CA2590294A1 - Pyrido pyrimidinones, dihydro pyrimido pyrimidinones and pteridinones useful as raf kinase inhibitors - Google Patents
Pyrido pyrimidinones, dihydro pyrimido pyrimidinones and pteridinones useful as raf kinase inhibitors Download PDFInfo
- Publication number
- CA2590294A1 CA2590294A1 CA002590294A CA2590294A CA2590294A1 CA 2590294 A1 CA2590294 A1 CA 2590294A1 CA 002590294 A CA002590294 A CA 002590294A CA 2590294 A CA2590294 A CA 2590294A CA 2590294 A1 CA2590294 A1 CA 2590294A1
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- heteroaryl
- aryl
- compound
- heteroalkyl
- 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
Links
- 108010077182 raf Kinases Proteins 0.000 title claims description 17
- 102000009929 raf Kinases Human genes 0.000 title claims description 17
- 229940043355 kinase inhibitor Drugs 0.000 title description 4
- 239000003757 phosphotransferase inhibitor Substances 0.000 title description 4
- IAAQUOVTPAMQCR-UHFFFAOYSA-N 1h-pyrido[3,2-d]pyrimidin-2-one Chemical class C1=CC=C2NC(=O)N=CC2=N1 IAAQUOVTPAMQCR-UHFFFAOYSA-N 0.000 title description 3
- VWXIHLCLIOQWRA-UHFFFAOYSA-N 1h-pteridin-2-one Chemical class N1=CC=NC2=NC(O)=NC=C21 VWXIHLCLIOQWRA-UHFFFAOYSA-N 0.000 title 1
- VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical class OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 552
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- 230000001404 mediated effect Effects 0.000 claims abstract description 17
- 102000001253 Protein Kinase Human genes 0.000 claims abstract description 15
- 108060006633 protein kinase Proteins 0.000 claims abstract description 15
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- 125000003118 aryl group Chemical group 0.000 claims description 430
- 125000001072 heteroaryl group Chemical group 0.000 claims description 422
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- 238000000034 method Methods 0.000 claims description 35
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 35
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 35
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- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 2
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Classifications
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D475/00—Heterocyclic compounds containing pteridine ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D475/00—Heterocyclic compounds containing pteridine ring systems
- C07D475/06—Heterocyclic compounds containing pteridine ring systems with a nitrogen atom directly attached in position 4
-
- 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
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Landscapes
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Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US63564404P | 2004-12-13 | 2004-12-13 | |
| US60/635,644 | 2004-12-13 | ||
| US63674004P | 2004-12-16 | 2004-12-16 | |
| US60/636,740 | 2004-12-16 | ||
| US11/301,311 US7767687B2 (en) | 2004-12-13 | 2005-12-12 | Pyrido pyrimidinones, dihydro pyrimido pyrimidinones and pteridinones useful as RAF kinase inhibitors |
| PCT/US2005/044804 WO2006065703A1 (en) | 2004-12-13 | 2005-12-12 | Pyrido pyrimidinones, dihydro pyrimido pyrimidinones and pteridinones useful as raf kinase inhibitors |
| US11/301,311 | 2005-12-12 |
Publications (1)
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| CA2590294A1 true CA2590294A1 (en) | 2006-06-22 |
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| CA002590294A Abandoned CA2590294A1 (en) | 2004-12-13 | 2005-12-12 | Pyrido pyrimidinones, dihydro pyrimido pyrimidinones and pteridinones useful as raf kinase inhibitors |
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| Country | Link |
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| US (2) | US7767687B2 (enExample) |
| EP (1) | EP1828186A1 (enExample) |
| JP (1) | JP5111113B2 (enExample) |
| AU (1) | AU2005316668B2 (enExample) |
| CA (1) | CA2590294A1 (enExample) |
| WO (1) | WO2006065703A1 (enExample) |
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| UY29439A1 (es) * | 2005-03-25 | 2006-10-02 | Glaxo Group Ltd | Nuevos compuestos |
| WO2007038215A1 (en) | 2005-09-22 | 2007-04-05 | Incyte Corporation | Tetracyclic inhibitors of janus kinases |
| PT1940839E (pt) | 2005-10-07 | 2013-10-10 | Exelixis Inc | Inibidores de piridopirimidinona pi3k alfa |
| HRP20130902T1 (hr) | 2005-10-07 | 2013-11-08 | Exelixis Inc. | PIRIDOPIRIMIDINONSKI INHIBITORI PI3Kalfa |
| WO2007067444A1 (en) | 2005-12-08 | 2007-06-14 | Millennium Pharmaceuticals, Inc. | Bicyclic compounds with kinase inhibitory activity |
| CA2663401C (en) | 2006-09-15 | 2011-07-12 | Pfizer Products Inc. | Pyrido (2, 3-d) pyrimidinone compounds and their use as pi3 inhibitors |
| ES2627352T3 (es) | 2006-10-19 | 2017-07-27 | Signal Pharmaceuticals, Llc | Compuestos heteroarilo, sus composiciones y su uso como inhibidores de proteínas quinasas |
| TW200835497A (en) * | 2007-01-11 | 2008-09-01 | Astrazeneca Ab | Chemical compounds 636 |
| JP2010517989A (ja) | 2007-02-01 | 2010-05-27 | アストラゼネカ アクチボラグ | Ｈｓｐ９０阻害剤としての５，６，７，８−テトラヒドロプテリジン誘導体 |
| JP5238172B2 (ja) * | 2007-03-22 | 2013-07-17 | 公益財団法人相模中央化学研究所 | パーフルオロアルキル基を有する含窒素六員環化合物およびその製造方法 |
| CL2008001933A1 (es) * | 2007-06-29 | 2009-09-25 | Millennium Pharm Inc | Compuestos derivados de pirimidina, inhibidores de la raf quinasa; compuestos intermediarios; procedimiento de preparacion; composicion farmaceutica; y su uso para tratar trastornos proliferativos, cardiacos, neurodegenerativos, inflamatorios, oseos, inmunologicos enfermedad viral, entre otros. |
| EP2167497A2 (en) * | 2007-06-29 | 2010-03-31 | Sunesis Pharmaceuticals, Inc. | Heterocyclic compounds useful as raf kinase inhibitors |
| AU2009289649B2 (en) | 2008-09-03 | 2016-05-05 | Biomarin Pharmaceutical Inc. | Compositions including 6-aminohexanoic acid derivatives as HDAC inhibitors |
| TW201018685A (en) | 2008-09-30 | 2010-05-16 | Exelixis Inc | Pyridopyrimidinone inhibitors of PI3Kα and mTOR |
| US8110578B2 (en) | 2008-10-27 | 2012-02-07 | Signal Pharmaceuticals, Llc | Pyrazino[2,3-b]pyrazine mTOR kinase inhibitors for oncology indications and diseases associated with the mTOR/PI3K/Akt pathway |
| JP2012514044A (ja) * | 2008-12-30 | 2012-06-21 | ミレニアム ファーマシューティカルズ， インコーポレイテッド | Ｒａｆキナーゼ阻害剤として有用なヘテロアリール化合物 |
| BR112012011328A2 (pt) * | 2009-10-23 | 2016-11-22 | Lilly Co Eli | inibidores de akt |
| NZ599549A (en) | 2009-10-26 | 2013-11-29 | Signal Pharm Llc | Methods of synthesis and purification of heteroaryl compounds |
| BR112012019459A2 (pt) | 2010-02-03 | 2017-10-17 | Signal Pharm Llc | identificação de mutação de lkb1 como um biomarcador preditivo para sensibilidade para inibidores de tor quinase. |
| UY33221A (es) | 2010-02-09 | 2011-09-30 | Univ California | MÉTODOS PARA TRATAR CÁNCER USANDO INHIBIDORES DE PI3K Y mTOR EN COMBINACIÓN CON INHIBIDORES DE AUTOFAGIA |
| WO2012088266A2 (en) | 2010-12-22 | 2012-06-28 | Incyte Corporation | Substituted imidazopyridazines and benzimidazoles as inhibitors of fgfr3 |
| US8957066B2 (en) | 2011-02-28 | 2015-02-17 | Biomarin Pharmaceutical Inc. | Histone deacetylase inhibitors |
| US10059723B2 (en) | 2011-02-28 | 2018-08-28 | Biomarin Pharmaceutical Inc. | Histone deacetylase inhibitors |
| WO2012118782A1 (en) | 2011-02-28 | 2012-09-07 | Repligen Corporation | Histone deacetylase inhibitors |
| JP2014528410A (ja) * | 2011-09-30 | 2014-10-27 | キネタ・インコーポレイテツド | 抗ウイルス化合物 |
| CN103998036B (zh) | 2011-10-19 | 2017-05-31 | 西格诺药品有限公司 | 利用tor激酶抑制剂治疗癌症 |
| BR112014013332B1 (pt) | 2011-12-02 | 2022-09-06 | Signal Pharmaceuticals, Llc | Composições farmacêuticas de 7-(6-(2-hidroxi-propan-2-il)piridin-3-il)-1-((trans)-4- metoxicicloexil)-3,4-diidropirazino [2,3-b]pirazin-2(1h)-ona, uma forma sólida dessa e métodos de seu uso |
| DK2797888T3 (en) | 2011-12-31 | 2016-09-19 | Beigene Ltd | Fused tricyclic compounds as RAF kinase inhibitors |
| CN104271159B (zh) | 2012-02-24 | 2017-11-28 | 西格诺药品有限公司 | 利用tor激酶抑制剂联合治疗来治疗非小细胞肺癌的方法 |
| CA2876689C (en) | 2012-06-13 | 2022-04-26 | Incyte Corporation | Substituted tricyclic compounds as fgfr inhibitors |
| US9388185B2 (en) | 2012-08-10 | 2016-07-12 | Incyte Holdings Corporation | Substituted pyrrolo[2,3-b]pyrazines as FGFR inhibitors |
| AU2013203714B2 (en) | 2012-10-18 | 2015-12-03 | Signal Pharmaceuticals, Llc | Inhibition of phosphorylation of PRAS40, GSK3-beta or P70S6K1 as a marker for TOR kinase inhibitory activity |
| US9266892B2 (en) | 2012-12-19 | 2016-02-23 | Incyte Holdings Corporation | Fused pyrazoles as FGFR inhibitors |
| SG11201505446WA (en) | 2013-01-16 | 2015-08-28 | Signal Pharm Llc | Substituted pyrrolopyrimidine compounds, compositions thereof, and methods of treatment therewith |
| TWI647220B (zh) | 2013-03-15 | 2019-01-11 | 美商西建卡爾有限責任公司 | 雜芳基化合物及其用途 |
| MY181020A (en) | 2013-03-15 | 2020-12-16 | Sanofi Sa | Heteroaryl compounds and uses thereof |
| RU2665554C2 (ru) | 2013-03-15 | 2018-08-31 | Байомарин Фармасьютикал Инк. | Ингибиторы hdac |
| EP3549940A1 (en) | 2013-04-17 | 2019-10-09 | Signal Pharmaceuticals, LLC | Pharmaceutical formulations, of 1-ethyl-7-(2-methyl-6-(1h-1,2,4-triazol-3-yl) pyridin-3-yl) -3,4-dihydropyrazino[2,3-b]pyrazin-2(1h)-one |
| WO2014172436A1 (en) | 2013-04-17 | 2014-10-23 | Signal Pharmaceuticals, Llc | Combination therapy comprising a tor kinase inhibitor and a 5-substituted quinazolinone compound for treating cancer |
| JP6382946B2 (ja) | 2013-04-17 | 2018-08-29 | シグナル ファーマシューティカルズ，エルエルシー | ジヒドロピラジノ−ピラジンによる癌治療 |
| MY189663A (en) | 2013-04-17 | 2022-02-23 | Signal Pharm Llc | Combination therapy comprising a dihydropyrazino-pyrazine compound and an androgen receptor antagonist for treating prostate cancer |
| WO2014172425A1 (en) | 2013-04-17 | 2014-10-23 | Signal Pharmaceuticals, Llc | Treatment of cancer with dihydropyrazino-pyrazines |
| CA2908742C (en) | 2013-04-17 | 2021-06-01 | Signal Pharmaceuticals, Llc | Combination therapy comprising a tor kinase inhibitor and a cytidine analog for treating cancer |
| HK1221168A1 (zh) | 2013-04-17 | 2017-05-26 | 西格诺药品有限公司 | 用於治疗癌症的包括tor激酶抑制剂和n-(3-(5-氟-2-(4-(2-甲氧基乙氧基)苯基氨基)嘧啶-4-基氨基)苯基)丙烯醯胺的组合疗法 |
| PH12015502383B1 (en) | 2013-04-19 | 2023-02-03 | Incyte Holdings Corp | Bicyclic heterocycles as fgfr inhibitors |
| AU2014267360B2 (en) | 2013-05-14 | 2018-07-05 | Active Biotech Ab | N-(heteroaryl)-sulfonamide derivatives useful as S100-inhibitors |
| CN107474051B (zh) | 2013-05-29 | 2020-10-30 | 西格诺药品有限公司 | 二氢吡嗪并吡嗪化合物的药物组合物、其固体形式和它们的用途 |
| WO2015000715A1 (en) | 2013-07-02 | 2015-01-08 | Syngenta Participations Ag | Pesticidally active bi- or tricyclic heterocycles with sulfur containing substituents |
| PL3089971T3 (pl) | 2014-01-01 | 2021-01-25 | Medivation Technologies Llc | Związki i sposoby ich zastosowania |
| MA38393B1 (fr) | 2014-03-13 | 2018-11-30 | Sanofi Sa | Composés hétéroaryle et utilisations associées |
| NZ714742A (en) | 2014-04-16 | 2017-04-28 | Signal Pharm Llc | Solid forms of 1-ethyl-7-(2-methyl-6-(1h-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1h)-one, compositions thereof and methods of their use |
| WO2015160880A1 (en) | 2014-04-16 | 2015-10-22 | Signal Pharmaceuticals, Llc | SOLID FORMS COMPRISING 1-ETHYL-7-(2-METHYL-6-(1H-1,2,4-TRIAZOL-3-YL) PYRIDIN-3-YL)-3,4-DIHYDROPYRAZINO(2,3-b)PYRAZIN-2(1H)-ONE, AND A COFORMER, COMPOSITIONS AND METHODS OF USE THEREOF |
| EP3131552B1 (en) | 2014-04-16 | 2020-07-15 | Signal Pharmaceuticals, LLC | Methods for treating cancer using tor kinase inhibitor combination therapy |
| US9718824B2 (en) | 2014-04-16 | 2017-08-01 | Signal Pharmaceuticals, Llc | Solid forms comprising 7-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)-1-((trans)-4-methoxycyclohexyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one, and a coformer, compositions and methods of use thereof |
| WO2016010886A1 (en) | 2014-07-14 | 2016-01-21 | Signal Pharmaceuticals, Llc | Methods of treating a cancer using substituted pyrrolopyrimidine compounds, compositions thereof |
| NZ629796A (en) | 2014-07-14 | 2015-12-24 | Signal Pharm Llc | Amorphous form of 4-((4-(cyclopentyloxy)-5-(2-methylbenzo[d]oxazol-6-yl)-7h-pyrrolo[2,3-d]pyrimidin-2-yl)amino)-3-methoxy-n-methylbenzamide, compositions thereof and methods of their use |
| BR112017002598B1 (pt) | 2014-08-12 | 2022-03-03 | Syngenta Participations Ag | Derivados heterocíclicos ativos do ponto de vista pesticida com substituintes contendo enxofre |
| US10851105B2 (en) | 2014-10-22 | 2020-12-01 | Incyte Corporation | Bicyclic heterocycles as FGFR4 inhibitors |
| BR112017012232B1 (pt) | 2014-12-11 | 2021-08-17 | Syngenta Participations Ag | Derivados tetraciclicos ativos em termos pesticidas com substituintes contendo enxofre |
| UY36547A (es) | 2015-02-05 | 2016-06-01 | Bayer Cropscience Ag | Derivados heterocíclicos condensados bicíclicos sustituidos por 2-(het)arilo como pesticidas |
| UY36548A (es) | 2015-02-05 | 2016-06-01 | Bayer Cropscience Ag | Derivados heterocíclicos condensados bicíclicos sustituidos por 2-(het)arilo como pesticidas |
| CA2976790C (en) | 2015-02-20 | 2024-02-27 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
| US9580423B2 (en) | 2015-02-20 | 2017-02-28 | Incyte Corporation | Bicyclic heterocycles as FGFR4 inhibitors |
| MA41551A (fr) | 2015-02-20 | 2017-12-26 | Incyte Corp | Hétérocycles bicycliques utilisés en tant qu'inhibiteurs de fgfr4 |
| ES2779532T3 (es) | 2015-04-08 | 2020-08-18 | Bayer Cropscience Ag | Derivados de imidazo[1,2a]piridin-2-ilo como pesticidas y sus productos intermedios |
| AU2016248376B2 (en) | 2015-04-15 | 2020-10-08 | Beone Medicines I Gmbh | Maleate salts of a B-RAF kinase inhibitor, crystalline forms, methods of preparation, and uses therefore |
| JP6689297B2 (ja) | 2015-07-23 | 2020-04-28 | 武田薬品工業株式会社 | 複素環化合物 |
| AR105607A1 (es) | 2015-08-07 | 2017-10-18 | Bayer Cropscience Ag | Derivados heterocíclicos condensados sustituidos por 2-(het)arilo como pesticidas |
| CN108430986B (zh) | 2015-10-26 | 2021-08-31 | 拜耳作物科学股份公司 | 作为有害生物控制剂的稠合双环杂环衍生物 |
| BR112018010347A2 (pt) | 2015-11-23 | 2018-12-04 | Syngenta Participations Ag | derivados heterocíclicos ativos em termos pesticidas com substituintes contendo enxofre e ciclopropila |
| WO2017093180A1 (de) | 2015-12-01 | 2017-06-08 | Bayer Cropscience Aktiengesellschaft | Kondensierte bicyclische heterocyclen-derivate als schädlingsbekämpfungsmittel |
| JP6175519B2 (ja) * | 2016-01-04 | 2017-08-09 | ベイジーン リミテッド | Ｒａｆキナーゼ阻害剤としての縮合三環式化合物 |
| WO2017144341A1 (de) | 2016-02-23 | 2017-08-31 | Bayer Cropscience Aktiengesellschaft | Kondensierte bicyclische heterocyclen-derivate als schädlingsbekämpfungsmittel |
| WO2017174414A1 (de) | 2016-04-05 | 2017-10-12 | Bayer Cropscience Aktiengesellschaft | Naphthalin-derivate als schädlingsbekämpfungsmittel |
| EP3241830A1 (de) | 2016-05-04 | 2017-11-08 | Bayer CropScience Aktiengesellschaft | Kondensierte bicyclische heterocyclen-derivate als schädlingsbekämpfungsmittel |
| WO2018007885A1 (en) | 2016-07-05 | 2018-01-11 | Beigene, Ltd. | COMBINATION OF A PD-l ANTAGONIST AND A RAF INHIBITOR FOR TREATING CANCER |
| US10561145B2 (en) | 2016-07-19 | 2020-02-18 | Bayer Cropscience Aktiengesellschaft | Fused bicyclic heterocycle derivatives as pesticides |
| AU2017314083B2 (en) | 2016-08-15 | 2020-12-10 | Bayer Aktiengesellschaft | Condensed bicyclic heterocycle derivatives as pest control agents |
| CN109819653A (zh) | 2016-08-16 | 2019-05-28 | 拜耳作物科学股份公司 | 制备2-(3,6-二卤代吡啶-2-基)-3H-咪唑[4,5-c]吡啶衍生物的方法以及通过3H-咪唑[4,5-c]吡啶衍生物与有机金属锌胺碱的反应得到的相关化合物 |
| CN109963860A (zh) | 2016-09-19 | 2019-07-02 | 拜耳作物科学股份公司 | 吡唑并[1,5-a]吡啶衍生物及其作为农药的用途 |
| WO2018065292A1 (de) | 2016-10-06 | 2018-04-12 | Bayer Cropscience Aktiengesellschaft | 2-(het)aryl-substituierte kondensierte bicyclische heterocyclen-derivate als schädlings-bekämpfungsmittel |
| CN117624038A (zh) | 2016-12-01 | 2024-03-01 | 先正达参股股份有限公司 | 具有含硫取代基的杀有害生物活性杂环衍生物 |
| US20200077658A1 (en) | 2016-12-16 | 2020-03-12 | Basf Se | Pesticidal Compounds |
| WO2018138050A1 (de) | 2017-01-26 | 2018-08-02 | Bayer Aktiengesellschaft | Kondensierte bicyclische heterocyclen-derivate als schädlingsbekämpfungsmittel |
| TW201833107A (zh) | 2017-02-06 | 2018-09-16 | 德商拜耳廠股份有限公司 | 作為殺蟲劑之經２－（雜）芳基取代的稠合雜環衍生物 |
| AU2018257372B2 (en) | 2017-04-24 | 2022-06-02 | Bayer Aktiengesellschaft | Condensed bicyclic heterocyclic-compound derivatives as pest control agents |
| AR111960A1 (es) | 2017-05-26 | 2019-09-04 | Incyte Corp | Formas cristalinas de un inhibidor de fgfr y procesos para su preparación |
| IL271491B2 (en) | 2017-06-22 | 2023-09-01 | Celgene Corp | Treatment of carcinoma of the liver characterized by hepatitis b virus infection |
| EP3305786A3 (de) | 2018-01-22 | 2018-07-25 | Bayer CropScience Aktiengesellschaft | Kondensierte bicyclische heterocyclen-derivate als schädlingsbekämpfungsmittel |
| CN111741958A (zh) | 2018-02-21 | 2020-10-02 | 拜耳公司 | 作为害虫防治剂的稠合双环杂环衍生物 |
| BR112020020081A2 (pt) | 2018-04-20 | 2021-01-05 | Bayer Aktiengesellschaft | Derivados de heterocicleno como agentes de controle de pragas |
| KR102956194B1 (ko) | 2018-05-04 | 2026-04-23 | 인사이트 코포레이션 | Fgfr 억제제의 염 |
| RS66310B1 (sr) | 2018-05-04 | 2025-01-31 | Incyte Corp | Čvrsti oblici inhibitora fgfr i procesi za njegovu pripremu |
| EP3636645A1 (de) | 2018-10-11 | 2020-04-15 | Bayer Aktiengesellschaft | Verfahren zur herstellung schwefel-substituierter pyridinderivate |
| PH12021552065A1 (en) | 2019-02-26 | 2022-05-23 | Bayer Ag | Condensed bicyclic heterocyclic derivatives as pest control agents |
| CN113710669A (zh) | 2019-02-26 | 2021-11-26 | 拜耳公司 | 作为农药的稠合双环杂环衍生物 |
| WO2020185532A1 (en) | 2019-03-08 | 2020-09-17 | Incyte Corporation | Methods of treating cancer with an fgfr inhibitor |
| AR119140A1 (es) | 2019-06-13 | 2021-11-24 | Pi Industries Ltd | Compuestos heterocíclicos fusionados y su uso como agentes de control de plagas |
| WO2021007269A1 (en) | 2019-07-09 | 2021-01-14 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
| US12122767B2 (en) | 2019-10-01 | 2024-10-22 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
| GEP20247679B (en) | 2019-10-14 | 2024-10-10 | Incyte Corp | Bicyclic heterocycles as fgfr inhibitors |
| US11566028B2 (en) | 2019-10-16 | 2023-01-31 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
| WO2021113479A1 (en) | 2019-12-04 | 2021-06-10 | Incyte Corporation | Tricyclic heterocycles as fgfr inhibitors |
| MX2022006691A (es) | 2019-12-04 | 2022-09-19 | Incyte Corp | Derivados de un inhibidor de receptores del factor de crecimiento de fibroblastos (fgfr). |
| US12012409B2 (en) | 2020-01-15 | 2024-06-18 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
| CN113912608B (zh) * | 2020-07-10 | 2023-07-14 | 江苏恒瑞医药股份有限公司 | 嘧啶并嘧啶酮类衍生物、其制备方法及其在医药上的应用 |
| EP4323405A1 (en) | 2021-04-12 | 2024-02-21 | Incyte Corporation | Combination therapy comprising an fgfr inhibitor and a nectin-4 targeting agent |
| TW202313610A (zh) | 2021-06-09 | 2023-04-01 | 美商英塞特公司 | 作為ｆｇｆｒ抑制劑之三環雜環 |
| CA3220274A1 (en) | 2021-06-09 | 2022-12-15 | Incyte Corporation | Tricyclic heterocycles as fgfr inhibitors |
| WO2025177310A1 (en) | 2024-02-23 | 2025-08-28 | Pi Industries Ltd. | Fused heterocyclic compounds and its uses thereof |
| WO2025177312A1 (en) | 2024-02-23 | 2025-08-28 | Pi Industries Ltd. | Fused heterocyclic compounds and its uses thereof |
Family Cites Families (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5304121A (en) | 1990-12-28 | 1994-04-19 | Boston Scientific Corporation | Drug delivery system making use of a hydrogel polymer coating |
| US5994341A (en) | 1993-07-19 | 1999-11-30 | Angiogenesis Technologies, Inc. | Anti-angiogenic Compositions and methods for the treatment of arthritis |
| US5525711A (en) * | 1994-05-18 | 1996-06-11 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Pteridine nucleotide analogs as fluorescent DNA probes |
| US6099562A (en) | 1996-06-13 | 2000-08-08 | Schneider (Usa) Inc. | Drug coating with topcoat |
| US6875769B2 (en) | 1996-05-23 | 2005-04-05 | Pfizer Inc. | Substituted6,6-hetero-bicyclicderivatives |
| TW477787B (en) | 1996-08-27 | 2002-03-01 | Pfizer | Pyrido six-membered nitrogen-containing cyclic ring derivatives having corticotropin releasing factor antagonist activity and pharmaceutical composition containing same |
| ES2301194T3 (es) * | 1997-02-05 | 2008-06-16 | Warner-Lambert Company Llc | Pirido 2,3-d pirimidinas y 4-aminopirimidinas como inhibidores de la proliferacion celular. |
| SI1028950T1 (en) | 1997-10-28 | 2003-08-31 | Warner-Lambert Company Llc | 7-substituted quinazolin-2,4-diones useful as antibacterial agents |
| WO1999051613A1 (en) | 1998-04-03 | 1999-10-14 | Medivir Ab | Prodrugs of phosphorous-containing pharmaceuticals |
| DE69939168D1 (de) | 1998-05-26 | 2008-09-04 | Warner Lambert Co | Bicyclische pyrimidine und bicyclische 3,4-dihydropyrimidine als inhibitoren der zellvermehrung |
| US20040044012A1 (en) | 1998-05-26 | 2004-03-04 | Dobrusin Ellen Myra | Bicyclic pyrimidines and bicyclic 3,4-dihydropyrimidines as inhibitors of cellular proliferation |
| JP2003509425A (ja) * | 1999-09-15 | 2003-03-11 | ワーナー−ランバート・カンパニー | キナーゼ阻害剤としてのプテリジノン |
| SK10772002A3 (sk) | 2000-01-27 | 2004-01-08 | Warner-Lambert Company | Pyridopyrimidinónové deriváty na liečbu neurodegeneratívnych ochorení |
| GB2359551A (en) * | 2000-02-23 | 2001-08-29 | Astrazeneca Uk Ltd | Pharmaceutically active pyrimidine derivatives |
| AR030053A1 (es) * | 2000-03-02 | 2003-08-13 | Smithkline Beecham Corp | 1h-pirimido [4,5-d] pirimidin-2-onas y sales, composiciones farmaceuticas, uso para la fabricacion de un medicamento y procedimiento para producirlas |
| EP1267876A1 (en) | 2000-03-23 | 2003-01-02 | Merck & Co., Inc. | Thrombin inhibitors |
| DE10050661A1 (de) | 2000-10-13 | 2002-04-18 | Gruenenthal Gmbh | Substituierte 3,4-Dihydro-pyrimido[1,2-a]pyrimidine und 3,4-Dihydro-pyrazino[1,2-a]pyrimidine |
| AU2002246855B2 (en) * | 2000-10-23 | 2005-12-22 | Smithkline Beecham Corporation | Novel compounds |
| WO2002076954A1 (en) * | 2001-03-23 | 2002-10-03 | Smithkline Beecham Corporation | Compounds useful as kinase inhibitors for the treatment of hyperproliferative diseases |
| PE20030008A1 (es) | 2001-06-19 | 2003-01-22 | Bristol Myers Squibb Co | Inhibidores duales de pde 7 y pde 4 |
| US6511867B2 (en) | 2001-06-30 | 2003-01-28 | Ovonyx, Inc. | Utilizing atomic layer deposition for programmable device |
| ATE466581T1 (de) * | 2001-12-07 | 2010-05-15 | Vertex Pharma | Verbindungen auf pyrimidin-basis als gsk-3-hemmer |
| CN1665808A (zh) * | 2002-05-06 | 2005-09-07 | 沃泰克斯药物股份有限公司 | 噻二唑或噁二唑及其作为jak蛋白激酶抑制剂的用途 |
| US7384937B2 (en) | 2002-11-06 | 2008-06-10 | Bristol-Myers Squibb Co. | Fused heterocyclic compounds and use thereof |
| CA2533626A1 (en) | 2003-07-22 | 2005-02-03 | Janssen Pharmaceutica, N.V. | Quinolinone derivatives as inhibitors of c-fms kinase |
| CA2683820A1 (en) * | 2007-04-11 | 2008-10-23 | Exelixis, Inc. | Pyrido [2, 3-d] pyrimidin-7-one compounds as inhibitors of p13k-alpha for the treatment of cancer |
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| AU2005316668B2 (en) | 2012-09-06 |
| AU2005316668A1 (en) | 2006-06-22 |
| WO2006065703A1 (en) | 2006-06-22 |
| JP2008523099A (ja) | 2008-07-03 |
| EP1828186A1 (en) | 2007-09-05 |
| US20060211702A1 (en) | 2006-09-21 |
| JP5111113B2 (ja) | 2012-12-26 |
| US20110059976A1 (en) | 2011-03-10 |
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