JP2010507577A - トリアゾロピリダジンタンパク質キナーゼモジュレーター - Google Patents
トリアゾロピリダジンタンパク質キナーゼモジュレーター Download PDFInfo
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- JP2010507577A JP2010507577A JP2009533536A JP2009533536A JP2010507577A JP 2010507577 A JP2010507577 A JP 2010507577A JP 2009533536 A JP2009533536 A JP 2009533536A JP 2009533536 A JP2009533536 A JP 2009533536A JP 2010507577 A JP2010507577 A JP 2010507577A
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- substituted
- unsubstituted
- alkyl
- pyridinyl
- halogen
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- CBHTTYDJRXOHHL-UHFFFAOYSA-N 2h-triazolo[4,5-c]pyridazine Chemical compound N1=NC=CC2=C1N=NN2 CBHTTYDJRXOHHL-UHFFFAOYSA-N 0.000 title abstract description 20
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- 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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- 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
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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
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- 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
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- Nitrogen Condensed Heterocyclic Rings (AREA)
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| JP2011524385A (ja) * | 2008-06-18 | 2011-09-01 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング | Metキナーゼ阻害剤としての3−(3−ピリミジン−2−イルベンジル)−1,2,4−トリアゾロ[4,3−b]ピリダジン誘導体 |
| JP2012512200A (ja) * | 2008-12-18 | 2012-05-31 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング | 3−(3−ピリミジン−2−イルベンジル)−1,2,4−トリアゾロ[4,3−b]ピリミジン誘導体 |
| JP2013525371A (ja) * | 2010-04-22 | 2013-06-20 | バーテックス ファーマシューティカルズ インコーポレイテッド | シクロアルキルカルボキサミド−インドール化合物の製造方法 |
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| JP2015526486A (ja) * | 2012-09-03 | 2015-09-10 | クラウン バイオサイエンス インコーポレイテッド(台湾) | 抗がん剤としての高選択性c−Met阻害剤 |
| JP2016512209A (ja) * | 2013-03-13 | 2016-04-25 | 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 |
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| ES2882684T3 (es) | 2006-04-07 | 2021-12-02 | Vertex Pharma | Preparación de moduladores de transportadores del casete de unión a ATP |
| US7645789B2 (en) | 2006-04-07 | 2010-01-12 | Vertex Pharmaceuticals Incorporated | Indole derivatives as CFTR modulators |
| USRE50453E1 (en) | 2006-04-07 | 2025-06-10 | Vertex Pharmaceuticals Incorporated | Indole derivatives as CFTR modulators |
| 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 |
| 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 |
| GEP20125658B (en) | 2006-11-22 | 2012-10-10 | Incyte Corp | Imidazotriazines and imidazo pyrimidines as kinase inhibitors |
| AR070487A1 (es) | 2008-02-28 | 2010-04-07 | Novartis Ag | Derivados de 3- metil- imidazo -( 1,2-b)- piridazina |
| CN103936743B (zh) * | 2008-05-21 | 2018-04-24 | 因西特控股公司 | 2-氟-N-甲基-4-[7-(喹啉-6-基甲基)咪唑并[1,2-b][1,2,4]三嗪-2-基]苯甲酰胺的盐及与其相关的制备方法 |
| DE102008037790A1 (de) | 2008-08-14 | 2010-02-18 | Merck Patent Gmbh | Bicyclische Triazolderivate |
| DE102008038222A1 (de) | 2008-08-18 | 2010-02-25 | Merck Patent Gmbh | Indazol-5-carbonsäurehydrazid-derivate |
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| DE102008038220A1 (de) | 2008-08-18 | 2010-02-25 | Merck Patent Gmbh | Oxadiazolderivate |
| 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 |
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| 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 |
| EA019647B1 (ru) * | 2009-02-10 | 2014-05-30 | Астразенека Аб | ПРОИЗВОДНЫЕ ТРИАЗОЛО[4,3-b]ПИРИДАЗИНА И ИХ ПРИМЕНЕНИЕ ДЛЯ ЛЕЧЕНИЯ РАКА ПРЕДСТАТЕЛЬНОЙ ЖЕЛЕЗЫ |
| CA2754180A1 (en) * | 2009-03-09 | 2010-09-16 | 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 |
| MX2012002179A (es) | 2009-08-20 | 2012-03-16 | Novartis Ag | Compuestos heterociclicos de oxima. |
| EP2719699B1 (en) * | 2009-12-31 | 2015-07-08 | 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 |
| 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 |
| ES2715611T3 (es) | 2010-05-17 | 2019-06-05 | Incozen Therapeutics Pvt Ltd | Compuestos novedosos de 3H-imidazo[4,5-b]piridina-3,5-disustituida y 3H-[1,2,3]triazolo[4,5-b]piridina 3,5-disustituida como moduladores de proteína cinasas |
| US10414760B2 (en) | 2016-11-29 | 2019-09-17 | 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 |
| US20130324526A1 (en) | 2011-02-10 | 2013-12-05 | 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 |
| WO2013038362A1 (en) | 2011-09-15 | 2013-03-21 | Novartis Ag | 6 - substituted 3 - (quinolin- 6 - ylthio) - [1,2,4] triazolo [4, 3 -a] pyradines as tyrosine kinase |
| 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 |
| KR102164317B1 (ko) | 2012-03-30 | 2020-10-13 | 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 |
| US9012496B2 (en) | 2012-07-16 | 2015-04-21 | Vertex Pharmaceuticals Incorporated | Pharmaceutical compositions of (R)-1-(2,2-difluorobenzo[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 |
| PE20150778A1 (es) | 2012-10-16 | 2015-05-23 | Janssen Pharmaceutica Nv | Moduladores de quinolinilo unidos a metileno de ror-gamma-t |
| PE20151203A1 (es) | 2012-10-16 | 2015-08-31 | Janssen Pharmaceutica Nv | MODULADORES DE QUINOLINILO UNIDOS A FENILO DE ROR-GAMMA-t |
| KR20150070348A (ko) | 2012-10-16 | 2015-06-24 | 얀센 파마슈티카 엔.브이. | RoRγt의 헤테로아릴 결합 퀴놀리닐 조절제 |
| WO2014133526A1 (en) | 2013-02-28 | 2014-09-04 | Empire Technology Development Llc | Colored pigment particles for electrophoretic displays |
| US20140303121A1 (en) | 2013-03-15 | 2014-10-09 | Plexxikon Inc. | Heterocyclic compounds and uses thereof |
| RU2680100C9 (ru) | 2013-03-15 | 2019-04-18 | Плексксикон Инк. | Гетероциклические соединения и их применения |
| 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 |
| US9624225B2 (en) | 2013-10-15 | 2017-04-18 | Janssen Pharmaceutica Nv | Quinolinyl modulators of RORγt |
| US10555941B2 (en) | 2013-10-15 | 2020-02-11 | Janssen Pharmaceutica Nv | Alkyl linked quinolinyl modulators of RORγt |
| US9346782B2 (en) | 2013-10-15 | 2016-05-24 | Janssen Pharmaceutica Nv | Alkyl linked quinolinyl modulators of RORγt |
| US9284308B2 (en) | 2013-10-15 | 2016-03-15 | Janssen Pharmaceutica Nv | Methylene linked quinolinyl modulators of RORγt |
| US9328095B2 (en) | 2013-10-15 | 2016-05-03 | Janssen Pharmaceutica Nv | Heteroaryl linked quinolinyl modulators of RORgammat |
| 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 |
| PT3131582T (pt) | 2014-04-15 | 2018-10-08 | Vertex Pharma | Composições farmacêuticas para o tratamento de doenças mediadas pelo regulador de condutância transmembranar da fibrose quística |
| ES2886641T3 (es) | 2014-08-11 | 2021-12-20 | Angion Biomedica Corp | Inhibidores de citocromo P450 y sus usos |
| US10287282B2 (en) | 2014-12-31 | 2019-05-14 | Angion Biomedica Corp. | Methods and agents for treating disease |
| LT3283527T (lt) | 2015-04-13 | 2021-03-25 | Five Prime Therapeutics, Inc. | Kompleksinė terapija vėžio gydymui |
| WO2017015267A1 (en) | 2015-07-20 | 2017-01-26 | Genzyme Corporation | Colony stimulating factor-1 receptor (csf-1r) inhibitors |
| US10717735B2 (en) | 2017-10-13 | 2020-07-21 | 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 |
|---|---|---|---|---|
| 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 |
| JP4115390B2 (ja) * | 2001-08-10 | 2008-07-09 | よこはまティーエルオー株式会社 | 伝熱装置 |
| AU2006331912B2 (en) * | 2005-12-21 | 2012-08-30 | Janssen Pharmaceutica, N.V. | Triazolopyridazines as tyrosine kinase modulators |
| CA2651979A1 (en) * | 2006-05-30 | 2007-12-06 | Pfizer Products Inc. | Triazolopyridazine derivatives |
| PE20121506A1 (es) * | 2006-07-14 | 2012-11-26 | Amgen Inc | Compuestos triazolopiridinas como inhibidores de c-met |
-
2007
- 2007-10-18 EA EA200970402A patent/EA016527B1/ru not_active IP Right Cessation
- 2007-10-18 ES ES07854193T patent/ES2393132T3/es active Active
- 2007-10-18 PL PL07854193T patent/PL2081937T3/pl unknown
- 2007-10-18 PT PT07854193T patent/PT2081937E/pt unknown
- 2007-10-18 CA CA002667453A patent/CA2667453A1/en not_active Abandoned
- 2007-10-18 DK DK07854193.5T patent/DK2081937T3/da active
- 2007-10-18 AU AU2007309237A patent/AU2007309237B2/en not_active Ceased
- 2007-10-18 MX MX2009004060A patent/MX2009004060A/es not_active Application Discontinuation
- 2007-10-18 JP JP2009533536A patent/JP2010507577A/ja not_active Withdrawn
- 2007-10-18 KR KR1020097007986A patent/KR101083177B1/ko not_active Expired - Fee Related
- 2007-10-18 WO PCT/US2007/081832 patent/WO2008051805A2/en not_active Ceased
- 2007-10-18 EP EP07854193A patent/EP2081937B1/en active Active
- 2007-10-18 US US12/442,987 patent/US8071581B2/en not_active Expired - Fee Related
- 2007-10-18 BR BRPI0717317-2A2A patent/BRPI0717317A2/pt not_active IP Right Cessation
- 2007-10-22 TW TW096139481A patent/TW200833692A/zh unknown
- 2007-10-23 PE PE2007001436A patent/PE20081256A1/es not_active Application Discontinuation
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011524385A (ja) * | 2008-06-18 | 2011-09-01 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング | Metキナーゼ阻害剤としての3−(3−ピリミジン−2−イルベンジル)−1,2,4−トリアゾロ[4,3−b]ピリダジン誘導体 |
| JP2012512200A (ja) * | 2008-12-18 | 2012-05-31 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング | 3−(3−ピリミジン−2−イルベンジル)−1,2,4−トリアゾロ[4,3−b]ピリミジン誘導体 |
| JP2013525371A (ja) * | 2010-04-22 | 2013-06-20 | バーテックス ファーマシューティカルズ インコーポレイテッド | シクロアルキルカルボキサミド−インドール化合物の製造方法 |
| JP2013527238A (ja) * | 2010-06-01 | 2013-06-27 | アンジオン バイオメディカ コーポレーション | チトクロームp450阻害剤およびその使用 |
| JP2015526486A (ja) * | 2012-09-03 | 2015-09-10 | クラウン バイオサイエンス インコーポレイテッド(台湾) | 抗がん剤としての高選択性c−Met阻害剤 |
| JP2016512209A (ja) * | 2013-03-13 | 2016-04-25 | 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 |
| JP2018008959A (ja) * | 2013-03-13 | 2018-01-18 | 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 |
| KR101871133B1 (ko) | 2013-03-13 | 2018-06-25 | 에프. 호프만-라 로슈 아게 | 벤즈옥사제핀 화합물의 제조 방법 |
| JP2017503770A (ja) * | 2013-12-09 | 2017-02-02 | ユーシービー バイオファルマ エスピーアールエル | Tnf活性のモジュレーターとしてのトリアゾロピリダジン誘導体 |
Also Published As
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|---|---|
| PL2081937T3 (pl) | 2013-01-31 |
| TW200833692A (en) | 2008-08-16 |
| US8071581B2 (en) | 2011-12-06 |
| MX2009004060A (es) | 2009-06-19 |
| PE20081256A1 (es) | 2008-10-13 |
| ES2393132T3 (es) | 2012-12-18 |
| DK2081937T3 (da) | 2012-10-01 |
| CA2667453A1 (en) | 2008-05-02 |
| PT2081937E (pt) | 2012-10-15 |
| EA200970402A1 (ru) | 2009-10-30 |
| BRPI0717317A2 (pt) | 2013-10-22 |
| EP2081937B1 (en) | 2012-09-12 |
| WO2008051805A3 (en) | 2008-07-10 |
| EP2081937A2 (en) | 2009-07-29 |
| US20100120739A1 (en) | 2010-05-13 |
| AU2007309237A1 (en) | 2008-05-02 |
| AU2007309237B2 (en) | 2012-03-22 |
| EA016527B1 (ru) | 2012-05-30 |
| KR20090069303A (ko) | 2009-06-30 |
| KR101083177B1 (ko) | 2011-11-11 |
| WO2008051805A2 (en) | 2008-05-02 |
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