NO333771B1 - Metoder for behandling eller forebygging av autiommune sykdommer med 2,4-pyrimidindiaminforbindelser - Google Patents
Metoder for behandling eller forebygging av autiommune sykdommer med 2,4-pyrimidindiaminforbindelser Download PDFInfo
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- NO333771B1 NO333771B1 NO20060992A NO20060992A NO333771B1 NO 333771 B1 NO333771 B1 NO 333771B1 NO 20060992 A NO20060992 A NO 20060992A NO 20060992 A NO20060992 A NO 20060992A NO 333771 B1 NO333771 B1 NO 333771B1
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- cells
- pyrimidinediamine
- compounds
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Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/538—1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with carbocyclic ring systems
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- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/541—Non-condensed thiazines containing further heterocyclic rings
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- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- 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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- 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
- C07D403/14—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 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
- C07D405/12—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 chain containing hetero atoms as chain links
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- 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
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- 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
- C07D413/12—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 chain containing hetero atoms as chain links
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- 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
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
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- 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
- C07D417/12—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 chain containing hetero atoms as chain links
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- 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
- C07D417/14—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 three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/06—Peri-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
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- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Chemical Kinetics & Catalysis (AREA)
- Physical Education & Sports Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Immunology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
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PCT/US2004/024716 WO2005016893A2 (en) | 2003-07-30 | 2004-07-30 | 2,4-pyrimidinediamine compounds for use in the treatment or prevention of autoimmune diseases |
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Families Citing this family (180)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
TWI329105B (en) | 2002-02-01 | 2010-08-21 | Rigel Pharmaceuticals Inc | 2,4-pyrimidinediamine compounds and their uses |
CN103169708B (zh) * | 2002-07-29 | 2018-02-02 | 里格尔药品股份有限公司 | 用2,4‑嘧啶二胺化合物治疗或者预防自体免疫性疾病的方法 |
CA2533377C (en) | 2003-07-30 | 2012-11-27 | Rigel Pharmaceuticals, Inc. | Methods of treating or preventing autoimmune diseases with 2,4-pyrimidinediamine compounds |
WO2005013996A2 (en) * | 2003-08-07 | 2005-02-17 | Rigel Pharmaceuticals, Inc. | 2,4-pyrimidinediamine compounds and uses as anti-proliferative agents |
CA2566531A1 (en) * | 2004-05-18 | 2005-12-15 | Rigel Pharmaceuticals, Inc. | Cycloalkyl substituted pyrimidinediamine compounds and their uses |
EP1761518A1 (en) * | 2004-06-18 | 2007-03-14 | Neurosearch A/S | Novel alkyl substituted piperidine derivatives as monoamine neurotransmitter re-uptake inhibitors |
WO2006004776A1 (en) | 2004-06-29 | 2006-01-12 | Rigel Pharmaceuticals, Inc. | 4-pyrimidineamine compounds and their uses as anti-proliferative agents |
WO2006028833A1 (en) * | 2004-09-01 | 2006-03-16 | Rigel Pharmaceuticals, Inc. | Synthesis of 2,4-pyrimidinediamine compounds |
CA2580838A1 (en) * | 2004-09-27 | 2006-04-06 | Amgen Inc. | Substituted heterocyclic compounds and methods of use |
GB2420559B (en) * | 2004-11-15 | 2008-08-06 | Rigel Pharmaceuticals Inc | Stereoisomerically enriched 3-aminocarbonyl bicycloheptene pyrimidinediamine compounds and their uses |
CA2584295C (en) * | 2004-11-24 | 2014-08-26 | Rigel Pharmaceuticals, Inc. | Spiro-2, 4-pyrimidinediamine compounds and their uses |
ES2337496T3 (es) | 2005-01-19 | 2010-04-26 | Rigel Pharmaceuticals, Inc. | Profarmacos de compuestos de 2,4-pirimidindiamina y sus usos. |
ES2555063T3 (es) | 2005-02-04 | 2015-12-28 | Astrazeneca Ab | Derivados de pirazolilaminopiridina útiles como inhibidores de quinasas |
US8227455B2 (en) | 2005-04-18 | 2012-07-24 | Rigel Pharmaceuticals, Inc. | Methods of treating cell proliferative disorders |
US20060270694A1 (en) * | 2005-05-03 | 2006-11-30 | Rigel Pharmaceuticals, Inc. | JAK kinase inhibitors and their uses |
US20070203161A1 (en) * | 2006-02-24 | 2007-08-30 | Rigel Pharmaceuticals, Inc. | Compositions and methods for inhibition of the jak pathway |
JP5225079B2 (ja) * | 2005-06-08 | 2013-07-03 | ライジェル ファーマシューティカルズ, インコーポレイテッド | Jak経路の阻害のための組成物および方法 |
US7576053B2 (en) | 2005-06-13 | 2009-08-18 | Rigel Pharmaceuticals, Inc. | Methods and compositions for treating degenerative bone disorders |
DE602005000514T2 (de) * | 2005-06-17 | 2007-10-25 | Magneti Marelli Powertrain S.P.A. | Brennstoffeinspritzventil |
US20070117775A1 (en) * | 2005-10-31 | 2007-05-24 | Rigel Pharmaceuticals, Inc. | Compositions and Methods For Treating Inflammatory Disorders |
US8133900B2 (en) * | 2005-11-01 | 2012-03-13 | Targegen, Inc. | Use of bi-aryl meta-pyrimidine inhibitors of kinases |
PT1951684T (pt) * | 2005-11-01 | 2016-10-13 | Targegen Inc | Inibidores de cinases de tipo biaril-meta-pirimidina |
US8604042B2 (en) * | 2005-11-01 | 2013-12-10 | Targegen, Inc. | Bi-aryl meta-pyrimidine inhibitors of kinases |
US7713987B2 (en) * | 2005-12-06 | 2010-05-11 | Rigel Pharmaceuticals, Inc. | Pyrimidine-2,4-diamines and their uses |
JP2009520038A (ja) * | 2005-12-19 | 2009-05-21 | ジェネンテック・インコーポレーテッド | ピリミジンキナーゼインヒビター |
WO2007085540A1 (en) * | 2006-01-27 | 2007-08-02 | Glaxo Group Limited | 1h-indaz0l-4-yl-2 , 4-pyrimidinediamine derivatives |
SI1984357T1 (sl) | 2006-02-17 | 2014-02-28 | Rigel Pharmaceuticals, Inc. | Spojine 2,4-pirimidindiamina za zdravljenje ali preventivo avtoimunih bolezni |
JP2009528295A (ja) | 2006-02-24 | 2009-08-06 | ライジェル ファーマシューティカルズ, インコーポレイテッド | Jak経路の阻害のための組成物および方法 |
US20070293494A1 (en) | 2006-06-15 | 2007-12-20 | Djung Jane F | 2-Anilino-4-(Heterocyclic) Amino-Pyrimidines |
AU2007257701A1 (en) | 2006-06-15 | 2007-12-21 | Boehringer Ingelheim International Gmbh | 2-anilino-4-aminoalkyleneaminopyrimidines |
CA2673125C (en) * | 2006-10-19 | 2015-04-21 | Rigel Pharmaceuticals, Inc. | Compositions and methods for inhibition of the jak pathway |
ES2633318T3 (es) | 2006-10-23 | 2017-09-20 | Cephalon, Inc. | Derivados bicíclicos fusionados de 2,4-diaminopirimidina como inhibidores de ALK y c-Met |
US8163902B2 (en) | 2006-11-21 | 2012-04-24 | Rigel Pharmaceuticals, Inc. | Prodrugs of 2,4-pyrimidinediamine compounds and their uses |
EP1939185A1 (de) * | 2006-12-20 | 2008-07-02 | Bayer Schering Pharma Aktiengesellschaft | Neuartige Hetaryl-Phenylendiamin-Pyrimidine als Proteinkinaseinhibitoren zur Behandlung von Krebs |
DE102007010801A1 (de) | 2007-03-02 | 2008-09-04 | Bayer Cropscience Ag | Diaminopyrimidine als Fungizide |
US7947698B2 (en) | 2007-03-23 | 2011-05-24 | Rigel Pharmaceuticals, Inc. | Compositions and methods for inhibition of the JAK pathway |
US7834024B2 (en) | 2007-03-26 | 2010-11-16 | Rigel Pharmaceuticals, Inc. | Compositions and methods for inhibition of the JAK pathway |
WO2008131000A2 (en) * | 2007-04-16 | 2008-10-30 | Abbott Laboratories | 7-substituted indole mcl-1 inhibitors |
CA2693594A1 (en) * | 2007-07-17 | 2009-01-22 | Rigel Pharmaceuticals, Inc. | Cyclic amine substituted pyrimidinediamines as pkc inhibitors |
US20090088371A1 (en) * | 2007-08-28 | 2009-04-02 | Rigel Pharmaceuticals, Inc. | Combination therapy with syk kinase inhibitor |
BRPI0815979A2 (pt) | 2007-08-28 | 2017-06-13 | Irm Llc | compostos e composições com inibidores de quinase, bem como uso dos mesmos |
RU2458925C2 (ru) * | 2007-09-05 | 2012-08-20 | Райджел Фармасьютикалз, Инк. | Ксинафоатная соль n4-[(2,2-дифтор-4н-бензо[1,4]оксазин-3-он)-6-ил]-5-фтор-n2-[3-(метиламинокарбонилметиленокси)фенил]-2,4-пиримидиндиамина |
NZ587589A (en) | 2008-02-15 | 2012-10-26 | Rigel Pharmaceuticals Inc | Pyrimidine-2-amine compounds and their use as inhibitors of jak kinases |
BRPI0911228A2 (pt) * | 2008-04-07 | 2017-05-30 | Irm Llc | compostos e composições como inibidores de proteínas quinase |
PT2323993E (pt) | 2008-04-16 | 2015-10-12 | Portola Pharm Inc | 2,6-diamino-pirimidina-5-il-carboxamidas como inibidores de quinasses syk ou jak |
SG2014015085A (en) | 2008-04-16 | 2014-06-27 | Portola Pharm Inc | 2,6-diamino-pyrimidin-5-yl-carboxamides as syk or jak kinases inhibitors |
US8138339B2 (en) | 2008-04-16 | 2012-03-20 | Portola Pharmaceuticals, Inc. | Inhibitors of protein kinases |
NZ588830A (en) * | 2008-04-22 | 2012-11-30 | Portola Pharm Inc | Inhibitors of protein kinases |
EP2300013B2 (en) | 2008-05-21 | 2024-11-13 | Takeda Pharmaceutical Company Limited | Phosphorous derivatives as kinase inhibitors |
US9273077B2 (en) | 2008-05-21 | 2016-03-01 | Ariad Pharmaceuticals, Inc. | Phosphorus derivatives as kinase inhibitors |
US8445505B2 (en) | 2008-06-25 | 2013-05-21 | Irm Llc | Pyrimidine derivatives as kinase inhibitors |
UY31929A (es) | 2008-06-25 | 2010-01-05 | Irm Llc | Compuestos y composiciones como inhibidores de cinasa |
AU2009262198B2 (en) * | 2008-06-25 | 2012-09-27 | Irm Llc | Pyrimidine derivatives as kinase inhibitors |
RU2536584C2 (ru) | 2008-06-27 | 2014-12-27 | Авила Терапьютикс, Инк. | Гетероарильные соединения и их применение |
US8338439B2 (en) * | 2008-06-27 | 2012-12-25 | Celgene Avilomics Research, Inc. | 2,4-disubstituted pyrimidines useful as kinase inhibitors |
US11351168B1 (en) | 2008-06-27 | 2022-06-07 | Celgene Car Llc | 2,4-disubstituted pyrimidines useful as kinase inhibitors |
EP2161259A1 (de) | 2008-09-03 | 2010-03-10 | Bayer CropScience AG | 4-Halogenalkylsubstituierte Diaminopyrimidine als Fungizide |
WO2010027002A1 (ja) * | 2008-09-05 | 2010-03-11 | 塩野義製薬株式会社 | Pi3k阻害活性を有する縮環モルホリン誘導体 |
WO2010078369A2 (en) | 2008-12-30 | 2010-07-08 | Rigel Pharmaceuticals, Inc. | Pyrimidinediamine kinase inhibitors |
JP5781942B2 (ja) * | 2009-01-14 | 2015-09-24 | ライジェル ファーマシューティカルズ, インコーポレイテッド | 2,4−ピリミジンジアミン化合物を用いた炎症性障害の治療法 |
CN102292333B (zh) * | 2009-01-15 | 2015-05-13 | 里格尔药品股份有限公司 | 蛋白激酶c抑制剂及其用途 |
US8377924B2 (en) * | 2009-01-21 | 2013-02-19 | Rigel Pharmaceuticals Inc. | Protein kinase C inhibitors and uses thereof |
US8324200B2 (en) | 2009-01-23 | 2012-12-04 | Rigel Pharmaceuticals, Inc. | Compositions and methods for inhibition of the JAK pathway |
EP2440559B1 (en) | 2009-05-05 | 2018-01-10 | Dana-Farber Cancer Institute, Inc. | Egfr inhibitors and methods of treating disorders |
US8367689B2 (en) * | 2009-05-06 | 2013-02-05 | Portola Pharmaceuticals, Inc. | Inhibitors of JAK |
UA108077C2 (xx) | 2009-07-02 | 2015-03-25 | Синтез динатрієвої солі n4-(2,2-диметил-4-$(дигідрофосфонокси)метил]-3-оксо-5-піридо$1,4]оксазин-6-іл)-5-фтор-n2-(3,4,5-триметоксифеніл)-2,4-піримідиндіаміну | |
US20110015155A1 (en) | 2009-07-17 | 2011-01-20 | Rigel Pharmaceuticals, Inc. | Deuterated 2, 4-Pyrimidinediamine Compounds and Prodrugs Thereof and Their Uses |
CN106420756A (zh) * | 2009-07-28 | 2017-02-22 | 里格尔药品股份有限公司 | 抑制jak途径的组合物和方法 |
CN102002121A (zh) | 2009-08-31 | 2011-04-06 | 住友化学株式会社 | 树脂,抗蚀剂组合物和用于制造抗蚀剂图案的方法 |
WO2011063241A1 (en) | 2009-11-20 | 2011-05-26 | Rigel Pharmaceuticals, Inc. | 2,4-pyrimidinediamine compounds and prodrugs thereof and their uses |
CA2780759A1 (en) | 2009-12-01 | 2011-06-09 | Rigel Pharmaceuticals, Inc. | Protein kinase c inhibitors and uses thereof |
EP3489236B1 (en) | 2009-12-23 | 2020-09-30 | Takeda Pharmaceutical Company Limited | Process for the preparation of fused heteroaromatic pyrrolidinones |
WO2011103196A1 (en) * | 2010-02-17 | 2011-08-25 | Amgen Inc. | Aryl carboxamide derivatives as sodium channel inhibitors for treatment of pain |
US8618095B2 (en) | 2010-04-13 | 2013-12-31 | Rigel Pharmaceuticals, Inc. | 2, 4-pyrimidinediamine compounds and prodrugs thereof and their uses |
EP2571867B1 (en) | 2010-05-21 | 2015-11-04 | Noviga Research AB | Novel pyrimidine derivatives |
CN103038230B (zh) | 2010-06-04 | 2016-05-25 | 霍夫曼-拉罗奇有限公司 | 作为lrrk2调节剂的氨基嘧啶衍生物 |
EP2595982B1 (en) | 2010-07-21 | 2018-06-13 | Rigel Pharmaceuticals, Inc. | Protein kinase c inhibitors and uses thereof |
US9063414B2 (en) | 2010-07-28 | 2015-06-23 | Sumitomo Chemical Company, Limited | Photoresist composition |
MX347331B (es) | 2010-07-28 | 2017-04-21 | Rigel Pharmaceuticals Inc | Composiciones y metodos para inhibicion de la via jak. |
SG187796A1 (en) | 2010-08-10 | 2013-03-28 | Celgene Avilomics Res Inc | Besylate salt of a btk inhibitor |
JP6195692B2 (ja) | 2010-08-30 | 2017-09-13 | 住友化学株式会社 | レジスト組成物及びレジストパターンの製造方法並びに新規化合物及び樹脂 |
JP2012102088A (ja) * | 2010-10-14 | 2012-05-31 | Sumitomo Chemical Co Ltd | ヘテロ芳香環化合物およびその有害生物防除用途 |
US10028975B2 (en) | 2010-10-19 | 2018-07-24 | Beth Israel Deaconess Medical Center, Inc. | Methods for treating ischemia-reperfusion injury |
WO2012061428A2 (en) | 2010-11-01 | 2012-05-10 | Portola Pharmaceuticals, Inc. | Nicotinamides as jak kinase modulators |
WO2012061415A1 (en) | 2010-11-01 | 2012-05-10 | Portola Pharmaceuticals, Inc. | Oxypyrimidines as syk modulators |
EP3176154B1 (en) | 2010-11-01 | 2019-02-20 | Portola Pharmaceuticals, Inc. | Benzamides and nicotinamides as syk modulators |
SG10201508958WA (en) | 2010-11-01 | 2015-11-27 | Celgene Avilomics Res Inc | Heterocyclic Compounds And Uses Thereof |
JP5956999B2 (ja) | 2010-11-01 | 2016-07-27 | セルジーン アヴィロミクス リサーチ, インコーポレイテッド | ヘテロアリール化合物およびその使用 |
CA2816957A1 (en) | 2010-11-07 | 2012-05-10 | Targegen, Inc. | Compositions and methods for treating myelofibrosis |
CA2812669C (en) * | 2010-11-10 | 2018-11-06 | F. Hoffmann-La Roche Ag | Pyrazole aminopyrimidine derivatives as lrrk2 modulators |
US8796255B2 (en) | 2010-11-10 | 2014-08-05 | Celgene Avilomics Research, Inc | Mutant-selective EGFR inhibitors and uses thereof |
JP5879834B2 (ja) | 2010-11-15 | 2016-03-08 | 住友化学株式会社 | 塩、レジスト組成物及びレジストパターンの製造方法 |
EP2489663A1 (en) | 2011-02-16 | 2012-08-22 | Almirall, S.A. | Compounds as syk kinase inhibitors |
JP5947053B2 (ja) | 2011-02-25 | 2016-07-06 | 住友化学株式会社 | レジスト組成物及びレジストパターンの製造方法 |
JP5947051B2 (ja) | 2011-02-25 | 2016-07-06 | 住友化学株式会社 | レジスト組成物及びレジストパターンの製造方法 |
JP6034025B2 (ja) | 2011-02-25 | 2016-11-30 | 住友化学株式会社 | レジスト組成物及びレジストパターンの製造方法 |
JP5898520B2 (ja) | 2011-02-25 | 2016-04-06 | 住友化学株式会社 | レジスト組成物及びレジストパターンの製造方法 |
JP5829939B2 (ja) | 2011-02-25 | 2015-12-09 | 住友化学株式会社 | レジスト組成物及びレジストパターンの製造方法 |
JP5829940B2 (ja) | 2011-02-25 | 2015-12-09 | 住友化学株式会社 | レジスト組成物及びレジストパターンの製造方法 |
JP5829941B2 (ja) | 2011-02-25 | 2015-12-09 | 住友化学株式会社 | レジスト組成物及びレジストパターンの製造方法 |
JP5898521B2 (ja) | 2011-02-25 | 2016-04-06 | 住友化学株式会社 | レジスト組成物及びレジストパターンの製造方法 |
JP6034026B2 (ja) | 2011-02-25 | 2016-11-30 | 住友化学株式会社 | レジスト組成物及びレジストパターンの製造方法 |
CA2830129C (en) | 2011-03-24 | 2016-07-19 | Chemilia Ab | Novel pyrimidine derivatives |
WO2012151561A1 (en) | 2011-05-04 | 2012-11-08 | Ariad Pharmaceuticals, Inc. | Compounds for inhibiting cell proliferation in egfr-driven cancers |
AU2012253886A1 (en) | 2011-05-10 | 2013-10-31 | Merck Sharp & Dohme Corp. | Pyridyl aminopyridines as Syk inhibitors |
KR20140028062A (ko) | 2011-05-10 | 2014-03-07 | 머크 샤프 앤드 돔 코포레이션 | Syk 억제제로서의 아미노피리미딘 |
WO2012154518A1 (en) | 2011-05-10 | 2012-11-15 | Merck Sharp & Dohme Corp. | Bipyridylaminopyridines as syk inhibitors |
WO2012177714A1 (en) | 2011-06-22 | 2012-12-27 | Takeda Pharmaceutical Company Limited | Substituted 6-aza-isoindolin-1-one derivatives |
JP6013799B2 (ja) | 2011-07-19 | 2016-10-25 | 住友化学株式会社 | レジスト組成物及びレジストパターンの製造方法 |
JP6013797B2 (ja) | 2011-07-19 | 2016-10-25 | 住友化学株式会社 | レジスト組成物及びレジストパターンの製造方法 |
JP5990041B2 (ja) | 2011-07-19 | 2016-09-07 | 住友化学株式会社 | レジスト組成物及びレジストパターンの製造方法 |
JP5977595B2 (ja) | 2011-07-19 | 2016-08-24 | 住友化学株式会社 | レジスト組成物及びレジストパターンの製造方法 |
JP6013798B2 (ja) | 2011-07-19 | 2016-10-25 | 住友化学株式会社 | レジスト組成物及びレジストパターンの製造方法 |
JP5912912B2 (ja) | 2011-07-19 | 2016-04-27 | 住友化学株式会社 | レジスト組成物及びレジストパターンの製造方法 |
JP5985898B2 (ja) | 2011-07-19 | 2016-09-06 | 住友化学株式会社 | レジスト組成物及びレジストパターンの製造方法 |
JP5886696B2 (ja) | 2011-07-19 | 2016-03-16 | 住友化学株式会社 | レジスト組成物及びレジストパターンの製造方法 |
JP6189020B2 (ja) | 2011-07-19 | 2017-08-30 | 住友化学株式会社 | レジスト組成物及びレジストパターンの製造方法 |
JP6130630B2 (ja) | 2011-07-19 | 2017-05-17 | 住友化学株式会社 | レジスト組成物及びレジストパターンの製造方法 |
JP5977593B2 (ja) | 2011-07-19 | 2016-08-24 | 住友化学株式会社 | レジスト組成物及びレジストパターンの製造方法 |
JP5977594B2 (ja) | 2011-07-19 | 2016-08-24 | 住友化学株式会社 | レジスト組成物及びレジストパターンの製造方法 |
JP5996944B2 (ja) | 2011-07-19 | 2016-09-21 | 住友化学株式会社 | レジスト組成物及びレジストパターンの製造方法 |
JP6130631B2 (ja) | 2011-07-19 | 2017-05-17 | 住友化学株式会社 | レジスト組成物及びレジストパターンの製造方法 |
DK2736487T4 (da) | 2011-07-28 | 2024-11-04 | Rigel Pharmaceuticals Inc | Nye (trimethoxyphenylamino)pyrimidinyl-formuleringer |
CN103974955B (zh) | 2011-08-23 | 2018-06-19 | 阿萨纳生物科技有限责任公司 | 嘧啶并-哒嗪酮化合物及其用途 |
US9221798B2 (en) * | 2011-09-05 | 2015-12-29 | Zhejian Hisun Pharmaceutical Co., Ltd. | 4-substituted-(3-substituted-1H-pyrazole-5-amino)-pyrimidine derivatives having activity of inhibiting protein kinase and use thereof |
EP2763975B1 (en) | 2011-10-05 | 2016-04-06 | Merck Sharp & Dohme Corp. | 3-pyridyl carboxamide-containing spleen tyrosine kinase (syk) inhibitors |
EP2763976B1 (en) | 2011-10-05 | 2016-05-18 | Merck Sharp & Dohme Corp. | 2-pyridyl carboxamide-containing spleen tyrosine kinase (syk) inhibitors |
EP2763974B1 (en) | 2011-10-05 | 2016-09-14 | Merck Sharp & Dohme Corp. | Phenyl carboxamide-containing spleen tyrosine kinase (syk) inhibitors |
WO2013063401A1 (en) | 2011-10-28 | 2013-05-02 | Celgene Avilomics Research, Inc. | Methods of treating a bruton's tyrosine kinase disease or disorder |
JP6039683B2 (ja) | 2011-11-23 | 2016-12-07 | ポートラ ファーマシューティカルズ, インコーポレイテッド | ピラジンキナーゼ阻害剤 |
AU2012370450B2 (en) * | 2012-02-21 | 2017-02-02 | Merck Patent Gmbh | Cyclic diaminopyrimidine derivatives |
US9056839B2 (en) | 2012-03-15 | 2015-06-16 | Celgene Avilomics Research, Inc. | Solid forms of an epidermal growth factor receptor kinase inhibitor |
JP6317320B2 (ja) | 2012-03-15 | 2018-04-25 | セルジーン シーエーアール エルエルシー | 上皮成長因子受容体キナーゼ阻害剤の塩 |
AU2013204563B2 (en) | 2012-05-05 | 2016-05-19 | Takeda Pharmaceutical Company Limited | Compounds for inhibiting cell proliferation in EGFR-driven cancers |
US20130310340A1 (en) | 2012-05-16 | 2013-11-21 | Rigel Pharmaceuticals, Inc. | Method of treating muscular degradation |
US9242984B2 (en) | 2012-06-20 | 2016-01-26 | Merck Sharp & Dohme Corp. | Pyrazolyl derivatives as Syk inhibitors |
EP2863913B1 (en) | 2012-06-20 | 2018-09-12 | Merck Sharp & Dohme Corp. | Imidazolyl analogs as syk inhibitors |
US9376418B2 (en) | 2012-06-22 | 2016-06-28 | Merck Sharp & Dohme Corp. | Substituted pyridine spleen tyrosine kinase (SYK) inhibitors |
EP2863915B1 (en) | 2012-06-22 | 2017-12-06 | Merck Sharp & Dohme Corp. | SUBSTITUTED DIAZINE AND TRIAZINE SPLEEN TYROSINE KINASE (Syk) INHIBITORS |
KR101446742B1 (ko) | 2012-08-10 | 2014-10-01 | 한국화학연구원 | N2,n4-비스(4-(피페라진-1-일)페닐)피리미딘-2,4-디아민 유도체 또는 이의 약학적으로 허용가능한 염 및 이를 유효성분으로 함유하는 암의 예방 또는 치료용 약학적 조성물 |
US9353066B2 (en) | 2012-08-20 | 2016-05-31 | Merck Sharp & Dohme Corp. | Substituted phenyl-Spleen Tyrosine Kinase (Syk) inhibitors |
WO2014048065A1 (en) | 2012-09-28 | 2014-04-03 | Merck Sharp & Dohme Corp. | Triazolyl derivatives as syk inhibitors |
EP2903970A4 (en) | 2012-10-08 | 2016-11-30 | Portola Pharm Inc | SUBSTITUTED PYRIMIDINYL KINASE INHIBITORS |
JP6357167B2 (ja) | 2012-12-04 | 2018-07-11 | ライジェル ファーマシューティカルズ, インコーポレイテッド | プロテインキナーゼc阻害剤およびそれらの用途 |
US9624210B2 (en) | 2012-12-12 | 2017-04-18 | Merck Sharp & Dohme Corp. | Amino-pyrimidine-containing spleen tyrosine kinase (Syk) inhibitors |
US9598405B2 (en) | 2012-12-21 | 2017-03-21 | Merck Sharp & Dohme Corp. | Thiazole-substituted aminopyridines as spleen tyrosine kinase inhibitors |
EP2935226A4 (en) | 2012-12-21 | 2016-11-02 | Celgene Avilomics Res Inc | HETEROARYL COMPOUNDS AND USES THEREOF |
EP2948150A1 (en) | 2013-01-25 | 2015-12-02 | Rigel Pharmaceuticals, Inc. | Compounds and methods for treating inflammatory bowel diseases |
EP2953457B1 (en) | 2013-02-08 | 2020-04-08 | Celgene CAR LLC | Erk inhibitors and uses thereof |
CA2904610A1 (en) | 2013-03-14 | 2014-09-25 | Rigel Pharmaceuticals, Inc. | Protein kinase c inhibitors and uses thereof |
US9611283B1 (en) | 2013-04-10 | 2017-04-04 | Ariad Pharmaceuticals, Inc. | Methods for inhibiting cell proliferation in ALK-driven cancers |
EP2988749B1 (en) | 2013-04-26 | 2019-08-14 | Merck Sharp & Dohme Corp. | Thiazole-substituted aminopyrimidines as spleen tyrosine kinase inhibitors |
US9745295B2 (en) | 2013-04-26 | 2017-08-29 | Merck Sharp & Dohme Corp. | Thiazole-substituted aminoheteroaryls as spleen tyrosine kinase inhibitors |
US9492471B2 (en) | 2013-08-27 | 2016-11-15 | Celgene Avilomics Research, Inc. | Methods of treating a disease or disorder associated with Bruton'S Tyrosine Kinase |
EP3082807B1 (en) | 2013-12-20 | 2018-07-04 | Merck Sharp & Dohme Corp. | Thiazole-substituted aminoheteroaryls as spleen tyrosine kinase inhibitors |
US9415049B2 (en) | 2013-12-20 | 2016-08-16 | Celgene Avilomics Research, Inc. | Heteroaryl compounds and uses thereof |
WO2015095445A1 (en) | 2013-12-20 | 2015-06-25 | Merck Sharp & Dohme Corp. | Thiazole-substituted aminoheteroaryls as spleen tyrosine kinase inhibitors |
JP6522005B2 (ja) | 2013-12-20 | 2019-05-29 | ライジェル ファーマシューティカルズ, インコーポレイテッド | 薬学的方法および中間体 |
EP3083560B1 (en) | 2013-12-20 | 2021-10-27 | Merck Sharp & Dohme Corp. | Thiazole-substituted aminoheteroaryls as spleen tyrosine kinase inhibitors |
EP3116506B1 (en) | 2014-03-13 | 2019-04-17 | Merck Sharp & Dohme Corp. | 2-pyrazine carboxamides as spleen tyrosine kinase inhibitors |
CN104926824B (zh) * | 2014-03-17 | 2017-07-07 | 广东东阳光药业有限公司 | 取代的杂芳基化合物及其组合物和用途 |
US9394281B2 (en) | 2014-03-28 | 2016-07-19 | Calitor Sciences, Llc | Substituted heteroaryl compounds and methods of use |
CN105017159B (zh) * | 2014-04-28 | 2019-05-17 | 四川大学 | 5-氟-2,4-二取代氨基嘧啶衍生物及其制备方法和用途 |
WO2016025561A1 (en) | 2014-08-13 | 2016-02-18 | Celgene Avilomics Research, Inc. | Forms and compositions of an erk inhibitor |
US20180296579A1 (en) | 2015-04-24 | 2018-10-18 | Rigel Pharmaceuticals, Inc. | Methods of treating ibrutinib-resistant disease |
AU2016290950A1 (en) * | 2015-07-09 | 2018-01-18 | Merck Patent Gmbh | Pyrimidine derivatives as BTK inhibitors and uses thereof |
EP3347097B1 (en) | 2015-09-11 | 2021-02-24 | Sunshine Lake Pharma Co., Ltd. | Substituted aminopyrimidine derivatives as modulators of the kinases jak, flt3 and aurora |
US10258402B2 (en) | 2016-01-04 | 2019-04-16 | OsteoCertus, LLC | Orthopedic bone plate system |
US10478237B2 (en) | 2016-01-04 | 2019-11-19 | OsteoCertus, LLC | Orthopedic bone plate system |
US10939943B2 (en) | 2016-01-04 | 2021-03-09 | OsteoCertus, LLC | Orthopedic bone plate system |
US11203576B2 (en) | 2016-03-11 | 2021-12-21 | H. Lee Moffitt Cancer Center And Research Institute, Inc. | Aurora kinase and Janus kinase inhibitors for prevention of graft versus host disease |
RU2621187C1 (ru) * | 2016-05-13 | 2017-06-01 | Общество с ограниченной ответственностью "Молекулярные Технологии" | Новая кристаллическая солевая форма 2,2-диметил-6-((4-((3,4,5-триметоксифенил)амино)-1,3,5-триазин-2-ил)амино)-2н-пиридо[3,2-в][1,4]оксазин-3(4н)-она для медицинского применения |
KR20190140011A (ko) | 2017-04-28 | 2019-12-18 | 아사나 바이오사이언시스 엘엘씨 | 아토피성 피부염을 치료하고, 활성 약학적 성분의 안정성을 개선하기 위한 제형물, 방법, 키트, 및 투여형 |
SG11202002475TA (en) | 2017-10-19 | 2020-04-29 | Bayer Animal Health Gmbh | Use of fused heteroaromatic pyrrolidones for treatment and prevention of diseases in animals |
PT3966207T (pt) | 2019-05-10 | 2023-12-20 | Deciphera Pharmaceuticals Llc | Inibidores de autofagia de fenilaminopirimidina amida e métodos de utilização dos mesmos |
EP4295846A3 (en) | 2019-05-10 | 2024-02-28 | Deciphera Pharmaceuticals, LLC | Heteroarylaminopyrimidine amide autophagy inhibitors and methods of use thereof |
WO2020243612A1 (en) | 2019-05-29 | 2020-12-03 | Rigel Pharmaceuticals, Inc. | Method of preventing and treating thrombosis |
BR112021025544A2 (pt) | 2019-06-17 | 2022-05-17 | Deciphera Pharmaceuticals Llc | Inibidores de autofagia de aminopirimidina amida e métodos de uso dos mesmos |
EP4009974A1 (en) | 2019-08-08 | 2022-06-15 | Rigel Pharmaceuticals, Inc. | Compounds and method for treating cytokine release syndrome |
EP4013420B1 (en) | 2019-08-14 | 2023-11-01 | Rigel Pharmaceuticals, Inc. | Method of blocking or ameliorating cytokine release syndrome |
Family Cites Families (265)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3159547A (en) | 1963-06-28 | 1964-12-01 | Abbott Lab | Method of lowering blood pressure with 4-(2-amino-4-pyrimidylamino)-benzene-sulfonamide |
US3320256A (en) | 1965-04-09 | 1967-05-16 | Hoffmann La Roche | Fluorinated imidazoo[1, 2-c]pyrimidines and pyrimido[1, 2-c]pyrimidines |
US4166452A (en) * | 1976-05-03 | 1979-09-04 | Generales Constantine D J Jr | Apparatus for testing human responses to stimuli |
US4256108A (en) * | 1977-04-07 | 1981-03-17 | Alza Corporation | Microporous-semipermeable laminated osmotic system |
US4265874A (en) * | 1980-04-25 | 1981-05-05 | Alza Corporation | Method of delivering drug with aid of effervescent activity generated in environment of use |
GR80171B (en) | 1983-08-29 | 1985-01-02 | Ciba Geigy Ag | N-(2-nitrophenyl)-4-aminopyrimidine derivatives process for the preparation thereof and use |
HU192875B (en) | 1984-10-05 | 1987-07-28 | Richter Gedeon Vegyeszet | Process for preparing 2-pyridinethiol derivatives |
JPH07100685B2 (ja) * | 1985-08-02 | 1995-11-01 | レオ・ファ−マシュ−ティカル・プロダクツ・リミテッド・エイ/エス(レ−ベンス・ケミスケ・ファブリック・プロデュクチオンスアクチ−セルスカブ) | 新規ビタミンd類似体 |
DE3618353A1 (de) | 1986-05-31 | 1987-12-03 | Hoechst Ag | Schaedlingsbekaempfungsmittel auf der basis von aminopyrimidin-derivaten sowie neue aminopyrimidin-verbindungen |
US4968781A (en) | 1987-04-02 | 1990-11-06 | Ciba-Geigy Corporation | Fiber-reactive dyes comprising a halopyrimidine for which a vinylsulfonyl or the like moiety is attached via a bridge member |
SU1499883A1 (ru) | 1987-11-24 | 1991-10-23 | Научно-исследовательский институт фармакологии АМН СССР | Дихлоргидрат 2,4-бис-(п-трет-бутиланилино)-5-окси-6-метилпиримидина, обладающий анальгетической и противовоспалительной активностью |
KR0144358B1 (ko) * | 1988-04-21 | 1998-07-15 | 피. 라이달 크리스텐슨 | 비타민 d 동족체 |
HU206337B (en) | 1988-12-29 | 1992-10-28 | Mitsui Petrochemical Ind | Process for producing pyrimidine derivatives and pharmaceutical compositions |
US4969781A (en) * | 1989-04-07 | 1990-11-13 | The B. F. Goodrich Company | Blind fastener hand tool |
IE63502B1 (en) | 1989-04-21 | 1995-05-03 | Zeneca Ltd | Aminopyrimidine derivatives useful for treating cardiovascular disorders |
US5179204A (en) | 1989-09-05 | 1993-01-12 | Hoechst-Roussel Pharmaceuticals Incorporated | N-substituted-4-pyrimidinamines and pyrimidinediamines |
US4983608A (en) | 1989-09-05 | 1991-01-08 | Hoechst-Roussell Pharmaceuticals, Inc. | N-substituted-4-pyrimidinamines and pyrimidinediamines |
JPH03127790A (ja) | 1989-10-11 | 1991-05-30 | Morishita Pharmaceut Co Ltd | N―(1h―テトラゾール―5―イル)―2―アニリノ―5―ピリミジンカルボキシアミド類及びその合成中間体 |
TW224941B (xx) | 1989-11-08 | 1994-06-11 | Yamanouchi Pharma Co Ltd | |
US5532228A (en) * | 1990-02-06 | 1996-07-02 | Schering Aktiengesellschaft | Side-chain homologous vitamin D derivatives, process for their production, pharmaceutical preparations containing these derivatives and their use as pharmaceutical agents |
DE4011682A1 (de) * | 1990-04-06 | 1991-10-10 | Schering Ag | 24-oxa-derivate in der vitamin d-reihe |
GB9012592D0 (en) | 1990-06-06 | 1990-07-25 | Smithkline Beecham Intercredit | Compounds |
DE4029650A1 (de) | 1990-09-19 | 1992-03-26 | Hoechst Ag | 2-anilino-pyrimidine, verfahren zu ihrer herstellung, sie enthaltene mittel und ihre verwendung als fungizide |
US5246948A (en) * | 1991-05-10 | 1993-09-21 | Takeda Chemical Industries, Ltd. | Pyridine derivatives, their production and use |
US5200400A (en) * | 1991-07-12 | 1993-04-06 | New England Deaconess Hospital Corporation | Method for inhibiting allograft rejection using photoactivatable nucleotides or nucleosides |
CA2074864A1 (en) | 1991-07-30 | 1993-01-31 | Carmen Almansa | Tetralones with pharmacological activity |
US5728536A (en) * | 1993-07-29 | 1998-03-17 | St. Jude Children's Research Hospital | Jak kinases and regulation of Cytokine signal transduction |
DE4141746A1 (de) * | 1991-12-13 | 1993-06-17 | Schering Ag | 20-methyl-substituierte vitamin d-derivate |
US5521184A (en) | 1992-04-03 | 1996-05-28 | Ciba-Geigy Corporation | Pyrimidine derivatives and processes for the preparation thereof |
US5194431A (en) * | 1992-07-08 | 1993-03-16 | Wisconsin Alumni Research Foundation | 24-cyclopropane vitamin D derivatives |
TW287160B (xx) | 1992-12-10 | 1996-10-01 | Hoffmann La Roche | |
AU692484B2 (en) | 1993-10-12 | 1998-06-11 | Du Pont Pharmaceuticals Company | 1N-alkyl-N-arylpyrimidinamines and derivatives thereof |
IL112290A (en) | 1994-01-12 | 1999-01-26 | Novartis Ag | Transformed aryl and the troiryl pyrimidines and herbicides containing them |
CA2150609C (en) | 1994-06-01 | 1998-12-08 | Mikiro Yanaka | Pyrimidine derivatives and pharmaceutical composition |
US5733932A (en) | 1995-01-06 | 1998-03-31 | The Picower Institute For Medical Research | Compounds and methods of use to derivatize neighboring lysine residues in proteins under physiological conditions |
US6242434B1 (en) * | 1997-08-08 | 2001-06-05 | Bone Care International, Inc. | 24-hydroxyvitamin D, analogs and uses thereof |
US6316635B1 (en) * | 1995-06-07 | 2001-11-13 | Sugen, Inc. | 2-indolinone derivatives as modulators of protein kinase activity |
US5700904A (en) | 1995-06-07 | 1997-12-23 | Eli Lilly And Company | Preparation of an acylated protein powder |
GB9516121D0 (en) | 1995-08-05 | 1995-10-04 | Pfizer Ltd | Organometallic addition to ketones |
JP2002515023A (ja) | 1995-08-24 | 2002-05-21 | ビーエーエスエフ アクチェンゲゼルシャフト | N−複素環化合物、その製造用中間体、それを含む組成物及び有害菌類防除にそれを使用する方法 |
GB9523675D0 (en) | 1995-11-20 | 1996-01-24 | Celltech Therapeutics Ltd | Chemical compounds |
JP4058129B2 (ja) * | 1996-03-18 | 2008-03-05 | 株式会社資生堂 | ピリジン誘導体及び抗潰瘍剤、抗菌剤 |
TW440563B (en) | 1996-05-23 | 2001-06-16 | Hoffmann La Roche | Aryl pyrimidine derivatives and a pharmaceutical composition thereof |
US6696448B2 (en) * | 1996-06-05 | 2004-02-24 | Sugen, Inc. | 3-(piperazinylbenzylidenyl)-2-indolinone compounds and derivatives as protein tyrosine kinase inhibitors |
GB9619284D0 (en) | 1996-09-16 | 1996-10-30 | Celltech Therapeutics Ltd | Chemical compounds |
US6004985A (en) | 1996-10-09 | 1999-12-21 | Berlex Laboratories, Inc. | Thio acid derived monocylic N-heterocyclics as anticoagulants |
GB9705361D0 (en) | 1997-03-14 | 1997-04-30 | Celltech Therapeutics Ltd | Chemical compounds |
US6316429B1 (en) * | 1997-05-07 | 2001-11-13 | Sugen, Inc. | Bicyclic protein kinase inhibitors |
US6486185B1 (en) * | 1997-05-07 | 2002-11-26 | Sugen, Inc. | 3-heteroarylidene-2-indolinone protein kinase inhibitors |
US6987113B2 (en) * | 1997-06-11 | 2006-01-17 | Sugen, Inc. | Tyrosine kinase inhibitors |
SE9702401D0 (sv) * | 1997-06-19 | 1997-06-19 | Astra Ab | Pharmaceutical use |
GB9718913D0 (en) * | 1997-09-05 | 1997-11-12 | Glaxo Group Ltd | Substituted oxindole derivatives |
US6133305A (en) * | 1997-09-26 | 2000-10-17 | Sugen, Inc. | 3-(substituted)-2-indolinones compounds and use thereof as inhibitors of protein kinase activity |
US6093820A (en) * | 1997-10-02 | 2000-07-25 | Taro Pharmaceutical Industries Ltd. | Method and reagents for N-alkylating ureides |
US6022884A (en) | 1997-11-07 | 2000-02-08 | Amgen Inc. | Substituted pyridine compounds and methods of use |
GB9723859D0 (en) | 1997-11-12 | 1998-01-07 | Zeneca Ltd | Compound,composition and use |
DE19750701A1 (de) | 1997-11-15 | 1999-05-20 | Dystar Textilfarben Gmbh & Co | Verfahren zur Umsetzung von fluorsubstituierten Heterocyclen mit Aminen in Gegenwart von Phasentransfer-Katalysatoren |
WO1999031073A1 (fr) | 1997-12-15 | 1999-06-24 | Yamanouchi Pharmaceutical Co., Ltd. | Nouveaux derives de pyrimidine-5-carboxamide |
WO1999033846A2 (en) | 1997-12-31 | 1999-07-08 | The University Of Kansas | Water soluble prodrugs of secondary and tertiary amine containing drugs and methods of making thereof |
EP1054874B1 (en) * | 1998-02-13 | 2002-08-28 | PHARMACIA & UPJOHN COMPANY | Substituted aminophenyl isoxazoline derivatives useful as antimicrobials |
IL137922A0 (en) | 1998-02-17 | 2001-10-31 | Tularik Inc | Anti-viral pyrimidine derivatives |
ES2193660T3 (es) | 1998-03-27 | 2003-11-01 | Janssen Pharmaceutica Nv | Derivados de pirimidina inhibidores de vih. |
BRPI9909191B8 (pt) | 1998-03-27 | 2021-07-06 | Janssen Pharmaceutica Nv | derivados de pirimidina inibidores do hiv, seu uso e composição farmacêutica que os compreende |
GB9806739D0 (en) | 1998-03-28 | 1998-05-27 | Univ Newcastle Ventures Ltd | Cyclin dependent kinase inhibitors |
WO1999050249A2 (en) | 1998-04-01 | 1999-10-07 | Du Pont Pharmaceuticals Company | Pyrimidines and triazines as integrin antagonists |
WO1999052942A2 (en) * | 1998-04-15 | 1999-10-21 | Genset | Genomic sequence of the 5-lipoxygenase-activating protein (flap), polymorphic markers thereof and methods for detection of asthma |
HUP0102058A3 (en) | 1998-05-22 | 2002-05-28 | Smithkline Beecham Corp | Novel 2-alkyl substituted imidazole compounds, process for their preparation, pharmaceutical compositions containing them and their use |
JP2004504259A (ja) | 1998-06-30 | 2004-02-12 | パーカー ヒューズ インスティテュート | Jak−3インヒビターを用いたc−jun発現の阻害方法 |
CA2342503A1 (en) | 1998-08-21 | 2000-03-02 | Parker Hughes Institute | Quinazoline derivatives |
DE69933680T2 (de) | 1998-08-29 | 2007-08-23 | Astrazeneca Ab | Pyrimidine verbindungen |
DE19851421A1 (de) | 1998-11-07 | 2000-05-11 | Boehringer Ingelheim Pharma | Neue Pyrimidine, deren Herstellung und Verwendung |
EA004049B1 (ru) | 1998-11-10 | 2003-12-25 | Янссен Фармацевтика Н.В. | Пиримидины, ингибирующие репликацию вич |
EP1129068A1 (en) * | 1998-11-12 | 2001-09-05 | Ariad Pharmaceuticals, Inc. | Bicyclic signal transduction inhibitors, composition containing them and uses thereof |
US6127376A (en) | 1998-12-04 | 2000-10-03 | Berlex Laboratories, Inc. | Aryl and heterocyclyl substituted pyrimidine derivatives as anti-coagulants |
GB9828511D0 (en) | 1998-12-24 | 1999-02-17 | Zeneca Ltd | Chemical compounds |
US6841567B1 (en) | 1999-02-12 | 2005-01-11 | Cephalon, Inc. | Cyclic substituted fused pyrrolocarbazoles and isoindolones |
US6673908B1 (en) * | 1999-02-22 | 2004-01-06 | Nuvelo, Inc. | Tumor necrosis factor receptor 2 |
US6624171B1 (en) * | 1999-03-04 | 2003-09-23 | Smithkline Beecham Corporation | Substituted aza-oxindole derivatives |
GB9904995D0 (en) | 1999-03-04 | 1999-04-28 | Glaxo Group Ltd | Substituted aza-oxindole derivatives |
US6080747A (en) * | 1999-03-05 | 2000-06-27 | Hughes Institute | JAK-3 inhibitors for treating allergic disorders |
SE9901079D0 (sv) | 1999-03-23 | 1999-03-23 | Astra Ab | Novel compounds |
US6518286B1 (en) | 1999-03-26 | 2003-02-11 | Astrazeneca Ab | Compounds |
GB9907658D0 (en) | 1999-04-06 | 1999-05-26 | Zeneca Ltd | Chemical compounds |
EP1165522A1 (en) | 1999-04-06 | 2002-01-02 | Krenitsky Pharmaceuticals, Inc. | Neurotrophic thio substituted pyrimidines |
DE19917785A1 (de) | 1999-04-20 | 2000-10-26 | Bayer Ag | 2,4-Diamino-pyrimidin-Derivate |
AU5108000A (en) | 1999-06-10 | 2001-01-02 | Yamanouchi Pharmaceutical Co., Ltd. | Novel nitrogen-contaiing heterocyclic derivatives or salts thereof |
GB9914258D0 (en) | 1999-06-18 | 1999-08-18 | Celltech Therapeutics Ltd | Chemical compounds |
AU5636900A (en) | 1999-06-30 | 2001-01-31 | Merck & Co., Inc. | Src kinase inhibitor compounds |
TWI262914B (en) * | 1999-07-02 | 2006-10-01 | Agouron Pharma | Compounds and pharmaceutical compositions for inhibiting protein kinases |
GB9918035D0 (en) | 1999-07-30 | 1999-09-29 | Novartis Ag | Organic compounds |
DZ3186A1 (fr) | 1999-09-15 | 2001-03-22 | Warner Lambert Co | Ptéridinones utilisées comme inhibiteurs de kinase. |
DK1225874T3 (da) | 1999-09-24 | 2006-06-12 | Janssen Pharmaceutica Nv | Antivirale, faste dispersioner |
DE19945982A1 (de) | 1999-09-24 | 2001-03-29 | Knoll Ag | Geschwindigkeitsbestimmte Partikel |
CA2379640C (en) | 1999-09-30 | 2006-11-28 | Neurogen Corporation | Certain alkylene diamine-substituted heterocycles |
KR100317935B1 (ko) | 1999-10-20 | 2001-12-22 | 유승필 | 대사성 골질환 치료용 약제조성물 및 이의 제조방법 |
GB9924862D0 (en) | 1999-10-20 | 1999-12-22 | Celltech Therapeutics Ltd | Chemical compounds |
AU1026901A (en) | 1999-10-29 | 2001-05-08 | Syngenta Participations Ag | Novel herbicides |
AU4903201A (en) | 1999-11-30 | 2001-07-03 | Parker Hughes Institute | Inhibitors of thrombin induced platelet aggregation |
HU229671B1 (en) | 1999-12-10 | 2014-04-28 | Pfizer Prod Inc | Pyrrolo[2,3-d]pirimidine compounds |
CA2395520A1 (en) * | 1999-12-21 | 2001-06-28 | Sugen, Inc. | 4-substituted 7-aza-indolin-2-ones and their use as protein kinase inhibitors |
US20020065270A1 (en) | 1999-12-28 | 2002-05-30 | Moriarty Kevin Joseph | N-heterocyclic inhibitors of TNF-alpha expression |
WO2001047921A1 (en) | 1999-12-28 | 2001-07-05 | Pharmacopeia, Inc. | Pyrimidine and triazine kinase inhibitors |
AU2968701A (en) | 2000-01-24 | 2001-07-31 | Genzyme Corporation | Jak/stat pathway inhibitors and the uses thereof |
WO2001056993A2 (en) * | 2000-02-05 | 2001-08-09 | Vertex Pharmaceuticals Incorporated | Pyrazole compositions useful as inhibitors of erk |
KR20010111298A (ko) | 2000-02-05 | 2001-12-17 | 버텍스 파마슈티칼스 인코포레이티드 | Erk의 억제제로서 유용한 피라졸 조성물 |
WO2001060816A1 (en) | 2000-02-17 | 2001-08-23 | Amgen Inc. | Kinase inhibitors |
GB0004886D0 (en) * | 2000-03-01 | 2000-04-19 | Astrazeneca Uk Ltd | Chemical compounds |
GB0004890D0 (en) | 2000-03-01 | 2000-04-19 | Astrazeneca Uk Ltd | Chemical compounds |
GB0004888D0 (en) | 2000-03-01 | 2000-04-19 | Astrazeneca Uk Ltd | Chemical compounds |
GB0004887D0 (en) | 2000-03-01 | 2000-04-19 | Astrazeneca Uk Ltd | Chemical compounds |
US6525051B2 (en) | 2000-03-27 | 2003-02-25 | Schering Aktiengesellschaft | N-heterocyclic derivatives as NOS inhibitors |
AR028261A1 (es) | 2000-03-28 | 2003-04-30 | Wyeth Corp | Inhibidores triciclicos de la proteina quinasa |
US6608048B2 (en) * | 2000-03-28 | 2003-08-19 | Wyeth Holdings | Tricyclic protein kinase inhibitors |
WO2001085699A2 (en) | 2000-05-08 | 2001-11-15 | Janssen Pharmaceutica N.V. | Prodrugs of hiv replication inhibiting pyrimidines |
CA2406562C (en) | 2000-05-08 | 2009-09-15 | Janssen Pharmaceutica N.V. | Hiv replication inhibiting pyrimidines and triazines |
PL359563A1 (en) | 2000-06-26 | 2004-08-23 | Pfizer Products Inc. | Pyrrolo[2,3-d]pyrimidine compounds as immunosuppressive agents |
GB0016877D0 (en) * | 2000-07-11 | 2000-08-30 | Astrazeneca Ab | Chemical compounds |
US20050009876A1 (en) * | 2000-07-31 | 2005-01-13 | Bhagwat Shripad S. | Indazole compounds, compositions thereof and methods of treatment therewith |
AU2001283381A1 (en) | 2000-08-18 | 2002-03-04 | 3M Innovative Properties Company | Fluoroalkyl (meth)acrylate copolymer coating compositions |
ES2266258T3 (es) | 2000-09-15 | 2007-03-01 | Vertex Pharmaceuticals Incorporated | Compuestos de pirazol utiles como inhibidores de proteina cinasas. |
AU9654201A (en) * | 2000-10-02 | 2002-04-15 | Univ Emory | Triptolide analogs for the treatment of autoimmune and inflammatory disorders |
US6448401B1 (en) * | 2000-11-20 | 2002-09-10 | Bristol-Myers Squibb Company | Process for water soluble azole compounds |
WO2002043735A1 (en) | 2000-11-29 | 2002-06-06 | Parker Hughes Institute | Inhibitors of thrombin induced platelet aggregation |
US20020137755A1 (en) | 2000-12-04 | 2002-09-26 | Bilodeau Mark T. | Tyrosine kinase inhibitors |
US20020115173A1 (en) * | 2000-12-11 | 2002-08-22 | Children's Medical Center Corporation | Short peptides from the 'A-region' of protein kinases which selectively modulate protein kinase activity |
AU2002228922A1 (en) | 2000-12-12 | 2002-06-24 | Cytovia, Inc. | Substituted 2-aryl-4-arylaminopyrimidines and analogs as activators of caspases and inducers of apoptosis and the use thereof |
CA2432114A1 (en) * | 2000-12-20 | 2002-07-18 | Sugen, Inc. | 4-(hetero)aryl substituted indolinones |
AU2002234047A1 (en) | 2000-12-21 | 2002-07-01 | Vertex Pharmaceuticals Incorporated | Pyrazole compounds useful as protein kinase inhibitors |
JP4253188B2 (ja) | 2000-12-21 | 2009-04-08 | グラクソ グループ リミテッド | 血管新生制御剤としてのピリミジンアミン |
EP1363702A4 (en) * | 2001-01-30 | 2007-08-22 | Cytopia Pty Ltd | PROCESS FOR INHIBITING KINASES |
AUPR279101A0 (en) * | 2001-01-30 | 2001-02-22 | Cytopia Pty Ltd | Protein kinase signalling |
WO2002064096A2 (en) | 2001-02-16 | 2002-08-22 | Tularik Inc. | Methods of using pyrimidine-based antiviral agents |
GB0103926D0 (en) | 2001-02-17 | 2001-04-04 | Astrazeneca Ab | Chemical compounds |
BR0207096A (pt) | 2001-02-20 | 2004-01-20 | Astrazeneca Ab | Uso de um composto, compostos, formulação farmacêutica, e, método de tratamento e/ou profilaxia de condições associadas com a inibição de glicogênio sintase quinase-3 |
PL364625A1 (en) | 2001-02-23 | 2004-12-13 | Merck & Co, Inc. | N-substituted nonaryl-heterocyclic nmda/nr2b antagonists |
GB2373186A (en) | 2001-02-23 | 2002-09-18 | Astrazeneca Ab | Pharmaceutical combinations of a CCR3 antagonist and a compound which is usefulreatment of asthma, allergic disease or inflammation |
EP1975620A3 (en) | 2001-03-02 | 2008-12-24 | GPC Biotech AG | Three hybrid assay system |
RU2330024C2 (ru) * | 2001-05-29 | 2008-07-27 | Шеринг Акциенгезельшафт | Ингибирующие cdk-киназы пиримидины, способ их получения и их применение в качестве лекарственных средств |
MXPA03010961A (es) * | 2001-05-31 | 2004-02-27 | Vertex Pharma | Compuestos de tiazol utiles como inhibidores de proteinas cinasas. |
US7301023B2 (en) | 2001-05-31 | 2007-11-27 | Pfizer Inc. | Chiral salt resolution |
WO2002096905A1 (en) | 2001-06-01 | 2002-12-05 | Vertex Pharmaceuticals Incorporated | Thiazole compounds useful as inhibitors of protein kinases |
MXPA03011652A (es) * | 2001-06-15 | 2004-05-31 | Vertex Pharma | 5-(2-aminopirimidin-4-il) benzioxazoles como inhibidores de proteinas cinasa. |
EP1397142A4 (en) | 2001-06-19 | 2004-11-03 | Bristol Myers Squibb Co | PYRIMIDINE PHOSPHODIESTERASE (PDE) INHIBITORS 7 |
GB0115109D0 (en) | 2001-06-21 | 2001-08-15 | Aventis Pharma Ltd | Chemical compounds |
EP1408978A4 (en) | 2001-06-21 | 2005-07-13 | Ariad Pharma Inc | NOVEL PHENYLAMINO-PYRIMIDINES AND THEIR USE |
MXPA03011998A (es) * | 2001-06-23 | 2005-07-01 | Aventis Pharma Inc | Pirrolopirimidinas como inhibidores de protein cinasa. |
WO2003002544A1 (en) | 2001-06-26 | 2003-01-09 | Bristol-Myers Squibb Company | N-heterocyclic inhibitors of tnf-alpha expression |
JO3429B1 (ar) | 2001-08-13 | 2019-10-20 | Janssen Pharmaceutica Nv | مشتقات برميدينات مثبطة فيروس الايدز |
US6939874B2 (en) | 2001-08-22 | 2005-09-06 | Amgen Inc. | Substituted pyrimidinyl derivatives and methods of use |
US7115617B2 (en) | 2001-08-22 | 2006-10-03 | Amgen Inc. | Amino-substituted pyrimidinyl derivatives and methods of use |
US6433018B1 (en) * | 2001-08-31 | 2002-08-13 | The Research Foundation Of State University Of New York | Method for reducing hypertrophy and ischemia |
US7070996B2 (en) * | 2001-08-31 | 2006-07-04 | Rigel Pharmaceuticals, Inc. | Production of cultured human mast cells and basophils for high throughput small molecule drug discovery |
JP2005506982A (ja) * | 2001-09-10 | 2005-03-10 | スージェン・インコーポレーテッド | キナーゼ阻害剤としての3−(4,5,6,7−テトラヒドロインドール−2−イルメチリデン)−2−インドリノン誘導体 |
WO2003030909A1 (en) | 2001-09-25 | 2003-04-17 | Bayer Pharmaceuticals Corporation | 2- and 4-aminopyrimidines n-substtituded by a bicyclic ring for use as kinase inhibitors in the treatment of cancer |
WO2003026666A1 (en) | 2001-09-26 | 2003-04-03 | Bayer Pharmaceuticals Corporation | 2-phenylamino-4- (5-pyrazolylamino)-pyrimidine derivatives as kinase inhibitors, in particular, as src kinase inhibitors |
WO2003040141A1 (en) | 2001-09-28 | 2003-05-15 | Bayer Pharmaceuticals Corporation | Oxazolyl-phenyl-2,4-diamino-pyrimidine compounds and methods for treating hyperproliferative disorders |
WO2003032994A2 (de) | 2001-10-17 | 2003-04-24 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | 5-substituierte 4-amino-2-phenylamino-pyrimidinderivate und ihre verwendung als beta-amyloid modulatoren |
ES2314106T3 (es) | 2001-10-17 | 2009-03-16 | BOEHRINGER INGELHEIM PHARMA GMBH & CO.KG | Derivados de pirimidina, agentes farmaceuticos que contiene dichos compuestos, uso y metodo para su obtencion. |
US6897208B2 (en) * | 2001-10-26 | 2005-05-24 | Aventis Pharmaceuticals Inc. | Benzimidazoles |
EP1473289B1 (en) | 2001-11-28 | 2009-08-05 | Btg International Limited | Preventives or remedies for alzheimer's disease or amyloid protein fibrosis inhibitors containing nitrogen-containing heteroaryl compounds |
GT200200234A (es) | 2001-12-06 | 2003-06-27 | Compuestos cristalinos novedosos | |
SE0104140D0 (sv) | 2001-12-07 | 2001-12-07 | Astrazeneca Ab | Novel Compounds |
US20030158195A1 (en) * | 2001-12-21 | 2003-08-21 | Cywin Charles L. | 1,6 naphthyridines useful as inhibitors of SYK kinase |
AU2002367172A1 (en) * | 2001-12-21 | 2003-07-15 | Bayer Pharmaceuticals Corporation | 2,4-diamino-pyrimidine derivative compounds as inhibitors of prolylpeptidase, inducers of apoptosis and cancer treatment agents |
EP1470121B1 (en) | 2002-01-23 | 2012-07-11 | Bayer HealthCare LLC | Pyrimidine derivatives as rho-kinase inhibitors |
TWI329105B (en) * | 2002-02-01 | 2010-08-21 | Rigel Pharmaceuticals Inc | 2,4-pyrimidinediamine compounds and their uses |
US6998391B2 (en) * | 2002-02-07 | 2006-02-14 | Supergen.Inc. | Method for treating diseases associated with abnormal kinase activity |
WO2003066601A1 (en) | 2002-02-08 | 2003-08-14 | Smithkline Beecham Corporation | Pyrimidine compounds |
ATE365165T1 (de) | 2002-03-01 | 2007-07-15 | Smithkline Beecham Corp | Diaminopyrimidine und deren verwendung als angiogenesehemmer |
US7288547B2 (en) | 2002-03-11 | 2007-10-30 | Schering Ag | CDK-inhibitory 2-heteroaryl-pyrimidines, their production and use as pharmaceutical agents |
EP1483260A1 (de) | 2002-03-11 | 2004-12-08 | Schering Aktiengesellschaft | Cdk inhibitorische 2-heteroaryl-pyrimidine, deren herstellung und verwendung als arzneimittel |
GB0206215D0 (en) | 2002-03-15 | 2002-05-01 | Novartis Ag | Organic compounds |
WO2004039359A2 (en) | 2002-05-06 | 2004-05-13 | Bayer Pharmaceuticals Corporation | Use of pyrimidine derivates for the manifacture of a medicament for the treatment of hyper-proliferative disorders |
AU2003231231A1 (en) | 2002-05-06 | 2003-11-11 | Bayer Pharmaceuticals Corporation | Pyridinyl amino pyrimidine derivatives useful for treating hyper-proliferative disorders |
AR039540A1 (es) | 2002-05-13 | 2005-02-23 | Tibotec Pharm Ltd | Compuestos microbicidas con contenido de pirimidina o triazina |
EP1507779A1 (en) * | 2002-05-30 | 2005-02-23 | Vertex Pharmaceuticals Incorporated | Inhibitors of jak and cdk2 protein kinases |
EP1515964A1 (en) | 2002-06-14 | 2005-03-23 | ALTANA Pharma AG | Substituted diaminopyrimidines |
PL374963A1 (en) | 2002-06-17 | 2005-11-14 | Smithkline Beecham Corporation | Chemical process |
ES2373226T3 (es) | 2002-06-28 | 2012-02-01 | Astellas Pharma Inc. | Derivado de diaminopirimidincarboxamida. |
US6758434B2 (en) * | 2002-07-03 | 2004-07-06 | Kimberly-Clark Worldwide, Inc. | Dispenser for multiple rolls of sheet material |
CN103169708B (zh) | 2002-07-29 | 2018-02-02 | 里格尔药品股份有限公司 | 用2,4‑嘧啶二胺化合物治疗或者预防自体免疫性疾病的方法 |
WO2004014384A2 (en) | 2002-08-13 | 2004-02-19 | Warner-Lambert Company Llc | Cyclic compounds containing zinc binding groups as matrix metalloproteinase inhibitors |
WO2004016597A2 (en) * | 2002-08-14 | 2004-02-26 | Vertex Pharmaceuticals Incorporated | Protein kinase inhibitors and uses thereof |
DE10243291B4 (de) * | 2002-09-18 | 2015-04-30 | Mann + Hummel Gmbh | Ventil, insbesondere für den Ölkreislauf einer Brennkraftmaschine |
CA2506772A1 (en) | 2002-11-01 | 2004-05-21 | Vertex Pharmaceuticals Incorporated | Compositions useful as inhibitors of jak and other protein kinases |
ATE371656T1 (de) | 2002-11-04 | 2007-09-15 | Vertex Pharma | Heteroaryl-pyrimidinderivate als jak-inhibitoren |
AU2003286895A1 (en) | 2002-11-05 | 2004-06-07 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of jak and other protein kinases |
GB0226583D0 (en) | 2002-11-14 | 2002-12-18 | Cyclacel Ltd | Compounds |
GB0226582D0 (en) | 2002-11-14 | 2002-12-18 | Cyclacel Ltd | Anti-viral compounds |
TWI335913B (en) * | 2002-11-15 | 2011-01-11 | Vertex Pharma | Diaminotriazoles useful as inhibitors of protein kinases |
WO2004046112A2 (en) | 2002-11-21 | 2004-06-03 | Pfizer Products Inc. | 3-amino-piperidine derivatives and processes for their preparation |
PL378246A1 (pl) | 2002-11-26 | 2006-03-20 | Pfizer Products Inc. | Sposób leczenia odrzucania przeszczepu |
MXPA05005547A (es) | 2002-11-28 | 2005-07-26 | Schering Ag | Pirimidinas inhibidoras de chk, pdk y akt, su produccion y uso como agentes farmaceuticos. |
AU2002350719A1 (en) | 2002-11-29 | 2004-06-23 | Janssen Pharmaceutica N.V. | Pharmaceutical compositions comprising a basic respectively acidic drug compound, a surfactant and a physiologically tolerable water-soluble acid respectively base |
AU2003289330A1 (en) | 2002-12-13 | 2004-07-09 | Kyowa Hakko Kogyo Co., Ltd. | Preventives and/or remedies for central diseases |
US7226919B2 (en) | 2002-12-18 | 2007-06-05 | Vertex Pharmaceuticals Inc. | Compositions useful as inhibitors of protein kinases |
US7098332B2 (en) | 2002-12-20 | 2006-08-29 | Hoffmann-La Roche Inc. | 5,8-Dihydro-6H-pyrido[2,3-d]pyrimidin-7-ones |
UA80767C2 (en) | 2002-12-20 | 2007-10-25 | Pfizer Prod Inc | Pyrimidine derivatives for the treatment of abnormal cell growth |
US20040242613A1 (en) | 2003-01-30 | 2004-12-02 | Boehringer Ingelheim Pharmaceuticals, Inc. | Pyrimidine derivatives useful as inhibitors of PKC-theta |
CL2004000192A1 (es) | 2003-02-07 | 2005-03-18 | Janssen Pharmaceutica Nv | Uso de compuestos derivados de 2-aminopirimidina para preparar un medicamento para la prevencion de una infeccion por vih relaciones sexuales o un contacto intimo en la pareja. |
ATE433447T1 (de) | 2003-02-20 | 2009-06-15 | Smithkline Beecham Corp | Pyrimiidinverbindungen |
CL2004000306A1 (es) | 2003-02-20 | 2005-04-08 | Tibotec Pharm Ltd | Compuestos derivados de pirimidina sustituidas con indano; proceso para su preparacion; composicion farmaceutica que lo comprende; combinacion farmaceutica; y su uso para el tratamiento o profilaxis de una enfermedad infecciosa. |
GB0305929D0 (en) | 2003-03-14 | 2003-04-23 | Novartis Ag | Organic compounds |
WO2004092154A1 (en) * | 2003-04-03 | 2004-10-28 | Vertex Pharmaceuticals Incorporated | Compositions useful as inhibitors of protein kinases |
MXPA05011523A (es) | 2003-04-30 | 2006-01-23 | Inst For Pharm Discovery Inc | Heteroarilos sustituidos como inhibidores de proteinas de tirosina fosfatasas. |
GB0311274D0 (en) | 2003-05-16 | 2003-06-18 | Astrazeneca Ab | Chemical compounds |
GB0311276D0 (en) | 2003-05-16 | 2003-06-18 | Astrazeneca Ab | Chemical compounds |
US7915293B2 (en) | 2003-05-30 | 2011-03-29 | Rigel Pharmaceuticals, Inc. | Ubiquitin ligase inhibitors |
CA2531401A1 (en) | 2003-07-10 | 2005-01-27 | Neurogen Corporation | Substituted heterocyclic diarylamine analogues |
CN100549014C (zh) | 2003-07-16 | 2009-10-14 | 詹森药业有限公司 | 作为糖原合酶激酶3抑制剂的三唑并嘧啶衍生物 |
ATE370142T1 (de) | 2003-07-16 | 2007-09-15 | Janssen Pharmaceutica Nv | Triazolopyrimidinderivate als inhibitoren von glycogensynthasekinase-3 |
CN1826328A (zh) | 2003-07-22 | 2006-08-30 | 神经能质公司 | 经取代的吡啶-2-基胺类似物 |
US7442698B2 (en) * | 2003-07-24 | 2008-10-28 | Amgen Inc. | Substituted heterocyclic compounds and methods of use |
EP1651599A4 (en) | 2003-07-24 | 2008-09-24 | Merck & Co Inc | TYROSINE KINASE INHIBITORS |
AU2004261484A1 (en) | 2003-07-30 | 2005-02-10 | Cyclacel Limited | 2-aminophenyl-4-phenylpyrimidines as kinase inhibitors |
CA2533377C (en) | 2003-07-30 | 2012-11-27 | Rigel Pharmaceuticals, Inc. | Methods of treating or preventing autoimmune diseases with 2,4-pyrimidinediamine compounds |
WO2005013996A2 (en) | 2003-08-07 | 2005-02-17 | Rigel Pharmaceuticals, Inc. | 2,4-pyrimidinediamine compounds and uses as anti-proliferative agents |
OA13235A (en) | 2003-08-14 | 2006-12-13 | Pfizer | Piperazine derivatives for the treatment of HIV infections. |
CA2533320A1 (en) | 2003-08-15 | 2006-02-24 | Novartis Ag | 2, 4-pyrimidinediamines useful in the treatment of neoplastic diseases, inflammatory and immune system disorders |
TWI339206B (en) | 2003-09-04 | 2011-03-21 | Vertex Pharma | Compositions useful as inhibitors of protein kinases |
WO2005028467A1 (en) | 2003-09-15 | 2005-03-31 | Anadys Pharmaceuticals, Inc. | Antibacterial 3,5-diaminopiperidine-substitute aromatic and heteroaromatic compounds |
GB0321710D0 (en) | 2003-09-16 | 2003-10-15 | Novartis Ag | Organic compounds |
US20070105839A1 (en) | 2003-09-18 | 2007-05-10 | Patricia Imbach | 2, 4-Di (phenylamino) pyrimidines useful in the treatment of proliferative disorders |
WO2005027848A2 (en) | 2003-09-19 | 2005-03-31 | Barnes-Jewish Hospital | Methods for screening osteogenic compounds targeting syk kinase and/or vav3 and uses of syk modulators and/or vav modulators |
AP2006003517A0 (en) | 2003-09-25 | 2006-02-28 | Janssen Pharmaceutica Nv | Hiv replication purine derivatives. |
OA13266A (en) | 2003-10-03 | 2007-01-31 | Pfizer | Imidazopyridine substituted tropane derivatives with CCR5 receptor antagonist activity for the treatment of HIV and inflammation. |
DE10349423A1 (de) | 2003-10-16 | 2005-06-16 | Schering Ag | Sulfoximinsubstituierte Parimidine als CDK- und/oder VEGF-Inhibitoren, deren Herstellung und Verwendung als Arzneimittel |
AU2004292773A1 (en) | 2003-11-28 | 2005-06-09 | Novartis Ag | Diaryl urea derivatives in the treatment of protein kinase dependent diseases |
MY141255A (en) | 2003-12-11 | 2010-03-31 | Memory Pharm Corp | Phosphodiesterase 4 inhibitors, including n-substituted diarylamine analogs |
US7511137B2 (en) | 2003-12-19 | 2009-03-31 | Rigel Pharmaceuticals, Inc. | Stereoisomers and stereoisomeric mixtures of 1-(2,4-pyrimidinediamino)-2-cyclopentanecarboxamide synthetic intermediates |
MXPA06007640A (es) | 2004-01-12 | 2007-04-17 | Cytopia Res Pty Ltd | Inhibidores de quinasa selectivos. |
GB0402653D0 (en) | 2004-02-06 | 2004-03-10 | Cyclacel Ltd | Compounds |
PL1713806T3 (pl) | 2004-02-14 | 2013-09-30 | Irm Llc | Związki i kompozycje jako inhibitory kinaz białkowych |
US7745625B2 (en) * | 2004-03-15 | 2010-06-29 | Bristol-Myers Squibb Company | Prodrugs of piperazine and substituted piperidine antiviral agents |
WO2005107760A1 (en) | 2004-04-30 | 2005-11-17 | Irm Llc | Compounds and compositions as inducers of keratinocyte differentiation |
CA2566531A1 (en) | 2004-05-18 | 2005-12-15 | Rigel Pharmaceuticals, Inc. | Cycloalkyl substituted pyrimidinediamine compounds and their uses |
EP1598343A1 (de) | 2004-05-19 | 2005-11-23 | Boehringer Ingelheim International GmbH | 2-Arylaminopyrimidine als PLK Inhibitoren |
US20060047135A1 (en) * | 2004-08-30 | 2006-03-02 | Chadwick Scott T | Process for preparing chloromethyl di-tert-butylphosphate |
WO2006028833A1 (en) | 2004-09-01 | 2006-03-16 | Rigel Pharmaceuticals, Inc. | Synthesis of 2,4-pyrimidinediamine compounds |
WO2006034872A1 (de) | 2004-09-29 | 2006-04-06 | Bayer Schering Pharma Aktiengesellschaft | Substituierte 2-anilinopyrimidine als zellzyklus -kinase oder rezeptortyrosin-kinase inhibitoren, deren herstellung und verwendung als arzneimittel |
AU2005288865B2 (en) | 2004-09-30 | 2012-07-19 | Janssen Sciences Ireland Uc | HIV inhibiting 5-carbo- or heterocyclic substituted pyrimidines |
JP2008518967A (ja) * | 2004-10-29 | 2008-06-05 | ライジェル ファーマシューティカルズ, インコーポレイテッド | Sykキナーゼに対する活性を有する置換ピリジン |
CA2584295C (en) | 2004-11-24 | 2014-08-26 | Rigel Pharmaceuticals, Inc. | Spiro-2, 4-pyrimidinediamine compounds and their uses |
ATE519759T1 (de) | 2004-12-30 | 2011-08-15 | Exelixis Inc | Pyrimidinderivate als kinasemodulatoren und anwendungsverfahren |
ES2337496T3 (es) | 2005-01-19 | 2010-04-26 | Rigel Pharmaceuticals, Inc. | Profarmacos de compuestos de 2,4-pirimidindiamina y sus usos. |
US20060270694A1 (en) | 2005-05-03 | 2006-11-30 | Rigel Pharmaceuticals, Inc. | JAK kinase inhibitors and their uses |
US20060251285A1 (en) | 2005-05-05 | 2006-11-09 | Mrs. Yen-Chen Chan | [surge-proof damper] |
JP5225079B2 (ja) | 2005-06-08 | 2013-07-03 | ライジェル ファーマシューティカルズ, インコーポレイテッド | Jak経路の阻害のための組成物および方法 |
US20070203161A1 (en) * | 2006-02-24 | 2007-08-30 | Rigel Pharmaceuticals, Inc. | Compositions and methods for inhibition of the jak pathway |
US7576053B2 (en) | 2005-06-13 | 2009-08-18 | Rigel Pharmaceuticals, Inc. | Methods and compositions for treating degenerative bone disorders |
MX2008000574A (es) | 2005-07-11 | 2008-03-14 | Sanofi Aventis | Nuevos derivados de 2,4-dianilinopirimidinas, la preparacion de los mismos, su uso como medicamentos, composiciones farmaceuticas y, en particular, como inhibidores ikk. |
PT1951684T (pt) | 2005-11-01 | 2016-10-13 | Targegen Inc | Inibidores de cinases de tipo biaril-meta-pirimidina |
US7713987B2 (en) * | 2005-12-06 | 2010-05-11 | Rigel Pharmaceuticals, Inc. | Pyrimidine-2,4-diamines and their uses |
UA89123C2 (ru) | 2005-12-21 | 2009-12-25 | Пфайзер Продактс Инк. | Производные пиримидина для лечения абнормального роста клеток |
TW200736232A (en) | 2006-01-26 | 2007-10-01 | Astrazeneca Ab | Pyrimidine derivatives |
WO2007085540A1 (en) | 2006-01-27 | 2007-08-02 | Glaxo Group Limited | 1h-indaz0l-4-yl-2 , 4-pyrimidinediamine derivatives |
SI1984357T1 (sl) * | 2006-02-17 | 2014-02-28 | Rigel Pharmaceuticals, Inc. | Spojine 2,4-pirimidindiamina za zdravljenje ali preventivo avtoimunih bolezni |
JP2009528295A (ja) | 2006-02-24 | 2009-08-06 | ライジェル ファーマシューティカルズ, インコーポレイテッド | Jak経路の阻害のための組成物および方法 |
CA2673125C (en) | 2006-10-19 | 2015-04-21 | Rigel Pharmaceuticals, Inc. | Compositions and methods for inhibition of the jak pathway |
US8163902B2 (en) * | 2006-11-21 | 2012-04-24 | Rigel Pharmaceuticals, Inc. | Prodrugs of 2,4-pyrimidinediamine compounds and their uses |
CN101563327A (zh) | 2006-12-19 | 2009-10-21 | 健泰科生物技术公司 | 嘧啶类激酶抑制剂 |
TW200902010A (en) | 2007-01-26 | 2009-01-16 | Smithkline Beecham Corp | Anthranilamide inhibitors of aurora kinase |
US7947698B2 (en) | 2007-03-23 | 2011-05-24 | Rigel Pharmaceuticals, Inc. | Compositions and methods for inhibition of the JAK pathway |
US7834024B2 (en) | 2007-03-26 | 2010-11-16 | Rigel Pharmaceuticals, Inc. | Compositions and methods for inhibition of the JAK pathway |
CA2693594A1 (en) * | 2007-07-17 | 2009-01-22 | Rigel Pharmaceuticals, Inc. | Cyclic amine substituted pyrimidinediamines as pkc inhibitors |
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