ZA200404223B - Pyrimidine derivatives as modulars of insuline-like growth factor-1 receptor (IGF-I). - Google Patents

Pyrimidine derivatives as modulars of insuline-like growth factor-1 receptor (IGF-I). Download PDF

Info

Publication number: ZA200404223B
Authority: ZA; South Africa
Prior art keywords: pharmaceutically acceptable; compound; solvate; formula; ring
Prior art date: 2001-12-07

Application number

ZA200404223A

Other languages

English (en)

Inventor

Bernard Barlaam

Andrew Thomas

Andrew Pape

Original Assignee

Astrazeneca Ab

Priority date (The priority date 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 date listed.)

2001-12-07

Filing date

2004-05-28

Publication date

2005-08-29

2004-05-28 Application filed by Astrazeneca Ab filed Critical Astrazeneca Ab

2005-08-29 Publication of ZA200404223B publication Critical patent/ZA200404223B/en

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108090000723 Insulin-Like Growth Factor I Proteins 0.000 title description 16
102000004218 Insulin-Like Growth Factor I Human genes 0.000 title description 4
230000012010 growth Effects 0.000 title description 3
229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 title description 2
150000003230 pyrimidines Chemical class 0.000 title description 2
-1 amino, hydroxyl Chemical group 0.000 claims description 162
229910052757 nitrogen Inorganic materials 0.000 claims description 68
125000001424 substituent group Chemical group 0.000 claims description 63
150000001875 compounds Chemical class 0.000 claims description 58
229910052736 halogen Inorganic materials 0.000 claims description 44
150000002367 halogens Chemical class 0.000 claims description 44
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 40
239000001257 hydrogen Substances 0.000 claims description 39
229910052739 hydrogen Inorganic materials 0.000 claims description 39
125000005842 heteroatom Chemical group 0.000 claims description 35
125000004433 nitrogen atom Chemical group N* 0.000 claims description 35
150000003839 salts Chemical class 0.000 claims description 34
239000012453 solvate Substances 0.000 claims description 34
150000002431 hydrogen Chemical class 0.000 claims description 33
125000000623 heterocyclic group Chemical group 0.000 claims description 31
125000001072 heteroaryl group Chemical group 0.000 claims description 29
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 28
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 28
229910052760 oxygen Inorganic materials 0.000 claims description 28
239000001301 oxygen Chemical group 0.000 claims description 28
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125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 23
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 22
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 21
239000005864 Sulphur Chemical group 0.000 claims description 21
125000003226 pyrazolyl group Chemical group 0.000 claims description 21
206010028980 Neoplasm Diseases 0.000 claims description 19
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Classifications

- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/48—Two nitrogen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—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 linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—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
- 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
- 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

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Public Health (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmacology & Pharmacy (AREA)
Veterinary Medicine (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Hematology (AREA)
Oncology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (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)

ZA200404223A 2001-12-07 2004-05-28 Pyrimidine derivatives as modulars of insuline-like growth factor-1 receptor (IGF-I). ZA200404223B (en)

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SE0104140A SE0104140D0 (sv)	2001-12-07	2001-12-07	Novel Compounds

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ZA200404223A ZA200404223B (en)	2001-12-07	2004-05-28	Pyrimidine derivatives as modulars of insuline-like growth factor-1 receptor (IGF-I).

Country Status (32)

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US (3)	US7521453B2 (fr)
EP (1)	EP1456182B1 (fr)
JP (1)	JP4347051B2 (fr)
KR (1)	KR100930558B1 (fr)
CN (1)	CN1289486C (fr)
AR (1)	AR037736A1 (fr)
AT (1)	ATE425150T1 (fr)
AU (1)	AU2002365864B2 (fr)
BR (1)	BR0214605A (fr)
CA (1)	CA2467838C (fr)
CO (1)	CO5590919A2 (fr)
CY (1)	CY1109101T1 (fr)
DE (1)	DE60231542D1 (fr)
DK (1)	DK1456182T3 (fr)
EG (1)	EG24930A (fr)
ES (1)	ES2323125T3 (fr)
HU (1)	HUP0401855A3 (fr)
IL (2)	IL162376A0 (fr)
IS (1)	IS7294A (fr)
MX (1)	MXPA04005347A (fr)
MY (1)	MY135705A (fr)
NO (1)	NO327502B1 (fr)
NZ (1)	NZ533130A (fr)
PL (1)	PL369528A1 (fr)
PT (1)	PT1456182E (fr)
RU (1)	RU2317291C2 (fr)
SE (1)	SE0104140D0 (fr)
SI (1)	SI1456182T1 (fr)
TW (1)	TWI324152B (fr)
UA (1)	UA78259C2 (fr)
WO (1)	WO2003048133A1 (fr)
ZA (1)	ZA200404223B (fr)

Families Citing this family (73)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
SE0104140D0 (sv) *	2001-12-07	2001-12-07	Astrazeneca Ab	Novel Compounds
TWI329105B (en)	2002-02-01	2010-08-21	Rigel Pharmaceuticals Inc	2,4-pyrimidinediamine compounds and their uses
ATE451104T1 (de)	2002-07-29	2009-12-15	Rigel Pharmaceuticals Inc	Verfahren zur behandlung oder pruvention von autoimmunkrankheiten mit 2,4-pyrimidindiamin- verbindungen
US7504396B2 (en)	2003-06-24	2009-03-17	Amgen Inc.	Substituted heterocyclic compounds and methods of use
US7442698B2 (en)	2003-07-24	2008-10-28	Amgen Inc.	Substituted heterocyclic compounds and methods of use
PL1656372T3 (pl)	2003-07-30	2013-08-30	Rigel Pharmaceuticals Inc	Związki 2,4-pirymidynodiaminy do stosowania w leczeniu lub zapobieganiu chorobom autoimmunologicznym
JP4741491B2 (ja) *	2003-08-07	2011-08-03	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	抗増殖剤としての２，４−ピリミジンジアミン化合物および使用
TW200530238A (en) *	2003-10-15	2005-09-16	Osi Pharm Inc	Imidazopyrazine tyrosine kinase inhibitors
ES2328820T3 (es)	2003-10-17	2009-11-18	Astrazeneca Ab	Derivados de 4-(pirazol-3-ilamino)pirimidina para uso en el tratamiento de cancer.
MY141220A (en) *	2003-11-17	2010-03-31	Astrazeneca Ab	Pyrazole derivatives as inhibitors of receptor tyrosine kinases
PT1732898E (pt)	2004-03-12	2008-04-07	Analytecon Sa	Derivados de tetrahidroisoquinolina e tetrahidrobenzazepina como inibidores igf-1r
CA2559866A1 (fr) *	2004-03-31	2005-10-20	Exelixis, Inc.	Modulateurs de kinases de lymphomes anaplasiques (alk) et methodes d'utilisation
PL1740591T3 (pl)	2004-04-02	2009-11-30	Osi Pharm Inc	Heterobicykliczne inhibitory kinazy białkowej podstawione 6,6-bicyklicznym pierścieniem
DE102004022897A1 (de) *	2004-05-10	2005-12-08	Bayer Cropscience Ag	Azinyl-imidazoazine
AR053090A1 (es)	2004-07-20	2007-04-25	Osi Pharm Inc	Imidazotriazinas como inhibidores de proteina quinasas y su uso para la preparacion de medicamentos
US7557207B2 (en)	2004-11-24	2009-07-07	Rigel Pharmaceuticals, Inc.	Spiro 2,4-pyrimidinediamine compounds and their uses
US8211929B2 (en) *	2004-12-30	2012-07-03	Exelixis, Inc.	Pyrimidine derivatives as kinase modulators and method of use
EP1856135B1 (fr)	2005-01-19	2009-12-09	Rigel Pharmaceuticals, Inc.	Promedicaments de composes de 2,4-pyrimidinediamine et leurs utilisations
RU2415852C2 (ru) *	2005-02-04	2011-04-10	Астразенека Аб	Производные пиразолиламинопиридина, пригодные в качестве ингибиторов киназы
CN101155800B (zh)	2005-02-04	2012-05-23	阿斯利康(瑞典)有限公司	可用作激酶抑制剂的吡唑基氨基吡啶衍生物
MX2007009843A (es) *	2005-02-16	2007-08-23	Astrazeneca Ab	Compuestos quimicos.
GB0507347D0 (en) *	2005-04-12	2005-05-18	Astrazeneca Ab	Chemical compounds
WO2006115452A1 (fr) *	2005-04-27	2006-11-02	Astrazeneca Ab	Utilisation des derives de la pyrazolyl-pyrimidine dans le traitement de la douleur
MX2007014328A (es) *	2005-05-16	2008-02-12	Astrazeneca Ab	Compuestos quimicos.
CA2608367C (fr)	2005-06-08	2014-08-19	Rigel Pharmaceuticals, Inc.	Compositions et procedes d'inhibition de la voie jak
US20070203161A1 (en)	2006-02-24	2007-08-30	Rigel Pharmaceuticals, Inc.	Compositions and methods for inhibition of the jak pathway
US7566721B2 (en) *	2005-08-08	2009-07-28	Osi Pharmaceuticals, Inc.	Substituted thienol[2,3-d]pyrimidines as kinase inhibitors
AR056471A1 (es)	2005-08-24	2007-10-10	Wyeth Corp	Formulaciones de acetato de bazedoxifeno
ES2374450T3 (es)	2005-09-20	2012-02-16	OSI Pharmaceuticals, LLC	Marcadores biológicos predictivos de respuesta anticancerígena para inhibidores de cinasa del receptor del factor de crecimiento 1 similar a insulina.
ES2391783T3 (es) *	2005-10-28	2012-11-29	Astrazeneca Ab	Derivados de 4-(3-aminopirazol)pirimidina para su uso como agentes inhibidores de las tirosina cinasas en el tratamiento del cáncer
AR057960A1 (es)	2005-12-02	2007-12-26	Osi Pharm Inc	Inhibidores de proteina quinasa biciclicos
US8575164B2 (en) *	2005-12-19	2013-11-05	OSI Pharmaceuticals, LLC	Combination cancer therapy
MY147856A (en) *	2006-06-09	2013-01-31	Novartis Ag	Stabilized insulin-like growth factor polypeptides
CN101506176A (zh) *	2006-06-15	2009-08-12	贝林格尔.英格海姆国际有限公司	2-苯胺基-4-氨基亚烷基氨基嘧啶
WO2008001070A1 (fr) *	2006-06-30	2008-01-03	Astrazeneca Ab	Dérivés de pyrimidine utiles dans le traitement du cancer
WO2008005538A2 (fr) *	2006-07-05	2008-01-10	Exelixis, Inc.	Procédés d'utilisation de modulateurs de kinase igf1r et abl
WO2008129255A1 (fr) *	2007-04-18	2008-10-30	Astrazeneca Ab	Dérivés de 5-aminopyrazol-3-yl-3h-imidazo[4,5-b]pyridine et leur utilisation pour le traitement du cancer
UA99459C2 (en) *	2007-05-04	2012-08-27	Астразенека Аб	9-(pyrazol-3-yl)- 9h-purine-2-amine and 3-(pyraz0l-3-yl)-3h-imidazo[4,5-b]pyridin-5-amine derivatives and their use for the treatment of cancer
US20100137398A1 (en) *	2007-05-04	2010-06-03	Novartis Ag	Use of hdac inhibitors for the treatment of gastrointestinal cancers
US8178091B2 (en)	2007-05-21	2012-05-15	University Of Washington	Compositions and methods for the treatment of respiratory disorders
WO2009019518A1 (fr) *	2007-08-09	2009-02-12	Astrazeneca Ab	Composés de pyrimidine ayant un effet inhibiteur du fgfr
WO2009091939A1 (fr) *	2008-01-18	2009-07-23	Osi Pharmaceuticals, Inc.	Dérivés d'imidazopyrazinol pour le traitement des cancers
WO2009143051A1 (fr) *	2008-05-19	2009-11-26	Osi Pharmaceuticals, Inc.	Imidazopyrazines et imidazotriazines substituées
CN102119157A (zh) *	2008-06-11	2011-07-06	阿斯利康(瑞典)有限公司	用于治疗癌症和骨髓增生性疾病的三环2，4-二氨基-l，3，5-三嗪衍生物
DE102008041214A1 (de)	2008-08-13	2010-02-18	Bayer Cropscience Ag	N-substituierte Azinylakyl-azincarboxamide und deren Analoge
EP2346859A1 (fr) *	2008-09-30	2011-07-27	AstraZeneca AB	Inhibiteurs hétérocycliques de la kinase jak
EP2400985A2 (fr)	2009-02-25	2012-01-04	OSI Pharmaceuticals, LLC	Thérapie anti-cancer combinée
WO2010099137A2 (fr)	2009-02-26	2010-09-02	Osi Pharmaceuticals, Inc.	Procédés in situ pour surveiller l'état emt de cellules tumorales in vivo
EP2401614A1 (fr)	2009-02-27	2012-01-04	OSI Pharmaceuticals, LLC	Méthodes d'identification d'agents qui inhibent les cellules cancéreuses mésenchymateuses ou leur formation
WO2010099364A2 (fr)	2009-02-27	2010-09-02	Osi Pharmaceuticals, Inc.	Méthodes d'identification d'agents qui inhibent les cellules cancéreuses mésenchymateuses ou leur formation
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
CA2752826A1 (fr)	2009-04-20	2010-10-28	OSI Pharmaceuticals, LLC	Preparation de c-pyrazine-methylamines
WO2010129740A1 (fr) *	2009-05-07	2010-11-11	Osi Pharmaceuticals, Inc.	Utilisation d'osi-906 dans le traitement du carcinome adrénocortical
US20100316639A1 (en)	2009-06-16	2010-12-16	Genentech, Inc.	Biomarkers for igf-1r inhibitor therapy
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
JP2013527748A (ja)	2010-03-03	2013-07-04	オーエスアイ・ファーマシューティカルズ，エルエルシー	インスリン様増殖因子１受容体キナーゼ阻害剤に対する抗癌反応の予測に役立つ生物学的マーカー
JP2013522215A (ja)	2010-03-09	2013-06-13	オーエスアイ・ファーマシューティカルズ，エルエルシー	組合わせ抗癌療法
CN102970867A (zh)	2010-03-18	2013-03-13	拜耳知识产权有限责任公司	作为活性剂对抗非生物植物应激的芳基和杂芳基磺酰胺
AU2011254550B2 (en)	2010-05-21	2013-11-07	Noviga Research Ab	Novel pyrimidine derivatives
US8546443B2 (en) *	2010-12-21	2013-10-01	Boehringer Ingelheim International Gmbh	Benzylic oxindole pyrimidines
EP2671082B1 (fr)	2011-02-02	2020-01-15	Amgen Inc.	Méthodes et compositions associées à l'inhibition d'igf-1r
US20120214830A1 (en)	2011-02-22	2012-08-23	OSI Pharmaceuticals, LLC	Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors in hepatocellular carcinoma
JP5886411B2 (ja)	2011-03-24	2016-03-16	ノビガ・リサーチ・エービーＮｏｖｉｇａＲｅｓｅａｒｃｈＡＢ	新規のピリミジン誘導体
US9096691B2 (en)	2011-04-13	2015-08-04	Eastman Chemical Company	Cellulose ester optical films
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
ES2723827T3 (es)	2011-11-11	2019-09-02	Univ Duke	Terapia de combinación de fármacos para el tratamiento de tumores sólidos
WO2013152252A1 (fr)	2012-04-06	2013-10-10	OSI Pharmaceuticals, LLC	Polythérapie antinéoplasique
US8980259B2 (en)	2012-07-20	2015-03-17	Novartis Ag	Combination therapy
CA2941010A1 (fr)	2013-02-26	2014-09-04	Triact Therapeutics, Inc.	Cancerotherapie
WO2015035410A1 (fr)	2013-09-09	2015-03-12	Triact Therapeutic, Inc.	Traitement du cancer
WO2017129763A1 (fr)	2016-01-28	2017-08-03	INSERM (Institut National de la Santé et de la Recherche Médicale)	Méthodes et compositions pharmaceutiques pour le traitement du cancer de l'estomac à cellules en bague à chaton
CN115124475B (zh) *	2022-07-11	2023-11-10	贵阳学院	一种嘧啶衍生物及其制备方法和用途
WO2024153237A1 (fr) *	2023-01-19	2024-07-25	北京普祺医药科技股份有限公司	Inhibiteurs de tyrosine kinase igf-1r, composition pharmaceutique et leur utilisation

Family Cites Families (41)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB1417402A (en) *	1972-03-30	1975-12-10	Boots Co Ltd	Pharmacologically active anilinobenzothiazoles
DE2426180A1 (de)	1974-05-29	1975-12-18	Bayer Ag	Verfahren zum faerben von polyurethankunststoffen
US4485284A (en) *	1982-01-11	1984-11-27	Advanced Moisture Technology, Inc.	Apparatus and process for microwave moisture analysis
HU206337B (en)	1988-12-29	1992-10-28	Mitsui Petrochemical Ind	Process for producing pyrimidine derivatives and pharmaceutical compositions
US5521184A (en) *	1992-04-03	1996-05-28	Ciba-Geigy Corporation	Pyrimidine derivatives and processes for the preparation thereof
CA2104053C (fr) *	1992-08-31	1999-04-13	Miguel A. Cacho	Procede automatique a lit fluidise
WO1997009325A1 (fr)	1995-09-01	1997-03-13	Signal Pharmaceuticals, Inc.	Carboxylates de pyrimidine, composes connexes et methodes de traitement des etats inflammatoires
US5935966A (en)	1995-09-01	1999-08-10	Signal Pharmaceuticals, Inc.	Pyrimidine carboxylates and related compounds and methods for treating inflammatory conditions
GB9523675D0 (en)	1995-11-20	1996-01-24	Celltech Therapeutics Ltd	Chemical compounds
JP2001517146A (ja) *	1997-03-27	2001-10-02	グラツトゲゼルシヤフトミツトベシユレンクテルハフツング	生産物の湿度を測定することにより、渦流流体層又は可動注入体内の顆粒化−、塊状化−、インスタント製品化−、コーティング−及び乾燥プロセス加工の監視及び／又は制御及び調整方法、並びに、前記方法を実施するためのエアエンジニアリング装置
US6247246B1 (en) *	1998-05-27	2001-06-19	Denver Instrument Company	Microwave moisture analyzer: apparatus and method
WO2000012485A1 (fr)	1998-08-29	2000-03-09	Astrazeneca Ab	Composes de pyrimidine
TR200101306T2 (tr)	1998-11-10	2001-10-22	Janssen Pharmaceutica N.V.	HİV Virüsünün çoğalmasını önleyen pirimidinler
US6337338B1 (en)	1998-12-15	2002-01-08	Telik, Inc.	Heteroaryl-aryl ureas as IGF-1 receptor antagonists
GB9828511D0 (en) *	1998-12-24	1999-02-17	Zeneca Ltd	Chemical compounds
DE19917785A1 (de) *	1999-04-20	2000-10-26	Bayer Ag	2,4-Diamino-pyrimidin-Derivate
GB9914258D0 (en)	1999-06-18	1999-08-18	Celltech Therapeutics Ltd	Chemical compounds
US6399780B1 (en) *	1999-08-20	2002-06-04	Cephalon, Inc.	Isomeric fused pyrrolocarbazoles and isoindolones
MXPA02003182A (es)	1999-09-24	2002-09-30	Janssen Pharmaceutica Nv	Composiciones antivirales.
US6455525B1 (en) *	1999-11-04	2002-09-24	Cephalon, Inc.	Heterocyclic substituted pyrazolones
AU2001237041B9 (en)	2000-02-17	2005-07-28	Amgen Inc.	Kinase inhibitors
GB0004887D0 (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
EP1282607B1 (fr)	2000-05-08	2015-11-11	Janssen Pharmaceutica NV	Promedicaments a base de pyrimidines inhibant la replication du vih
ATE327992T1 (de) *	2000-09-15	2006-06-15	Vertex Pharma	Pyrazolverbindungen als protein-kinasehemmer
US6610677B2 (en) *	2000-09-15	2003-08-26	Vertex Pharmaceuticals Incorporated	Pyrazole compounds useful as protein kinase inhibitors
US6660731B2 (en) *	2000-09-15	2003-12-09	Vertex Pharmaceuticals Incorporated	Pyrazole compounds useful as protein kinase inhibitors
US7473691B2 (en) *	2000-09-15	2009-01-06	Vertex Pharmaceuticals Incorporated	Pyrazole compounds useful as protein kinase inhibitors
US6613776B2 (en) *	2000-09-15	2003-09-02	Vertex Pharmaceuticals Incorporated	Pyrazole compounds useful as protein kinase inhibitors
BR0116493A (pt) *	2000-12-21	2003-09-30	Vertex Pharma	Compostos de pirazol úteis como inibidores de proteìna cinase
DE60226154T2 (de) *	2001-08-03	2009-05-20	Vertex Pharmaceuticals Inc., Cambridge	Von pyrazol abgeleitete kinaseinhibitoren und deren verwendung
DE60238620D1 (de) *	2001-08-03	2011-01-27	Vertex Pharma	Von pyrazol abgeleitete kinaseinhibitoren und deren verwendung
US6747461B2 (en) *	2001-10-25	2004-06-08	Pioneer Hi-Bred International, Inc.	Apparatus and method for monitoring drying of an agricultural porous medium such as grain or seed
SE0104140D0 (sv) *	2001-12-07	2001-12-07	Astrazeneca Ab	Novel Compounds
MY141220A (en) *	2003-11-17	2010-03-31	Astrazeneca Ab	Pyrazole derivatives as inhibitors of receptor tyrosine kinases
NZ555236A (en) *	2004-11-04	2010-10-29	Vertex Pharma	Pyrazolo[1,5-a]pyrimidines useful as inhibitors of protein kinases
MX2007009843A (es) *	2005-02-16	2007-08-23	Astrazeneca Ab	Compuestos quimicos.
CN101316843B (zh) *	2005-11-03	2013-01-02	顶点医药品公司	用作激酶抑制剂的氨基嘧啶
WO2008001070A1 (fr) *	2006-06-30	2008-01-03	Astrazeneca Ab	Dérivés de pyrimidine utiles dans le traitement du cancer
TW200823196A (en) *	2006-11-01	2008-06-01	Astrazeneca Ab	New use
TW200826937A (en) *	2006-11-01	2008-07-01	Astrazeneca Ab	New use

2001
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- 2002-12-03 CN CNB02827802XA patent/CN1289486C/zh not_active Expired - Fee Related
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- 2002-12-03 WO PCT/SE2002/002221 patent/WO2003048133A1/fr active Application Filing
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Also Published As

Publication number	Publication date
IL162376A (en)	2011-07-31
EP1456182B1 (fr)	2009-03-11
HUP0401855A3 (en)	2008-06-30
CO5590919A2 (es)	2005-12-30
UA78259C2 (en)	2007-03-15
DE60231542D1 (de)	2009-04-23
US20050054638A1 (en)	2005-03-10
US20090131463A1 (en)	2009-05-21
CN1289486C (zh)	2006-12-13
PT1456182E (pt)	2009-05-26
US20120095011A1 (en)	2012-04-19
IS7294A (is)	2004-06-03
EG24930A (en)	2011-01-11
SE0104140D0 (sv)	2001-12-07
HK1067631A1 (en)	2005-04-15
NO327502B1 (no)	2009-07-27
TWI324152B (en)	2010-05-01
AU2002365864A1 (en)	2003-06-17
ATE425150T1 (de)	2009-03-15
AR037736A1 (es)	2004-12-01
NO20042872L (no)	2004-07-06
HUP0401855A2 (hu)	2004-12-28
MXPA04005347A (es)	2004-09-27
TW200409634A (en)	2004-06-16
CA2467838C (fr)	2010-10-12
EP1456182A1 (fr)	2004-09-15
JP4347051B2 (ja)	2009-10-21
SI1456182T1 (sl)	2009-08-31
CA2467838A1 (fr)	2003-06-12
AU2002365864B2 (en)	2007-08-30
PL369528A1 (en)	2005-05-02
BR0214605A (pt)	2004-09-14
MY135705A (en)	2008-06-30
RU2004121029A (ru)	2006-01-10
IL162376A0 (en)	2005-11-20
KR100930558B1 (ko)	2009-12-09
US7521453B2 (en)	2009-04-21
WO2003048133A1 (fr)	2003-06-12
JP2005515998A (ja)	2005-06-02
RU2317291C2 (ru)	2008-02-20
CN1617858A (zh)	2005-05-18
KR20050044698A (ko)	2005-05-12
DK1456182T3 (da)	2009-06-29
ES2323125T3 (es)	2009-07-07
NZ533130A (en)	2006-11-30
CY1109101T1 (el)	2014-07-02

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