinase |
| EP2710003A1 (en) | 2011-05-16 | 2014-03-26 | OSI Pharmaceuticals, LLC | Fused bicyclic kinase inhibitors |
| EA026655B1 (ru) | 2011-09-15 | 2017-05-31 | Новартис Аг | 6-ЗАМЕЩЕННЫЕ 3-(ХИНОЛИН-6-ИЛТИО)[1,2,4]ТРИАЗОЛО[4,3-a]ПИРИДИНЫ В КАЧЕСТВЕ ИНГИБИТОРОВ c-MET ТИРОЗИНКИНАЗЫ |
| US9586963B2 (en) | 2011-09-27 | 2017-03-07 | Genfit | Derivatives of 6-substituted triazolopyridazines as Rev-Erb agonists |
| KR101869534B1 (ko) * | 2012-03-05 | 2018-06-20 | 한국화학연구원 | 신규한 트리아졸로 피리다진 유도체 및 그의 용도 |
| EP2831073B1 (en) | 2012-03-30 | 2020-12-09 | Rhizen Pharmaceuticals S.A. | 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 c-met protein kinases |
| AR092857A1 (es) | 2012-07-16 | 2015-05-06 | Vertex Pharma | Composiciones farmaceuticas de (r)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-il)-n-(1-(2,3-dihidroxipropil)-6-fluoro-2-(1-hidroxi-2-metilpropan-2-il)-1h-indol-5-il)ciclopropancarboxamida y administracion de las mismas |
| 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 |
| MY189505A (en) | 2012-10-16 | 2022-02-16 | Janssen Pharmaceutica Nv | Methylene linked quinolinyl modulators of roryt |
| CA2888485C (en) | 2012-10-16 | 2021-01-26 | Janssen Pharmaceutica Nv | Phenyl linked quinolinyl modulators of ror.gamma.t |
| ES2619610T3 (es) | 2012-10-16 | 2017-06-26 | Janssen Pharmaceutica Nv | Moduladores de ROR-gamma-t de quinolinilo enlazado con heteroarilo |
| US9846345B2 (en) | 2013-02-28 | 2017-12-19 | Empire Technology Development Llc | Colored pigment particles for electrophoretic displays |
| JP6363120B2 (ja) * | 2013-03-13 | 2018-07-25 | エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト | ベンゾオキサゼピン化合物の作製方法 |
| US20140303121A1 (en) | 2013-03-15 | 2014-10-09 | Plexxikon Inc. | Heterocyclic compounds and uses thereof |
| SG11201506687RA (en) | 2013-03-15 | 2015-09-29 | Plexxikon Inc | Heterocyclic compounds and uses thereof |
| US9221804B2 (en) | 2013-10-15 | 2015-12-29 | Janssen Pharmaceutica Nv | Secondary alcohol quinolinyl modulators of RORγt |
| US9403816B2 (en) | 2013-10-15 | 2016-08-02 | Janssen Pharmaceutica Nv | Phenyl linked quinolinyl modulators of RORγt |
| BR112016008215A2 (pt) | 2013-10-15 | 2017-09-26 | Janssen Pharmaceutica Nv | moduladores de quinolinila ligados por alquila de roryt |
| 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 |
| 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 |
| RU2744460C2 (ru) | 2014-04-15 | 2021-03-09 | Вертекс Фармасьютикалз Инкорпорейтед | Фармацевтические композиции для лечения заболеваний, опосредованных муковисцидозным трансмембранным регулятором проводимости |
| CA2957785C (en) | 2014-08-11 | 2023-01-03 | Angion Biomedica Corporation | Cytochrome p450 inhibitors and uses thereof |
| JP2018501279A (ja) | 2014-12-31 | 2018-01-18 | アンギオン バイオメディカ コーポレイション | 疾患を治療するための方法及び薬剤 |
| BR112017020952A2 (pt) * | 2015-04-13 | 2018-07-10 | Five Prime Therapeutics Inc | método de tratamento de câncer, composição e uso da composição |
| AR105392A1 (es) | 2015-07-20 | 2017-09-27 | Genzyme Corp | Inhibidores del receptor del factor estimulador de colonias 1 (csf-1r) |
| JP7675519B2 (ja) | 2017-10-13 | 2025-05-13 | オプナ バイオ ソシエテ アノニム | キナーゼを調節するための化合物の固体形態 |
| 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 |
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| WO2002083139A1 (en) * | 2001-04-10 | 2002-10-24 | Merck & Co., Inc. | Inhibitors of akt activity |
| WO2002083675A2 (en) | 2001-04-10 | 2002-10-24 | Merck Sharp & Dohme Limited | Inhibitors of akt activity |
| WO2003014649A1 (en) * | 2001-08-10 | 2003-02-20 | Yokohama Tlo Company Ltd. | Heat transfer device |
| HUE030390T2 (en) * | 2005-12-21 | 2017-05-29 | Janssen Pharmaceutica Nv | Triazolopyridazines as tyrosine kinase modulators |
| JP2009538899A (ja) * | 2006-05-30 | 2009-11-12 | ファイザー・プロダクツ・インク | トリアゾロピリダジン誘導体 |
| PE20080403A1 (es) * | 2006-07-14 | 2008-04-25 | Amgen Inc | Derivados heterociclicos fusionados y metodos de uso |
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2007
- 2007-10-18 CA CA002667453A patent/CA2667453A1/en not_active Abandoned
- 2007-10-18 AU AU2007309237A patent/AU2007309237B2/en not_active Ceased
- 2007-10-18 JP JP2009533536A patent/JP2010507577A/ja not_active Withdrawn
- 2007-10-18 PL PL07854193T patent/PL2081937T3/pl unknown
- 2007-10-18 US US12/442,987 patent/US8071581B2/en not_active Expired - Fee Related
- 2007-10-18 PT PT07854193T patent/PT2081937E/pt unknown
- 2007-10-18 DK DK07854193.5T patent/DK2081937T3/da active
- 2007-10-18 MX MX2009004060A patent/MX2009004060A/es not_active Application Discontinuation
- 2007-10-18 BR BRPI0717317-2A2A patent/BRPI0717317A2/pt not_active IP Right Cessation
- 2007-10-18 ES ES07854193T patent/ES2393132T3/es active Active
- 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 EP EP07854193A patent/EP2081937B1/en active Active
- 2007-10-18 WO PCT/US2007/081832 patent/WO2008051805A2/en not_active Ceased
- 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 |
|---|---|
| US8071581B2 (en) | 2011-12-06 |
| MX2009004060A (es) | 2009-06-19 |
| WO2008051805A3 (en) | 2008-07-10 |
| JP2010507577A (ja) | 2010-03-11 |
| PT2081937E (pt) | 2012-10-15 |
| WO2008051805A2 (en) | 2008-05-02 |
| PE20081256A1 (es) | 2008-10-13 |
| US20100120739A1 (en) | 2010-05-13 |
| TW200833692A (en) | 2008-08-16 |
| EP2081937A2 (en) | 2009-07-29 |
| EP2081937B1 (en) | 2012-09-12 |
| PL2081937T3 (pl) | 2013-01-31 |
| BRPI0717317A2 (pt) | 2013-10-22 |
| CA2667453A1 (en) | 2008-05-02 |
| DK2081937T3 (da) | 2012-10-01 |
| KR101083177B1 (ko) | 2011-11-11 |
| AU2007309237B2 (en) | 2012-03-22 |
| EA016527B1 (ru) | 2012-05-30 |
| KR20090069303A (ko) | 2009-06-30 |
| EA200970402A1 (ru) | 2009-10-30 |
| AU2007309237A1 (en) | 2008-05-02 |
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