OA11833A - Heteroaryl-substituted quinolin-2-one derivatives useful as anticancer agents. - Google Patents
Heteroaryl-substituted quinolin-2-one derivatives useful as anticancer agents. Download PDFInfo
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- OA11833A OA11833A OA1200100212A OA1200100212A OA11833A OA 11833 A OA11833 A OA 11833A OA 1200100212 A OA1200100212 A OA 1200100212A OA 1200100212 A OA1200100212 A OA 1200100212A OA 11833 A OA11833 A OA 11833A
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- OAPI
- Prior art keywords
- methyl
- chloro
- phenyl
- cr13r14
- formula
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- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical class C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 title description 18
- 239000002246 antineoplastic agent Substances 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 317
- 238000000034 method Methods 0.000 claims abstract description 113
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- 241000124008 Mammalia Species 0.000 claims abstract description 22
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- 230000002194 synthesizing effect Effects 0.000 claims abstract description 9
- -1 hydroxy, amino Chemical group 0.000 claims description 128
- 125000003118 aryl group Chemical group 0.000 claims description 109
- 125000001424 substituent group Chemical group 0.000 claims description 78
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 67
- 125000000217 alkyl group Chemical group 0.000 claims description 61
- 229910052739 hydrogen Inorganic materials 0.000 claims description 51
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 50
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 50
- 229910052799 carbon Inorganic materials 0.000 claims description 47
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 38
- 239000000203 mixture Substances 0.000 claims description 38
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 37
- 125000004122 cyclic group Chemical group 0.000 claims description 29
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 27
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- 125000003342 alkenyl group Chemical group 0.000 claims description 24
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
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- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 8
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
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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
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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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
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- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oncology (AREA)
- Urology & Nephrology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Communicable Diseases (AREA)
- Hematology (AREA)
- Vascular Medicine (AREA)
- Virology (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US11970299P | 1999-02-11 | 1999-02-11 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| OA11833A true OA11833A (en) | 2005-08-23 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| OA1200100212A OA11833A (en) | 1999-02-11 | 2000-02-04 | Heteroaryl-substituted quinolin-2-one derivatives useful as anticancer agents. |
Country Status (39)
| Country | Link |
|---|---|
| US (3) | US6258824B1 (fr) |
| EP (1) | EP1150973B1 (fr) |
| JP (3) | JP4090200B2 (fr) |
| KR (1) | KR20010102073A (fr) |
| CN (1) | CN1340051A (fr) |
| AP (1) | AP2001002241A0 (fr) |
| AR (1) | AR028985A1 (fr) |
| AT (1) | ATE297916T1 (fr) |
| AU (1) | AU2124800A (fr) |
| BG (1) | BG105860A (fr) |
| BR (1) | BR0008202A (fr) |
| CA (1) | CA2362394C (fr) |
| CO (1) | CO5140097A1 (fr) |
| CZ (1) | CZ20012910A3 (fr) |
| DE (1) | DE60020812T2 (fr) |
| DZ (1) | DZ3009A1 (fr) |
| EA (1) | EA200100766A1 (fr) |
| EE (1) | EE200100425A (fr) |
| ES (1) | ES2243228T3 (fr) |
| GT (1) | GT200000014A (fr) |
| HK (1) | HK1042096A1 (fr) |
| HN (1) | HN2000000019A (fr) |
| HR (1) | HRP20010574A2 (fr) |
| HU (1) | HUP0105231A3 (fr) |
| ID (1) | ID29584A (fr) |
| IL (1) | IL144307A0 (fr) |
| IS (1) | IS5997A (fr) |
| MA (1) | MA26718A1 (fr) |
| NO (1) | NO20013909L (fr) |
| OA (1) | OA11833A (fr) |
| PA (1) | PA8490601A1 (fr) |
| PE (1) | PE20001464A1 (fr) |
| PL (1) | PL349839A1 (fr) |
| SK (1) | SK11002001A3 (fr) |
| SV (1) | SV2001000020A (fr) |
| TN (1) | TNSN00028A1 (fr) |
| TR (2) | TR200201296T2 (fr) |
| WO (1) | WO2000047574A1 (fr) |
| ZA (1) | ZA200106520B (fr) |
Families Citing this family (92)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ID26987A (id) * | 1998-07-06 | 2001-02-22 | Janssen Pharmaceutica Nv | Inhibitor-inhibitor transferase protein farnesil dengan sifat-sifat peka terhadap sinar radiasi in vivo |
| TR200201296T2 (tr) * | 1999-02-11 | 2002-07-22 | Pfizer Products Inc. | Antikanser maddeleri olarak faydalı heteroaril-ikame edilmiş kinolin-2-on türevleri |
| AU781986B2 (en) * | 1999-11-05 | 2005-06-23 | Cytovia, Inc. | Substituted 4H-chromene and analogs as activators of caspases and inducers of apoptosis and the use thereof |
| ES2212971T3 (es) * | 1999-11-30 | 2004-08-16 | Pfizer Products Inc. | Derivados de quinolina utiles para la inhibicion de la farnesil protein transferasa. |
| HN2000000266A (es) * | 2000-01-21 | 2001-05-21 | Pfizer Prod Inc | Compuesto anticanceroso y metodo de separacion de enantiomeros util para sintetizar dicho compuesto. |
| EP1253921A4 (fr) * | 2000-01-28 | 2004-10-13 | Merck & Co Inc | Traitement ou prevention du cancer de la prostate avec un medicament inhibiteur selectif de cox-2 |
| JO2361B1 (en) * | 2000-06-22 | 2006-12-12 | جانسين فارماسيوتيكا ان. في | Enaniumer 1,2-anylated quinoline inhibitor for the transporter - farnesyl |
| EP1170011A1 (fr) * | 2000-07-06 | 2002-01-09 | Boehringer Ingelheim International GmbH | Nouvelle utilisation des inhibiteurs de facteur de croissance épidermique |
| JP4974439B2 (ja) * | 2000-09-25 | 2012-07-11 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | ファルネシルトランスフェラーゼを阻害する６−ヘテロシクリルメチルキノリノン誘導体 |
| ATE409189T1 (de) * | 2000-09-25 | 2008-10-15 | Janssen Pharmaceutica Nv | Farnesyl transferase-hemmende 6- heterocyclylmethyl-chinolin und chinazol-derivate |
| US7053105B2 (en) | 2000-09-25 | 2006-05-30 | Janssen Pharmaceutica, N.V. | Farnesyl transferase inhibiting quinoline and quinazoline derivatives as farnesyl transferase inhibitors |
| WO2002024683A1 (fr) | 2000-09-25 | 2002-03-28 | Janssen Pharmaceutica N.V. | Derives de la quinoleine et de la quinazoline 6-[(phenyle substitue)methyle] inhibiteurs de la farnesyle transferase |
| CN1703403A (zh) * | 2000-10-02 | 2005-11-30 | 詹森药业有限公司 | 趋代谢的谷氨酸盐受体拮抗剂 |
| ES2328225T3 (es) | 2000-11-21 | 2009-11-11 | Janssen Pharmaceutica Nv | Derivados benzoheterociclicos inhibidores de la farnesil-transferasa. |
| EP1351954B1 (fr) * | 2000-12-27 | 2006-05-03 | Janssen Pharmaceutica N.V. | Derives de 4-heterocyclyl-quinoline et quinazoline inhibant lafarnesyl-transferase |
| ATE319704T1 (de) | 2000-12-27 | 2006-03-15 | Janssen Pharmaceutica Nv | Farnesyltransferase hemmende, in der 4-stellung substituierte chinolin- und chinazolinderivate |
| US6858607B1 (en) | 2001-05-16 | 2005-02-22 | Cytovia, Inc. | 7,8-fused 4H-chromene and analogs as activators of caspases and inducers of apoptosis and the use thereof |
| EP1392283A4 (fr) | 2001-05-16 | 2004-10-20 | Cytovia Inc | Coumarines et quinolines substituees utilisees comme activateurs des caspases |
| EP1392683B1 (fr) * | 2001-05-16 | 2009-12-02 | Cytovia, Inc. | 4h-chromènes substitués et analogues en tant qu'activateurs de caspases et inducteurs d'apoptose, et leur utilisation comme agents anticancéreux |
| WO2003006006A1 (fr) * | 2001-07-09 | 2003-01-23 | The Regents Of The University Of California | Utilisation d'inhibiteurs de metalloproteinases matricielles pour limiter les atteintes nerveuses |
| CA2469275C (fr) | 2001-12-19 | 2011-09-06 | Janssen Pharmaceutica N.V. | Utilisation de derives de quinoline 1,8-anneles substitues avec des triazoles lies par le carbone en tant qu'inhibiteurs de farnesyl transferase |
| ES2287466T3 (es) | 2002-03-22 | 2007-12-16 | Janssen Pharmaceutica N.V. | Derivados de 2-quinolinona y quinazolina de bencilimidazolil sustituidas como inhibidores de la farnesil transferasa. |
| NZ535438A (en) * | 2002-03-29 | 2006-08-31 | Janssen Pharmaceutica Nv | Radiolabelled quinoline and quinolinone derivatives and their use as metabotropic glutamate receptor ligands |
| CA2481480C (fr) | 2002-04-15 | 2011-04-12 | Janssen Pharmaceutica N.V. | Derives de quinazoline tricylique inhibant la farnesyl transferase substitues avec des imidazoles ou des triazoles a liaison carbone |
| US7476741B2 (en) | 2002-05-16 | 2009-01-13 | Cytovia, Inc. | Substituted 4H-chromens, 2H-chromenes, chromans and analogs as activators of caspases and inducers of apoptosis and the use thereof |
| CN100349887C (zh) | 2002-05-16 | 2007-11-21 | 西托维亚公司 | 取代的4－芳基－4h－吡咯并[2,3－h]色烯和类似物及其药物组合物和用途 |
| US20040186160A1 (en) * | 2002-12-13 | 2004-09-23 | Sugen, Inc. | Hexahydro-cyclohepta-pyrrole oxindole as potent kinase inhibitors |
| AU2003286321A1 (en) * | 2002-12-19 | 2004-07-14 | Pfizer Inc. | 2-(1h-indazol-6-ylamino)-benzamide compounds as protein kinases inhibitors useful for the treatment of ophtalmic diseases |
| PT2476667E (pt) | 2003-02-26 | 2014-09-18 | Sugen Inc | Compostos de aminoheteroarilo como inibidores da proteína quinase |
| WO2004076446A1 (fr) * | 2003-02-27 | 2004-09-10 | Chugai Seiyaku Kabushiki Kaisha | Derive de benzothiophene |
| CA2533626A1 (fr) * | 2003-07-22 | 2005-02-03 | Janssen Pharmaceutica, N.V. | Derives de quinolinone en tant qu'inhibiteurs de c-fms kinase |
| JP4691041B2 (ja) | 2003-11-20 | 2011-06-01 | チルドレンズ ホスピタル メディカル センター | Ｇｔｐアーゼ阻害剤および使用方法 |
| CA2559221A1 (fr) * | 2004-03-18 | 2005-09-29 | Brigham And Women's Hospital, Inc. | Procedes pour le traitement de synucleinopathies |
| US20050288298A1 (en) * | 2004-03-18 | 2005-12-29 | The Brigham And Women's Hospital, Inc. | Methods for the treatment of synucleinopathies |
| WO2005089515A2 (fr) * | 2004-03-18 | 2005-09-29 | The Brigham And Women's Hospital, Inc. | Procedes de traitement des synucleinopathies |
| CA2559285A1 (fr) * | 2004-03-18 | 2005-09-29 | Brigham And Women's Hospital, Inc. | Traitement des synucleinopathies |
| US20070293539A1 (en) * | 2004-03-18 | 2007-12-20 | Lansbury Peter T | Methods for the treatment of synucleinopathies |
| BRPI0509580A (pt) * | 2004-03-30 | 2007-11-27 | Pfizer Prod Inc | combinações de inibidores de transdução de sinal |
| JP4242911B2 (ja) | 2004-08-26 | 2009-03-25 | ファイザー・インク | プロテインキナーゼ阻害薬としてのエナンチオピュアなアミノヘテロアリール化合物 |
| EP1786777A1 (fr) * | 2004-08-26 | 2007-05-23 | Pfizer, Inc. | Composes aminoheteroaryles en tant qu'inhibiteurs des proteines tyrosine kinases |
| CA2577937C (fr) * | 2004-08-26 | 2010-12-21 | Pfizer Inc. | Composes aminoheteroaryle a substitution pyrazole servant d'inhibiteurs de proteine kinase |
| WO2006041900A2 (fr) * | 2004-10-07 | 2006-04-20 | Cytovia, Inc. | N-aryl-1h-pyrazolo[3,4-b]quinolin-4-amines substitues et analogues utilises comme activateurs de caspases et inducteurs de l'apoptose |
| WO2007016539A2 (fr) | 2005-07-29 | 2007-02-08 | Children's Hospital Medical Center | Inhibiteurs de gtpase et methodes d'utilisation et structure cristalline de la gtpase rac-1 |
| SI2447283T1 (sl) | 2005-09-07 | 2015-12-31 | Amgen Fremont Inc. | Človeška monoklonska protitelesa proti aktivin receptorski kinazi-1 (ALK-1) |
| AU2006292278B2 (en) | 2005-09-20 | 2012-03-08 | Osi Pharmaceuticals, Inc. | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors |
| AU2006331542A1 (en) | 2005-12-23 | 2007-07-05 | Link Medicine Corporation | Treatment of synucleinopathies |
| TW200812615A (en) | 2006-03-22 | 2008-03-16 | Hoffmann La Roche | Tumor therapy with an antibody for vascular endothelial growth factor and an antibody for human epithelial growth factor receptor type 2 |
| EA200802058A1 (ru) | 2006-05-09 | 2009-06-30 | Пфайзер Продактс Инк. | Производные циклоалкиламинокислот и их фармацевтические композиции |
| AU2007287794B2 (en) | 2006-08-21 | 2013-03-28 | F. Hoffmann-La Roche Ag | Tumor therapy with an anti-VEGF antibody |
| RU2472788C9 (ru) * | 2007-05-23 | 2013-04-20 | Аллерган, Инк. | (бициклогетероарил)имидазолил)метилгетероарильные соединения как агонисты адренергических рецепторов |
| PL2155733T3 (pl) * | 2007-05-23 | 2013-02-28 | Allergan Inc | Cykliczne laktamy do leczenia jaskry lub podwyższonego ciśnienia śródgałkowego |
| US8129356B2 (en) * | 2007-10-01 | 2012-03-06 | Vanderbilt University | Bmx mediated signal transduction in irradiated vascular endothelium |
| WO2009151683A2 (fr) * | 2008-03-12 | 2009-12-17 | Link Medicine Corporation | Inhibiteurs de quinolinone farnésyl transférase pour le traitement de synucléinopathies et d'autres indications |
| DE102008022221A1 (de) * | 2008-05-06 | 2009-11-12 | Universität des Saarlandes | Inhibitoren der humanen Aldosteronsynthase CYP11B2 |
| AU2009313927A1 (en) * | 2008-11-13 | 2010-05-20 | Astrazeneca Ab | Azaquinolinone derivatives and uses thereof |
| US20100331363A1 (en) * | 2008-11-13 | 2010-12-30 | Link Medicine Corporation | Treatment of mitochondrial disorders using a farnesyl transferase inhibitor |
| US20110060005A1 (en) * | 2008-11-13 | 2011-03-10 | Link Medicine Corporation | Treatment of mitochondrial disorders using a farnesyl transferase inhibitor |
| SG172857A1 (en) * | 2009-02-09 | 2011-08-29 | Supergen Inc | Pyrrolopyrimidinyl axl kinase inhibitors |
| US20120189641A1 (en) | 2009-02-25 | 2012-07-26 | OSI Pharmaceuticals, LLC | Combination anti-cancer therapy |
| US20110171124A1 (en) | 2009-02-26 | 2011-07-14 | Osi Pharmaceuticals, Inc. | In situ methods for monitoring the EMT status of tumor cells in vivo |
| US8642834B2 (en) | 2009-02-27 | 2014-02-04 | OSI Pharmaceuticals, LLC | Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation |
| JP2012519282A (ja) | 2009-02-27 | 2012-08-23 | オーエスアイ・ファーマシューティカルズ，エルエルシー | 間葉様腫瘍細胞またはその生成を阻害する薬剤を同定するための方法 |
| WO2010098866A1 (fr) | 2009-02-27 | 2010-09-02 | Supergen, Inc. | Inhibiteurs cyclopentathiophène/cyclohexathiophène de l'adn méthyltransférase |
| WO2010099138A2 (fr) | 2009-02-27 | 2010-09-02 | Osi Pharmaceuticals, Inc. | Procédés pour l'identification d'agents qui inhibent les cellules tumorales de type mésenchymateuses ou leur formation |
| AU2011223655A1 (en) | 2010-03-03 | 2012-06-28 | OSI Pharmaceuticals, LLC | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors |
| AU2011223643A1 (en) | 2010-03-03 | 2012-06-28 | OSI Pharmaceuticals, LLC | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors |
| WO2012116040A1 (fr) | 2011-02-22 | 2012-08-30 | OSI Pharmaceuticals, LLC | Marqueurs biologiques prédictifs d'une réponse anticancéreuse aux inhibiteurs de la kinase du récepteur du facteur de croissance 1 analogue à l'insuline dans le carcinome hépatocellulaire |
| JP2014519813A (ja) | 2011-04-25 | 2014-08-21 | オーエスアイ・ファーマシューティカルズ，エルエルシー | 癌薬剤発見、診断、および治療におけるｅｍｔ遺伝子シグネチャーの使用 |
| DK2734205T3 (en) | 2011-07-21 | 2018-06-14 | Tolero Pharmaceuticals Inc | Heterocyclic Protein Kinase Inhibitors |
| WO2013152252A1 (fr) | 2012-04-06 | 2013-10-10 | OSI Pharmaceuticals, LLC | Polythérapie antinéoplasique |
| US9980942B2 (en) | 2012-05-02 | 2018-05-29 | Children's Hospital Medical Center | Rejuvenation of precursor cells |
| MY189505A (en) | 2012-10-16 | 2022-02-16 | Janssen Pharmaceutica Nv | Methylene linked quinolinyl modulators of roryt |
| WO2014062655A1 (fr) | 2012-10-16 | 2014-04-24 | Janssen Pharmaceutica Nv | Modulateurs de roryt de type quinolinyle à liaison hétéroaryle |
| HK1213887A1 (zh) | 2012-10-16 | 2016-07-15 | Janssen Pharmaceutica N.V. | RORγt的苯基连接的喹啉基调节剂 |
| US9260426B2 (en) | 2012-12-14 | 2016-02-16 | Arrien Pharmaceuticals Llc | Substituted 1H-pyrrolo [2, 3-b] pyridine and 1H-pyrazolo [3, 4-b] pyridine derivatives as salt inducible kinase 2 (SIK2) inhibitors |
| AR094403A1 (es) | 2013-01-11 | 2015-07-29 | Hoffmann La Roche | Terapia de combinación de anticuerpos anti-her3 |
| PT2970205T (pt) | 2013-03-14 | 2019-08-26 | Tolero Pharmaceuticals Inc | Inibidores da jak2 e da alk2 e métodos para a sua utilização |
| US9206188B2 (en) | 2013-04-18 | 2015-12-08 | Arrien Pharmaceuticals Llc | Substituted pyrrolo[2,3-b]pyridines as ITK and JAK inhibitors |
| US9284308B2 (en) | 2013-10-15 | 2016-03-15 | Janssen Pharmaceutica Nv | Methylene linked quinolinyl modulators of RORγt |
| US9221804B2 (en) | 2013-10-15 | 2015-12-29 | Janssen Pharmaceutica Nv | Secondary alcohol quinolinyl modulators of RORγt |
| US10555941B2 (en) | 2013-10-15 | 2020-02-11 | Janssen Pharmaceutica Nv | Alkyl linked quinolinyl modulators of RORγt |
| CA2926339A1 (fr) | 2013-10-15 | 2015-04-23 | Janssen Pharmaceutica Nv | Modulateurs quinolinyl a liaison alkyle de roryt |
| CA2927182A1 (fr) | 2013-10-15 | 2015-04-23 | Janssen Pharmaceutica Nv | Modulateurs quinolinyl de ror.gamma.t |
| US9403816B2 (en) | 2013-10-15 | 2016-08-02 | Janssen Pharmaceutica Nv | Phenyl linked quinolinyl modulators of RORγt |
| US9328095B2 (en) | 2013-10-15 | 2016-05-03 | Janssen Pharmaceutica Nv | Heteroaryl linked quinolinyl modulators of RORgammat |
| US10028503B2 (en) | 2014-06-18 | 2018-07-24 | Children's Hospital Medical Center | Platelet storage methods and compositions for same |
| WO2017096165A1 (fr) | 2015-12-03 | 2017-06-08 | Agios Pharmaceuticals, Inc. | Inhibiteurs de mat2a pour le traitement du cancer n'exprimant pas mtap |
| CN108003150A (zh) * | 2016-10-31 | 2018-05-08 | 河南工业大学 | 4-杂芳基喹啉酮衍生物的制备方法及其应用 |
| KR20210038906A (ko) | 2018-07-26 | 2021-04-08 | 스미토모 다이니폰 파마 온콜로지, 인크. | 비정상적 acvr1 발현과 연관된 질환을 치료하는 방법 및 그에 사용하기 위한 acvr1 억제제 |
| HUE072069T2 (hu) | 2019-02-12 | 2025-10-28 | Sumitomo Pharma America Inc | 2-((1R,4R)-4-((3-(3-(trifluormetil)fenil)imidazo[1,2- b]piridazin-6-il)amino)ciklohexil)propán-2-ol sósavas sójának kristályos formája |
| CN114450027A (zh) | 2019-08-16 | 2022-05-06 | 儿童医院医疗中心 | 用cdc42特异性抑制剂治疗受试者的方法 |
| WO2021155006A1 (fr) | 2020-01-31 | 2021-08-05 | Les Laboratoires Servier Sas | Inhibiteurs de kinases dépendantes des cyclines et leurs utilisations |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2732531A1 (de) * | 1977-07-19 | 1979-02-01 | Hoechst Ag | Imidazolcarbonsaeuren und deren derivate |
| US4835154A (en) * | 1987-06-01 | 1989-05-30 | Smithkline Beckman Corporation | 1-aralykyl-5-piperazinylmethyl-2-mercaptoimidazoles and 2-alkylthioimidazoles and their use as dopamine-βhydroxylase inhibitors |
| US5136085A (en) * | 1990-11-28 | 1992-08-04 | Glaxo Inc. | Synthesis of 2-aminobenzophenones |
| US5053543A (en) * | 1990-11-28 | 1991-10-01 | Glaxo Inc. | Synthesis of 2-aminobenzophenones |
| TW349948B (en) | 1995-10-31 | 1999-01-11 | Janssen Pharmaceutica Nv | Farnesyl transferase inhibiting 2-quinolone derivatives |
| DE69635966T2 (de) * | 1995-12-08 | 2006-11-30 | Janssen Pharmaceutica N.V. | (Imidazol-5-yl)Methyl-2-Chinolinonderivate als Farnesyl Protein transferase Inhibitoren |
| IL133212A (en) * | 1997-06-02 | 2005-12-18 | Janssen Pharmaceutica Nv | History of use (imidazolil-5-yl) methyl-2-quinolinone that act as culture inhibitors of smooth muscle cells |
| KR20010072991A (ko) | 1998-08-27 | 2001-07-31 | 실버스타인 아써 에이. | 항암제로서 유용한 알키닐-치환된 퀴놀린-2-온 유도체 |
| TR200201296T2 (tr) * | 1999-02-11 | 2002-07-22 | Pfizer Products Inc. | Antikanser maddeleri olarak faydalı heteroaril-ikame edilmiş kinolin-2-on türevleri |
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