CA2669704A1 - Sulfoximines as kinase inhibitors - Google Patents
Sulfoximines as kinase inhibitors Download PDFInfo
- Publication number
- CA2669704A1 CA2669704A1 CA002669704A CA2669704A CA2669704A1 CA 2669704 A1 CA2669704 A1 CA 2669704A1 CA 002669704 A CA002669704 A CA 002669704A CA 2669704 A CA2669704 A CA 2669704A CA 2669704 A1 CA2669704 A1 CA 2669704A1
- Authority
- CA
- Canada
- Prior art keywords
- cr7r8
- methyl
- phenyl
- sulfanylidene
- ethynyl
- 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
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Classifications
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- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
- C07D213/82—Amides; Imides in position 3
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- 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
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- 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
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- C—CHEMISTRY; METALLURGY
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero 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
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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Applications Claiming Priority (3)
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| US86608006P | 2006-11-16 | 2006-11-16 | |
| US60/866,080 | 2006-11-16 | ||
| PCT/US2007/084999 WO2008061236A2 (en) | 2006-11-16 | 2007-11-16 | Sulfoximines as kinase inhibitors |
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| CA2669704A1 true CA2669704A1 (en) | 2008-05-22 |
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| EP (1) | EP2099757B1 (enExample) |
| JP (1) | JP2010510242A (enExample) |
| AU (1) | AU2007319151B2 (enExample) |
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| CA (1) | CA2669704A1 (enExample) |
| WO (1) | WO2008061236A2 (enExample) |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US7456476B2 (en) | 2003-06-27 | 2008-11-25 | Intel Corporation | Nonplanar semiconductor device with partially or fully wrapped around gate electrode and methods of fabrication |
| US8455656B2 (en) | 2004-04-30 | 2013-06-04 | Allergan, Inc. | Kinase inhibitors |
| WO2005107708A1 (en) | 2004-04-30 | 2005-11-17 | Allergan, Inc. | Biodegradable intravitreal tyrosine kinase inhibitors implants |
| US7771742B2 (en) | 2004-04-30 | 2010-08-10 | Allergan, Inc. | Sustained release intraocular implants containing tyrosine kinase inhibitors and related methods |
| US7042009B2 (en) | 2004-06-30 | 2006-05-09 | Intel Corporation | High mobility tri-gate devices and methods of fabrication |
| US20060086977A1 (en) | 2004-10-25 | 2006-04-27 | Uday Shah | Nonplanar device with thinned lower body portion and method of fabrication |
| US7518196B2 (en) | 2005-02-23 | 2009-04-14 | Intel Corporation | Field effect transistor with narrow bandgap source and drain regions and method of fabrication |
| US7858481B2 (en) | 2005-06-15 | 2010-12-28 | Intel Corporation | Method for fabricating transistor with thinned channel |
| US7547637B2 (en) | 2005-06-21 | 2009-06-16 | Intel Corporation | Methods for patterning a semiconductor film |
| US7279375B2 (en) * | 2005-06-30 | 2007-10-09 | Intel Corporation | Block contact architectures for nanoscale channel transistors |
| US20070090416A1 (en) | 2005-09-28 | 2007-04-26 | Doyle Brian S | CMOS devices with a single work function gate electrode and method of fabrication |
| US7485503B2 (en) | 2005-11-30 | 2009-02-03 | Intel Corporation | Dielectric interface for group III-V semiconductor device |
| WO2007087419A2 (en) | 2006-01-24 | 2007-08-02 | Allergan, Inc. | Substituted 3-(5-membered unsaturated heterocyclyl) -1, 3-dihydro-indol-2-one derivatives as tyrosine kinase inhibitors for the treatment of cancer |
| US8143646B2 (en) | 2006-08-02 | 2012-03-27 | Intel Corporation | Stacking fault and twin blocking barrier for integrating III-V on Si |
| US8558002B2 (en) * | 2006-11-16 | 2013-10-15 | Allergan, Inc. | Sulfoximines as kinase inhibitors |
| US8143410B2 (en) * | 2006-11-16 | 2012-03-27 | Allergan, Inc. | Kinase inhibitors |
| US8642067B2 (en) * | 2007-04-02 | 2014-02-04 | Allergen, Inc. | Methods and compositions for intraocular administration to treat ocular conditions |
| US8362566B2 (en) | 2008-06-23 | 2013-01-29 | Intel Corporation | Stress in trigate devices using complimentary gate fill materials |
| AR076332A1 (es) * | 2009-04-21 | 2011-06-01 | Boehringer Ingelheim Int | Derivados heterociclicos de 5-alquinil-piridinas, composiciones farmaceuticas que los comprenden y uso de los mismos para el tratamiento y/o prevencion del cancer, procesos inflamatorios, autoinmunes, y/o infecciones. |
| US20100278897A1 (en) * | 2009-05-01 | 2010-11-04 | Allergan, Inc. | Intraocular bioactive agent delivery system with molecular partitioning system |
| KR20160096174A (ko) * | 2013-12-12 | 2016-08-12 | 알러간, 인코포레이티드 | 키나제 저해제로서의 치환된 다이알킬(옥사이도)-λ⁴-설판일리덴 니코틴아마이드 유도체 |
| CN105814021B (zh) * | 2013-12-12 | 2020-03-13 | 阿勒根公司 | 作为激酶抑制剂的取代的烟酰胺衍生物 |
| CN111662227B (zh) * | 2019-03-06 | 2022-07-05 | 中国科学院上海药物研究所 | 邻氨基吡啶炔类化合物及其制备方法和用途 |
Family Cites Families (50)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2383874A (en) * | 1941-04-24 | 1945-08-28 | Swiss Firm Of J R Geigy A G | p-aminobenzenesulphonamides and a process for their manufacture |
| GB602558A (en) * | 1945-10-24 | 1948-05-28 | Geigy Ag J R | Manufacture of aromatic acyl-sulphonamides |
| DE821977C (de) * | 1949-10-02 | 1951-11-22 | Basf Ag | Verfahren zur Herstellung von Azofarbstoffen |
| ZA804076B (en) * | 1979-07-18 | 1981-06-24 | Ici Ltd | Herbicides |
| EP0075377A3 (en) * | 1979-07-18 | 1983-08-31 | Imperial Chemical Industries Plc | Diphenyl ether compounds, their use as herbicides, and herbicidal compositions containing them |
| GB2061914A (en) * | 1979-11-01 | 1981-05-20 | American Cyanamid Co | Substituted anilines and their use as anti-atherosclerotic agents |
| JPS5998056A (ja) * | 1982-11-04 | 1984-06-06 | エフ・ホフマン−ラ・ロシユ・ウント・コンパニ−・アクチエンゲゼルシヤフト | 除草活性を有する安息香酸誘導体 |
| EP0109575A3 (de) | 1982-11-04 | 1984-09-05 | F. HOFFMANN-LA ROCHE & CO. Aktiengesellschaft | Benzoesäurederivate, Verfahren und Mittel zu deren Herstellung |
| JPS5890555A (ja) * | 1982-11-22 | 1983-05-30 | Ishihara Sangyo Kaisha Ltd | ベンズアミド誘導体及びそれらを含有する除草剤 |
| JPS6216465A (ja) * | 1985-03-14 | 1987-01-24 | Nissan Chem Ind Ltd | ベンズアミド誘導体、その製法および土壌病害防除剤 |
| US4966849A (en) | 1985-09-20 | 1990-10-30 | President And Fellows Of Harvard College | CDNA and genes for human angiogenin (angiogenesis factor) and methods of expression |
| DE3867401D1 (de) * | 1987-03-18 | 1992-02-13 | American Home Prod | Sulfonylcarboxamide. |
| US4826990A (en) * | 1987-09-30 | 1989-05-02 | American Home Products Corporation | 2-aryl substituted heterocyclic compounds as antiallergic and antiinflammatory agents |
| US5217999A (en) | 1987-12-24 | 1993-06-08 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Styryl compounds which inhibit EGF receptor protein tyrosine kinase |
| ES2064101T3 (es) | 1990-04-02 | 1995-01-16 | Pfizer | Compuestos de acido bencilfosfonico inhibidores de la quinasa de tirosina. |
| US5302606A (en) | 1990-04-16 | 1994-04-12 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Styryl-substituted pyridyl compounds which inhibit EGF receptor tyrosine kinase |
| WO1992020642A1 (en) | 1991-05-10 | 1992-11-26 | Rhone-Poulenc Rorer International (Holdings) Inc. | Bis mono-and bicyclic aryl and heteroaryl compounds which inhibit egf and/or pdgf receptor tyrosine kinase |
| CA2068355A1 (en) * | 1991-05-14 | 1992-11-15 | Mark S. Chambers | Benzodiazephine derivatives, compositions containing them and their use in therapy |
| JPH06503095A (ja) | 1991-05-29 | 1994-04-07 | ファイザー・インコーポレーテッド | 三環式ポリヒドロキシ系のチロシンキナーゼ阻害薬 |
| JP2600644B2 (ja) * | 1991-08-16 | 1997-04-16 | 藤沢薬品工業株式会社 | チアゾリルベンゾフラン誘導体 |
| JPH05294930A (ja) * | 1992-04-21 | 1993-11-09 | Yoshitomi Pharmaceut Ind Ltd | スチリル化合物 |
| JPH08503450A (ja) | 1992-08-06 | 1996-04-16 | ワーナー−ランバート・コンパニー | 蛋白チロシンキナーゼを阻害し、かつ抗腫瘍特性を有する2−チオインドール(セレノインドール)および関連ジスルフィド(セレニド) |
| US5330992A (en) | 1992-10-23 | 1994-07-19 | Sterling Winthrop Inc. | 1-cyclopropyl-4-pyridyl-quinolinones |
| AU687727B2 (en) | 1992-10-28 | 1998-03-05 | Genentech Inc. | Vascular endothelial cell growth factor antagonists |
| GB9226855D0 (en) | 1992-12-23 | 1993-02-17 | Erba Carlo Spa | Vinylene-azaindole derivatives and process for their preparation |
| DE4410453A1 (de) * | 1994-03-25 | 1995-09-28 | Hoechst Ag | Substituierte heterocyclische Carbonsäureamidester, ihre Herstellung und ihre Verwendung als Arzneimittel |
| EP0807105B1 (en) * | 1994-10-27 | 2004-06-16 | Fujisawa Pharmaceutical Co., Ltd. | Pyridopyrimidones, quinolines and fused n-heretocycles as bradykinin antagonists |
| US5880141A (en) | 1995-06-07 | 1999-03-09 | Sugen, Inc. | Benzylidene-Z-indoline compounds for the treatment of disease |
| IL124969A (en) * | 1995-12-28 | 2002-09-12 | Fujisawa Pharmaceutical Co | History of benzimidazole, processes for their preparation and pharmaceutical preparations containing them |
| WO1998056757A1 (fr) * | 1997-06-11 | 1998-12-17 | Sankyo Company, Limited | Derives de benzylamine |
| DE69926148D1 (en) | 1998-11-09 | 2005-08-18 | Black James Foundation | Gastrin und cholecystokinin rezeptor ligande |
| MXPA02009313A (es) * | 2000-03-22 | 2005-04-19 | Bayer Cropscience Gmbh | Acilsulfimidas heterociclicas, un metodo para su produccion, agentes que contienen las mismas y su uso como plaguicidas. |
| DE10021246A1 (de) * | 2000-04-25 | 2001-10-31 | Schering Ag | Substituierte Benzoesäureamide und deren Verwendung als Arzneimittel |
| US20020054093A1 (en) | 2000-10-04 | 2002-05-09 | Gonzalez Emmanuel C. | Ergonomic graphic interface for webpages, internet browsers and computers |
| JP2002205464A (ja) * | 2000-11-10 | 2002-07-23 | Oji Paper Co Ltd | 感熱記録体 |
| ES2257461T3 (es) * | 2000-12-21 | 2006-08-01 | Bristol-Myers Squibb Company | Inhibidores de tiazolilo de tirosina quinasas de la familia tec. |
| WO2004014300A2 (en) * | 2002-08-09 | 2004-02-19 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
| DE10349423A1 (de) * | 2003-10-16 | 2005-06-16 | Schering Ag | Sulfoximinsubstituierte Parimidine als CDK- und/oder VEGF-Inhibitoren, deren Herstellung und Verwendung als Arzneimittel |
| WO2005108370A1 (ja) * | 2004-04-16 | 2005-11-17 | Ajinomoto Co., Inc. | ベンゼン化合物 |
| DE102004031323A1 (de) * | 2004-06-29 | 2006-01-19 | Bayer Cropscience Ag | Substituierte Pyridazincarboxamide und Derivate hiervon |
| WO2006013449A1 (en) | 2004-07-30 | 2006-02-09 | Adriaan Francois Roberts | A swimming pool installation and accessory |
| US7776869B2 (en) | 2004-10-18 | 2010-08-17 | Amgen Inc. | Heteroaryl-substituted alkyne compounds and method of use |
| US20100048543A1 (en) | 2005-02-01 | 2010-02-25 | Astrazeneca Ab | Pyrimidine compounds having ties (tek) inhibitory activity |
| GB0502418D0 (en) | 2005-02-05 | 2005-03-16 | Astrazeneca Ab | Compounds |
| JP5081807B2 (ja) * | 2005-03-16 | 2012-11-28 | 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 | 補体−媒介疾患及び状態の処置のための新規なチオフェンスルホキシイミン |
| EP1705177A1 (en) * | 2005-03-23 | 2006-09-27 | Schering Aktiengesellschaft | N-aryl-sulfoximine-substituted pyrimidines as CDK- and/or VEGF inhibitors, their production and use as pharmaceutical agents |
| US20080194552A1 (en) * | 2005-03-31 | 2008-08-14 | Astrazeneca Ab | Aminopyrimidine Derivatives With Tie2 Inhibiting Activity |
| ES2761180T3 (es) | 2005-12-23 | 2020-05-19 | Ariad Pharma Inc | Compuestos bicíclicos de heteroarilo |
| DE102006041382A1 (de) * | 2006-08-29 | 2008-03-20 | Bayer Schering Pharma Ag | Carbamoyl-Sulfoximide als Proteinkinaseinhibitoren |
| TW200930369A (en) * | 2007-11-15 | 2009-07-16 | Astrazeneca Ab | Bis-(sulfonylamino) derivatives in therapy |
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Also Published As
| Publication number | Publication date |
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| EP2099757A2 (en) | 2009-09-16 |
| JP2010510242A (ja) | 2010-04-02 |
| HK1134674A1 (en) | 2010-05-07 |
| BRPI0718895A2 (pt) | 2013-12-10 |
| WO2008061236A3 (en) | 2008-07-31 |
| US7915443B2 (en) | 2011-03-29 |
| US20090099181A1 (en) | 2009-04-16 |
| AU2007319151B2 (en) | 2013-05-23 |
| AU2007319151A1 (en) | 2008-05-22 |
| EP2099757B1 (en) | 2014-06-25 |
| WO2008061236A2 (en) | 2008-05-22 |
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| FZDE | Discontinued |
Effective date: 20150812 |