NO322297B1 - Substituerte bisycliske derivater, anvendelse derav samt farmasoytisk sammensetning. - Google Patents
Substituerte bisycliske derivater, anvendelse derav samt farmasoytisk sammensetning. Download PDFInfo
- Publication number
- NO322297B1 NO322297B1 NO20013671A NO20013671A NO322297B1 NO 322297 B1 NO322297 B1 NO 322297B1 NO 20013671 A NO20013671 A NO 20013671A NO 20013671 A NO20013671 A NO 20013671A NO 322297 B1 NO322297 B1 NO 322297B1
- Authority
- NO
- Norway
- Prior art keywords
- cancer
- phenoxy
- methyl
- optionally substituted
- alkyl
- Prior art date
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- KTDGOUSDBBFBRO-UHFFFAOYSA-N tert-butyl 3-ethynylpyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(C#C)C1 KTDGOUSDBBFBRO-UHFFFAOYSA-N 0.000 description 1
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- OAXARSVKYJPDPA-UHFFFAOYSA-N tert-butyl 4-prop-2-ynylpiperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCN(CC#C)CC1 OAXARSVKYJPDPA-UHFFFAOYSA-N 0.000 description 1
- SBWYTQQSTIUXOP-UHFFFAOYSA-N tert-butyl n-(1-hydroxy-2-methylpropan-2-yl)carbamate Chemical compound CC(C)(C)OC(=O)NC(C)(C)CO SBWYTQQSTIUXOP-UHFFFAOYSA-N 0.000 description 1
- ACNRTYKOPZDRCO-UHFFFAOYSA-N tert-butyl n-(2-oxoethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCC=O ACNRTYKOPZDRCO-UHFFFAOYSA-N 0.000 description 1
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- IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 1
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- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical class CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
- C07D239/94—Nitrogen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
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- 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
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—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 chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D403/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D403/06—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 carbon chain containing only aliphatic carbon 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
- 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
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
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Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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US11734699P | 1999-01-27 | 1999-01-27 | |
PCT/IB1999/001934 WO2000044728A1 (en) | 1999-01-27 | 1999-12-06 | Substituted bicyclic derivatives useful as anticancer agents |
Publications (3)
Publication Number | Publication Date |
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NO20013671D0 NO20013671D0 (no) | 2001-07-26 |
NO20013671L NO20013671L (no) | 2001-09-26 |
NO322297B1 true NO322297B1 (no) | 2006-09-11 |
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NO20013671A NO322297B1 (no) | 1999-01-27 | 2001-07-26 | Substituerte bisycliske derivater, anvendelse derav samt farmasoytisk sammensetning. |
Country Status (45)
Families Citing this family (173)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DK1119567T3 (da) | 1998-10-08 | 2005-07-25 | Astrazeneca Ab | Quinazolinderivater |
UA71945C2 (en) * | 1999-01-27 | 2005-01-17 | Pfizer Prod Inc | Substituted bicyclic derivatives being used as anticancer agents |
AU763618B2 (en) | 1999-02-10 | 2003-07-31 | Astrazeneca Ab | Quinazoline derivatives as angiogenesis inhibitors |
MXPA02002938A (es) * | 1999-09-17 | 2004-12-06 | Abbott Gmbh & Co Kg | Inhibidores de cinasa como agentes agentes terapeuticos. |
US7071199B1 (en) | 1999-09-17 | 2006-07-04 | Abbott Gmbh & Cco. Kg | Kinase inhibitors as therapeutic agents |
DE60108754T2 (de) * | 2000-06-22 | 2005-06-23 | Pfizer Products Inc., Groton | Substituierte bizyklische derivate für die behandlung von unnormalem zellwachstum |
CA2415469A1 (en) | 2000-08-09 | 2002-02-14 | Astrazeneca Ab | Quinoline derivatives having vegf inhibiting activity |
KR100600550B1 (ko) | 2000-10-20 | 2006-07-13 | 에자이 가부시키가이샤 | 질소 함유 방향환 유도체 |
UY27225A1 (es) * | 2001-03-23 | 2002-10-31 | Bayer Corp | Inhibidores de la rho-quinasa |
CA2441492C (en) * | 2001-03-23 | 2011-08-09 | Bayer Corporation | Rho-kinase inhibitors |
ATE330956T1 (de) * | 2001-04-13 | 2006-07-15 | Pfizer Prod Inc | Bizyklisch substituierte 4- aminopyridopyrimidinderivate |
AU2002345792A1 (en) | 2001-06-21 | 2003-01-08 | Pfizer Inc. | Thienopyridine and thienopyrimidine anticancer agents |
GB0126433D0 (en) * | 2001-11-03 | 2002-01-02 | Astrazeneca Ab | Compounds |
US20050043336A1 (en) * | 2001-11-03 | 2005-02-24 | Hennequin Laurent Francois Andre | Quinazoline derivatives as antitumor agents |
DE60223279T2 (de) * | 2001-11-30 | 2008-05-29 | Osi Pharmaceuticals, Inc. | Verfahren für die herstellung substituierter bicyclischer derivate zur behandlung von anomalem zellwachstum |
EP1465632A1 (en) * | 2001-12-12 | 2004-10-13 | Pfizer Products Inc. | Quinazoline derivatives for the treatment of abnormal cell growth |
EP1463507A1 (en) * | 2001-12-19 | 2004-10-06 | SmithKline Beecham Corporation | Thienopyrimidine compounds as protein tyrosine kinase inhibitors |
US20030143165A1 (en) * | 2002-01-25 | 2003-07-31 | Allan Evans | NSAID-containing topical formulations that demonstrate chemopreventive activity |
RU2365588C2 (ru) | 2002-02-01 | 2009-08-27 | Астразенека Аб | Хиназолиновые соединения |
TW200302722A (en) * | 2002-02-13 | 2003-08-16 | Astrazeneca Ab | Therapeutic agents |
US6924285B2 (en) | 2002-03-30 | 2005-08-02 | Boehringer Ingelheim Pharma Gmbh & Co. | Bicyclic heterocyclic compounds, pharmaceutical compositions containing these compounds, their use and process for preparing them |
NZ535641A (en) * | 2002-05-07 | 2006-10-27 | Neurosearch As | Novel azacyclic ethynyl derivatives |
NZ536308A (en) * | 2002-05-24 | 2009-01-31 | Angiotech Int Ag | Compositions and methods for coating medical implants |
US8313760B2 (en) * | 2002-05-24 | 2012-11-20 | Angiotech International Ag | Compositions and methods for coating medical implants |
ATE323702T1 (de) | 2002-08-06 | 2006-05-15 | Astrazeneca Ab | Kondensierte pyridine und pyrimidine mit tie2 (tek) aktivität |
NZ540092A (en) | 2002-11-20 | 2007-06-29 | Array Biopharma Inc | Cyanoguanidines and cyanoamidines as ErbB2 and EGFR inhibitors |
US20040186160A1 (en) * | 2002-12-13 | 2004-09-23 | Sugen, Inc. | Hexahydro-cyclohepta-pyrrole oxindole as potent kinase inhibitors |
PL377686A1 (pl) * | 2002-12-18 | 2006-02-06 | Pfizer Products Inc. | Pochodne 4-anilinochinazoliny do leczenia anormalnego wzrostu komórek |
OA12977A (en) * | 2002-12-19 | 2006-10-13 | Pfizer | 2-(1H-indazol-6-ylamino)-benzamide compounds as protein kinases inhibitors useful for the treatment of ophthamic diseases. |
GB0309009D0 (en) * | 2003-04-22 | 2003-05-28 | Astrazeneca Ab | Quinazoline derivatives |
GB0309850D0 (en) | 2003-04-30 | 2003-06-04 | Astrazeneca Ab | Quinazoline derivatives |
WO2004106308A1 (en) * | 2003-05-27 | 2004-12-09 | Pfizer Products Inc. | Quinazolines and pyrido [3,4-d] pyrimidines as receptor tyrosine kinase inhibitors |
US8309562B2 (en) | 2003-07-03 | 2012-11-13 | Myrexis, Inc. | Compounds and therapeutical use thereof |
US7618975B2 (en) * | 2003-07-03 | 2009-11-17 | Myriad Pharmaceuticals, Inc. | 4-arylamino-quinazolines and analogs as activators of caspases and inducers of apoptosis and the use thereof |
HN2004000285A (es) * | 2003-08-04 | 2006-04-27 | Pfizer Prod Inc | ANTICUERPOS DIRIGIDOS A c-MET |
AR045563A1 (es) | 2003-09-10 | 2005-11-02 | Warner Lambert Co | Anticuerpos dirigidos a m-csf |
US20070032508A1 (en) * | 2003-09-16 | 2007-02-08 | Bradbury Robert H | Quinazoline derivatives as tyrosine kinase inhibitors |
GB0322409D0 (en) | 2003-09-25 | 2003-10-29 | Astrazeneca Ab | Quinazoline derivatives |
CN101337930B (zh) | 2003-11-11 | 2010-09-08 | 卫材R&D管理有限公司 | 脲衍生物的制备方法 |
GB0326459D0 (en) | 2003-11-13 | 2003-12-17 | Astrazeneca Ab | Quinazoline derivatives |
AU2004293463A1 (en) * | 2003-11-20 | 2005-06-09 | Angiotech International Ag | Implantable sensors and implantable pumps and anti-scarring agents |
GB0330002D0 (en) | 2003-12-24 | 2004-01-28 | Astrazeneca Ab | Quinazoline derivatives |
WO2005075439A1 (en) | 2004-02-03 | 2005-08-18 | Astrazeneca Ab | Quinazoline derivatives |
WO2005094830A1 (en) * | 2004-03-30 | 2005-10-13 | Pfizer Products Inc. | Combinations of signal transduction inhibitors |
EP1731523A4 (en) * | 2004-04-01 | 2009-08-12 | Takeda Pharmaceutical | THIAZOLOPYRIMIDINE DERIVATIVE |
CA2569016C (en) * | 2004-06-02 | 2012-11-27 | Takeda Pharmaceutical Company Limited | Fused heterocyclic compound |
MXPA06014125A (es) * | 2004-06-04 | 2007-01-31 | Astrazeneca Ab | Derivados de quinazolina en la forma de cinasas de tirosina de receptor erbb. |
US7601725B2 (en) * | 2004-07-16 | 2009-10-13 | Sunesis Pharmaceuticals, Inc. | Thienopyrimidines useful as Aurora kinase inhibitors |
EP1797054A2 (en) * | 2004-08-02 | 2007-06-20 | OSI Pharmaceuticals, Inc. | Aryl-amino substituted pyrrolopyrimidine multi-kinase inhibiting compounds |
JP2008510792A (ja) * | 2004-08-26 | 2008-04-10 | ファイザー・インク | タンパク質チロシンキナーゼ阻害剤としてのアミノヘテロアリール化合物 |
ES2355923T3 (es) * | 2004-08-26 | 2011-04-01 | Pfizer, Inc. | Compuestos de aminoheteroarilo sustituidos con pirazol como inhibidores de proteina quinasa. |
ES2341351T3 (es) | 2004-08-26 | 2010-06-18 | Pfizer, Inc. | Compuestos de aminoheteroarilo enantiomericamente puros como inhibidores de proteina cinasas. |
ATE428421T1 (de) | 2004-09-17 | 2009-05-15 | Eisai R&D Man Co Ltd | Medizinische zusammensetzung mit verbesserter stabilität und reduzierten gelierungseigenschaften |
US7285569B2 (en) | 2004-09-24 | 2007-10-23 | Hoff Hoffmann-La Roche Inc. | Tricycles, their manufacture and use as pharmaceutical agents |
TW200624431A (en) | 2004-09-24 | 2006-07-16 | Hoffmann La Roche | Phthalazinone derivatives, their manufacture and use as pharmaceutical agents |
US20060107555A1 (en) * | 2004-11-09 | 2006-05-25 | Curtis Marc D | Universal snow plow adapter |
ATE501148T1 (de) | 2004-12-14 | 2011-03-15 | Astrazeneca Ab | Pyrazolopyrimidinverbindungen als antitumormittel |
JP2008526776A (ja) * | 2005-01-03 | 2008-07-24 | ミリアド ジェネティクス, インコーポレイテッド | 脳癌の治療の方法 |
CA2592900A1 (en) | 2005-01-03 | 2006-07-13 | Myriad Genetics Inc. | Nitrogen containing bicyclic compounds and therapeutical use thereof |
US8258145B2 (en) | 2005-01-03 | 2012-09-04 | Myrexis, Inc. | Method of treating brain cancer |
GB0504474D0 (en) * | 2005-03-04 | 2005-04-13 | Astrazeneca Ab | Chemical compounds |
KR20080003390A (ko) | 2005-03-31 | 2008-01-07 | 어젠시스 인코포레이티드 | 161p2f10b 단백질과 결합하는 항체 및 관련 분자 |
BRPI0608178A2 (pt) | 2005-04-14 | 2009-11-17 | Hoffmann La Roche | derivados de aminopirazol, sua fabricação, composição farmacêutica e uso como agentes farmacêuticos |
GEP20115226B (en) | 2005-04-26 | 2011-06-10 | Pfizer | P-cadherin antibodies |
GB0508715D0 (en) * | 2005-04-29 | 2005-06-08 | Astrazeneca Ab | Chemical compounds |
GB0508717D0 (en) * | 2005-04-29 | 2005-06-08 | Astrazeneca Ab | Chemical compounds |
EP1888523B1 (en) | 2005-06-03 | 2011-10-26 | Abbott Laboratories | Cyclobutyl amine derivatives |
WO2007015578A1 (ja) | 2005-08-02 | 2007-02-08 | Eisai R & D Management Co., Ltd. | 血管新生阻害物質の効果を検定する方法 |
ES2546069T3 (es) * | 2005-09-07 | 2015-09-18 | Amgen Fremont Inc. | Anticuerpos monoclonales humanos para quinasa-1 de tipo receptor de activina (ALK-1) |
EP1926996B1 (en) | 2005-09-20 | 2011-11-09 | OSI Pharmaceuticals, Inc. | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors |
WO2007034143A1 (en) * | 2005-09-20 | 2007-03-29 | Astrazeneca Ab | Quinazoline derivatives as anticancer agents |
WO2007034144A1 (en) * | 2005-09-20 | 2007-03-29 | Astrazeneca Ab | 4- (ih-indazol-s-yl-amino)-quinazoline compounds as erbb receptor tyrosine kinase inhibitors for the treatment of cancer |
US7576110B2 (en) | 2005-09-22 | 2009-08-18 | Abbott Laboratories | Benzothiazole cyclobutyl amine derivatives |
EP1960371B1 (en) * | 2005-12-02 | 2009-09-16 | AstraZeneca AB | Quinazoleine derivatives used as inhibitors of erbb tyrosine kinase |
JP2009517450A (ja) * | 2005-12-02 | 2009-04-30 | アストラゼネカ アクチボラグ | チロシンキナーゼ阻害薬としての4−アニリノ置換キナゾリン誘導体 |
TW200730527A (en) * | 2005-12-02 | 2007-08-16 | Takeda Pharmaceuticals Co | Fused heterocyclic compound |
JP2009531274A (ja) * | 2005-12-07 | 2009-09-03 | オーエスアイ・ファーマスーティカルズ・インコーポレーテッド | キナーゼ阻害性ピロロピリジン化合物 |
US7572809B2 (en) | 2005-12-19 | 2009-08-11 | Hoffmann-La Roche Inc. | Isoquinoline aminopyrazole derivatives |
AU2006330924B2 (en) | 2005-12-21 | 2012-03-15 | Abbvie Inc. | Anti-viral compounds |
ES2395386T3 (es) | 2005-12-21 | 2013-02-12 | Abbott Laboratories | Compuestos antivirales |
DE602006015861D1 (de) | 2005-12-21 | 2010-09-09 | Abbott Lab | Antivirale verbindungen |
US20070231298A1 (en) * | 2006-03-31 | 2007-10-04 | Cell Genesys, Inc. | Cytokine-expressing cancer immunotherapy combinations |
CN101490046A (zh) | 2006-05-09 | 2009-07-22 | 辉瑞产品公司 | 环烷基氨基酸衍生物及其药物组合物 |
CN101443009A (zh) | 2006-05-18 | 2009-05-27 | 卫材R&D管理有限公司 | 针对甲状腺癌的抗肿瘤剂 |
US9108948B2 (en) | 2006-06-23 | 2015-08-18 | Abbvie Inc. | Cyclopropyl amine derivatives |
EP2049472B1 (en) | 2006-06-23 | 2015-01-21 | AbbVie Bahamas Ltd. | Cyclopropyl amine derivatives as histamin h3 receptor modulators |
KR101472600B1 (ko) | 2006-08-28 | 2014-12-15 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 미분화형 위암에 대한 항종양제 |
EP1921070A1 (de) | 2006-11-10 | 2008-05-14 | Boehringer Ingelheim Pharma GmbH & Co. KG | Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstelllung |
EP2103620A1 (en) | 2006-12-12 | 2009-09-23 | Takeda Pharmaceutical Company Limited | Fused heterocyclic compound |
TWI399380B (zh) | 2006-12-20 | 2013-06-21 | Abbott Lab | 抗病毒化合物 |
WO2008093855A1 (ja) | 2007-01-29 | 2008-08-07 | Eisai R & D Management Co., Ltd. | 未分化型胃癌治療用組成物 |
KR100799821B1 (ko) * | 2007-02-05 | 2008-01-31 | 동화약품공업주식회사 | 신규한 이마티닙 캠실레이트 및 그의 제조방법 |
KR20090116782A (ko) | 2007-02-06 | 2009-11-11 | 베링거 인겔하임 인터내셔날 게엠베하 | 바이사이클릭 헤테로사이클, 당해 화합물을 함유하는 약물, 이의 용도 및 이의 제조방법 |
US8715665B2 (en) | 2007-04-13 | 2014-05-06 | The General Hospital Corporation | Methods for treating cancer resistant to ErbB therapeutics |
CA2683804A1 (en) * | 2007-04-13 | 2008-10-23 | Dana Farber Cancer Institute, Inc. | Receptor tyrosine kinase profiling |
US7956190B2 (en) | 2007-06-25 | 2011-06-07 | Hoffmann-La Roche Inc. | Benzimidazole amido derivatives as kinase inhibitors |
JP5518711B2 (ja) | 2007-09-07 | 2014-06-11 | アジェンシス,インコーポレイテッド | 24p4c12タンパク質に結合する抗体および関連分子 |
CA2704000C (en) | 2007-11-09 | 2016-12-13 | Eisai R&D Management Co., Ltd. | Combination of anti-angiogenic substance and anti-tumor platinum complex |
KR20100111291A (ko) | 2008-02-07 | 2010-10-14 | 베링거 인겔하임 인터내셔날 게엠베하 | 스피로사이클릭 헤테로사이클, 상기 화합물을 함유하는 약제, 이의 용도 및 이의 제조 방법 |
US20090233937A1 (en) * | 2008-03-12 | 2009-09-17 | Takeda Pharmaceutical Company Limited | Fused heterocyclic compound |
US7932036B1 (en) | 2008-03-12 | 2011-04-26 | Veridex, Llc | Methods of determining acute myeloid leukemia response to treatment with farnesyltransferase |
US8088782B2 (en) | 2008-05-13 | 2012-01-03 | Astrazeneca Ab | Crystalline 4-(3-chloro-2-fluoroanilino)-7 methoxy-6-{[1-(N-methylcarbamoylmethyl)piperidin-4-yl]oxy}quinazoline difumarate form A |
EP2315751A1 (en) * | 2008-06-26 | 2011-05-04 | Amgen Inc. | Alkynyl alcohols as kinase inhibitors |
WO2010011349A2 (en) * | 2008-07-25 | 2010-01-28 | Supergen, Inc. | Pyrimidine-2,4-diamine jak2 kinase inhibiting anti-inflammation use |
US8648191B2 (en) | 2008-08-08 | 2014-02-11 | Boehringer Ingelheim International Gmbh | Cyclohexyloxy substituted heterocycles, pharmaceutical compositions containing these compounds and processes for preparing them |
AR073501A1 (es) | 2008-09-08 | 2010-11-10 | Boehringer Ingelheim Int | Derivados de pirimido[5,4-d]pirimidina inhibidores de la tirosinoquinasa |
EP2241565A1 (en) | 2009-01-15 | 2010-10-20 | Universität Leipzig | Aurora kinase inhibitors compounds |
TW201041892A (en) * | 2009-02-09 | 2010-12-01 | Supergen Inc | Pyrrolopyrimidinyl Axl kinase inhibitors |
US20120189641A1 (en) | 2009-02-25 | 2012-07-26 | OSI Pharmaceuticals, LLC | Combination anti-cancer therapy |
US20110171124A1 (en) | 2009-02-26 | 2011-07-14 | Osi Pharmaceuticals, Inc. | In situ methods for monitoring the EMT status of tumor cells in vivo |
US8642834B2 (en) | 2009-02-27 | 2014-02-04 | OSI Pharmaceuticals, LLC | Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation |
WO2010098866A1 (en) | 2009-02-27 | 2010-09-02 | Supergen, Inc. | Cyclopentathiophene/cyclohexathiophene dna methyltransferase inhibitors |
JP2012519282A (ja) | 2009-02-27 | 2012-08-23 | オーエスアイ・ファーマシューティカルズ,エルエルシー | 間葉様腫瘍細胞またはその生成を阻害する薬剤を同定するための方法 |
WO2010099138A2 (en) | 2009-02-27 | 2010-09-02 | Osi Pharmaceuticals, Inc. | Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation |
US9186353B2 (en) | 2009-04-27 | 2015-11-17 | Abbvie Inc. | Treatment of osteoarthritis pain |
US20120157471A1 (en) | 2009-09-01 | 2012-06-21 | Pfizer Inc. | Benzimidazole derivatives |
CA2783656A1 (en) | 2010-03-03 | 2011-09-09 | OSI Pharmaceuticals, LLC | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors |
EP2542893A2 (en) | 2010-03-03 | 2013-01-09 | OSI Pharmaceuticals, LLC | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors |
KR101677790B1 (ko) | 2010-06-25 | 2016-11-18 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 키나제 저해 작용을 갖는 화합물의 병용에 의한 항종양제 |
CA2806112C (en) | 2010-07-28 | 2023-03-21 | Veridex, Llc | Methods of determining acute myeloid leukemia response to treatment with farnesyltransferase inhibitors |
US8853390B2 (en) | 2010-09-16 | 2014-10-07 | Abbvie Inc. | Processes for preparing 1,2-substituted cyclopropyl derivatives |
WO2012052948A1 (en) | 2010-10-20 | 2012-04-26 | Pfizer Inc. | Pyridine- 2- derivatives as smoothened receptor modulators |
KR20140016245A (ko) * | 2010-11-09 | 2014-02-07 | 후지안 하이시 파머수티클스, 인코포레이티드 | 키나아제 활성을 증진시키기 위한 화합물 및 이의 응용 |
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 |
RU2580609C2 (ru) | 2011-04-18 | 2016-04-10 | Эйсай Ар Энд Ди Менеджмент Ко., Лтд. | Противоопухолевое терапевтическое средство |
TR201905909T4 (tr) | 2011-04-19 | 2019-05-21 | Pfizer | Kanser tedavisi için anti-4-1bb antikorlarının ve adcc indükleyici antikorların kombinasyonları. |
US9896730B2 (en) | 2011-04-25 | 2018-02-20 | OSI Pharmaceuticals, LLC | Use of EMT gene signatures in cancer drug discovery, diagnostics, and treatment |
EP3444363B1 (en) | 2011-06-03 | 2020-11-25 | Eisai R&D Management Co., Ltd. | Biomarkers for prediciting and assessing responsiveness of thyroid and kidney cancer subjects to lenvatinib compounds |
DK2734205T3 (en) | 2011-07-21 | 2018-06-14 | Tolero Pharmaceuticals Inc | Heterocyclic Protein Kinase Inhibitors |
UA110259C2 (uk) | 2011-09-22 | 2015-12-10 | Пфайзер Інк. | Похідні піролопіримідину і пурину |
AU2012335247A1 (en) | 2011-11-08 | 2014-05-29 | Pfizer Inc. | Methods of treating inflammatory disorders using anti-M-CSF antibodies |
TWI577671B (zh) * | 2011-11-14 | 2017-04-11 | Sunshine Lake Pharma Co Ltd | Aminoquinazoline derivatives and salts thereof and methods of use thereof |
WO2013152252A1 (en) | 2012-04-06 | 2013-10-10 | OSI Pharmaceuticals, LLC | Combination anti-cancer therapy |
EP2909181B1 (en) | 2012-10-16 | 2017-08-09 | Tolero Pharmaceuticals, Inc. | Pkm2 modulators and methods for their use |
US9260426B2 (en) | 2012-12-14 | 2016-02-16 | Arrien Pharmaceuticals Llc | Substituted 1H-pyrrolo [2, 3-b] pyridine and 1H-pyrazolo [3, 4-b] pyridine derivatives as salt inducible kinase 2 (SIK2) inhibitors |
KR20150098605A (ko) | 2012-12-21 | 2015-08-28 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 퀴놀린 유도체의 비정질 형태 및 그의 제조방법 |
US9468681B2 (en) | 2013-03-01 | 2016-10-18 | California Institute Of Technology | Targeted nanoparticles |
JP6433974B2 (ja) | 2013-03-14 | 2018-12-05 | トレロ ファーマシューティカルズ, インコーポレイテッド | Jak2およびalk2阻害剤およびその使用方法 |
US9206188B2 (en) | 2013-04-18 | 2015-12-08 | Arrien Pharmaceuticals Llc | Substituted pyrrolo[2,3-b]pyridines as ITK and JAK inhibitors |
SG11201509278XA (en) | 2013-05-14 | 2015-12-30 | Eisai R&D Man Co Ltd | Biomarkers for predicting and assessing responsiveness of endometrial cancer subjects to lenvatinib compounds |
UA115388C2 (uk) | 2013-11-21 | 2017-10-25 | Пфайзер Інк. | 2,6-заміщені пуринові похідні та їх застосування в лікуванні проліферативних захворювань |
CN103784412A (zh) * | 2014-01-15 | 2014-05-14 | 青岛市肿瘤医院 | 一种盐酸埃克替尼分散片及其制备方法 |
WO2015155624A1 (en) | 2014-04-10 | 2015-10-15 | Pfizer Inc. | Dihydropyrrolopyrimidine derivatives |
CR20160497A (es) | 2014-04-30 | 2016-12-20 | Pfizer | Derivados de diheterociclo enlazado a cicloalquilo |
WO2016001789A1 (en) | 2014-06-30 | 2016-01-07 | Pfizer Inc. | Pyrimidine derivatives as pi3k inhibitors for use in the treatment of cancer |
SI3524595T1 (sl) | 2014-08-28 | 2022-10-28 | Eisai R&D Management Co., Ltd. | Derivat kinolina visoke čistosti in postopek njegove proizvodnje |
WO2016136745A1 (ja) | 2015-02-25 | 2016-09-01 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | キノリン誘導体の苦味抑制方法 |
KR102662228B1 (ko) | 2015-03-04 | 2024-05-02 | 머크 샤프 앤드 돔 코포레이션 | 암을 치료하기 위한 pd-1 길항제 및 vegfr/fgfr/ret 티로신 키나제 억제제의 조합 |
CN107995863A (zh) | 2015-04-20 | 2018-05-04 | 特雷罗药物股份有限公司 | 通过线粒体分析预测对阿伏西地的应答 |
AU2016264212B2 (en) | 2015-05-18 | 2020-10-22 | Sumitomo Pharma Oncology, Inc. | Alvocidib prodrugs having increased bioavailability |
CA2988707C (en) | 2015-06-16 | 2023-10-10 | Eisai R&D Management Co., Ltd. | Combination of cbp/catenin inhibitor and immune checkpoint inhibitor for treating cancer |
EP3317323B1 (en) | 2015-07-01 | 2021-05-26 | California Institute of Technology | Cationic mucic acid polymer-based delivery systems |
WO2017009751A1 (en) | 2015-07-15 | 2017-01-19 | Pfizer Inc. | Pyrimidine derivatives |
WO2017024073A1 (en) | 2015-08-03 | 2017-02-09 | Tolero Pharmaceuticals, Inc. | Combination therapies for treatment of cancer |
AU2016364855B2 (en) | 2015-12-03 | 2019-08-29 | Les Laboratoires Servier | MAT2A inhibitors for treating MTAP null cancer |
WO2018094275A1 (en) | 2016-11-18 | 2018-05-24 | Tolero Pharmaceuticals, Inc. | Alvocidib prodrugs and their use as protein kinase inhibitors |
WO2018119000A1 (en) | 2016-12-19 | 2018-06-28 | Tolero Pharmaceuticals, Inc. | Profiling peptides and methods for sensitivity profiling |
WO2019055579A1 (en) | 2017-09-12 | 2019-03-21 | Tolero Pharmaceuticals, Inc. | TREATMENT REGIME FOR CANCERS THAT ARE INSENSITIVE TO BCL-2 INHIBITORS USING THE MCL-1 ALVOCIDIB INHIBITOR |
EP3682881A4 (en) | 2017-09-14 | 2021-08-11 | Daiichi Sankyo Company, Limited | CONNECTION WITH CYCLICAL STRUCTURE |
US20200237766A1 (en) | 2017-10-13 | 2020-07-30 | Tolero Pharmaceuticals, Inc. | Pkm2 activators in combination with reactive oxygen species for treatment of cancer |
KR20190043437A (ko) | 2017-10-18 | 2019-04-26 | 씨제이헬스케어 주식회사 | 단백질 키나제 억제제로서의 헤테로고리 화합물 |
JP2021506974A (ja) * | 2017-12-18 | 2021-02-22 | スターングリーン、インク. | チロシンキナーゼ阻害剤として有用なピリミジン化合物 |
CA3099440A1 (en) | 2018-06-13 | 2019-12-19 | California Institute Of Technology | Nanoparticles for crossing the blood brain barrier and methods of treatment using the same |
JP2021530554A (ja) | 2018-07-26 | 2021-11-11 | スミトモ ダイニッポン ファーマ オンコロジー, インコーポレイテッド | 異常なacvr1発現を伴う疾患を処置するための方法およびそこで使用するためのacvr1阻害剤 |
SG11202102981SA (en) | 2018-09-25 | 2021-04-29 | Black Diamond Therapeutics Inc | Quinazoline derivatives as tyrosine kinase inhibitor, compositions, methods of making them and their use |
EP3890749A4 (en) | 2018-12-04 | 2022-08-03 | Sumitomo Dainippon Pharma Oncology, Inc. | CDK9 INHIBITORS AND POLYMORPHS THEREOF FOR USE AS CANCER TREATMENT AGENT |
WO2020167990A1 (en) | 2019-02-12 | 2020-08-20 | Tolero Pharmaceuticals, Inc. | Formulations comprising heterocyclic protein kinase inhibitors |
WO2020191326A1 (en) | 2019-03-20 | 2020-09-24 | Sumitomo Dainippon Pharma Oncology, Inc. | Treatment of acute myeloid leukemia (aml) with venetoclax failure |
CA3133460A1 (en) | 2019-03-22 | 2020-10-01 | Sumitomo Dainippon Pharma Oncology, Inc. | Compositions comprising pkm2 modulators and methods of treatment using the same |
WO2021155006A1 (en) | 2020-01-31 | 2021-08-05 | Les Laboratoires Servier Sas | Inhibitors of cyclin-dependent kinases and uses thereof |
CA3175102A1 (en) * | 2020-03-13 | 2021-09-16 | Suzhou Zanrong Pharma Ltd. | Erbb receptor inhibitors as anti-tumor agents |
KR102234530B1 (ko) * | 2020-09-01 | 2021-03-31 | 대한민국 | 신규 톨트라주릴 유도체 및 이를 포함하는 쿠도아충 예방·치료를 위한 약학 조성물 |
PE20240327A1 (es) | 2021-04-13 | 2024-02-22 | Nuvalent Inc | Heterociclos con sustitucion amino para tratar canceres con mutaciones de egfr |
Family Cites Families (42)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH0222274A (ja) * | 1988-01-23 | 1990-01-25 | Kyowa Hakko Kogyo Co Ltd | ピリダジノン誘導体 |
US5034393A (en) | 1989-07-27 | 1991-07-23 | Dowelanco | Fungicidal use of pyridopyrimidine, pteridine, pyrimidopyrimidine, pyrimidopyridazine, and pyrimido-1,2,4-triazine derivatives |
US5409930A (en) | 1991-05-10 | 1995-04-25 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Bis mono- and bicyclic aryl and heteroaryl compounds which inhibit EGF and/or PDGF receptor tyrosine kinase |
US5710158A (en) | 1991-05-10 | 1998-01-20 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Aryl and heteroaryl quinazoline compounds which inhibit EGF and/or PDGF receptor tyrosine kinase |
NZ243082A (en) | 1991-06-28 | 1995-02-24 | Ici Plc | 4-anilino-quinazoline derivatives; pharmaceutical compositions, preparatory processes, and use thereof |
DK0612321T3 (da) * | 1991-10-09 | 1999-12-13 | Syntex Inc | Pyridopyridazinon- og pyridazinthionforbindelser med PDE IV inhiberende aktivitet |
US5283242A (en) | 1991-10-24 | 1994-02-01 | American Home Products Corporation | Substituted benzimidazoles and quinazolines as antihypertensives |
US5256781A (en) | 1991-10-24 | 1993-10-26 | American Home Products Corporation | Substituted quinazolines as angiotensin II antagonists |
GB9300059D0 (en) | 1992-01-20 | 1993-03-03 | Zeneca Ltd | Quinazoline derivatives |
DK40192D0 (da) | 1992-03-26 | 1992-03-26 | Neurosearch As | Imidazolforbindelser, deres fremstilling og anvendelse |
JP2994165B2 (ja) * | 1992-06-26 | 1999-12-27 | ゼネカ・リミテッド | キナゾリン誘導体、その製造法および該キナゾリン誘導体を含有する抗癌作用を得るための医薬調剤 |
GB9323290D0 (en) * | 1992-12-10 | 1994-01-05 | Zeneca Ltd | Quinazoline derivatives |
GB9314884D0 (en) | 1993-07-19 | 1993-09-01 | Zeneca Ltd | Tricyclic derivatives |
GB9314893D0 (en) * | 1993-07-19 | 1993-09-01 | Zeneca Ltd | Quinazoline derivatives |
IL112249A (en) | 1994-01-25 | 2001-11-25 | Warner Lambert Co | Pharmaceutical compositions containing di and tricyclic pyrimidine derivatives for inhibiting tyrosine kinases of the epidermal growth factor receptor family and some new such compounds |
JP2890267B2 (ja) | 1994-02-23 | 1999-05-10 | ファイザー インク. | 4−ヘテロサイクリル−置換キナゾリン誘導体、その調製法および抗癌剤としてのその使用法 |
TW414798B (en) * | 1994-09-07 | 2000-12-11 | Thomae Gmbh Dr K | Pyrimido (5,4-d) pyrimidines, medicaments comprising these compounds, their use and processes for their preparation |
GB9510757D0 (en) * | 1994-09-19 | 1995-07-19 | Wellcome Found | Therapeuticaly active compounds |
GB9424233D0 (en) | 1994-11-30 | 1995-01-18 | Zeneca Ltd | Quinazoline derivatives |
KR100437580B1 (ko) * | 1995-03-14 | 2004-07-16 | 노파르티스 아게 | 삼치환된페닐유도체 |
EP1110953B1 (en) | 1995-03-30 | 2009-10-28 | Pfizer Products Inc. | Quinazoline derivatives |
US5747498A (en) | 1996-05-28 | 1998-05-05 | Pfizer Inc. | Alkynyl and azido-substituted 4-anilinoquinazolines |
MX9709867A (es) | 1995-06-07 | 1998-03-31 | Pfizer | Derivados de pirimidina condensados con un anillo heterociclico, composiciones que contienen los mismos, y uso de los mismos. |
DK0836605T3 (da) * | 1995-07-06 | 2002-05-13 | Novartis Ag | Pyrrolopyrimidiner og fremgangsmåder til deres fremstilling |
AR004010A1 (es) * | 1995-10-11 | 1998-09-30 | Glaxo Group Ltd | Compuestos heterociclicos |
DE69620445T2 (de) | 1995-12-08 | 2002-12-12 | Janssen Pharmaceutica N.V., Beerse | (imidazol-5-yl)methyl-2-chinolinoderivate als farnesyl protein transferase inhibitoren |
GB9624482D0 (en) | 1995-12-18 | 1997-01-15 | Zeneca Phaema S A | Chemical compounds |
GB9603095D0 (en) | 1996-02-14 | 1996-04-10 | Zeneca Ltd | Quinazoline derivatives |
GB9603097D0 (en) | 1996-02-14 | 1996-04-10 | Zeneca Ltd | Quinazoline compounds |
DE19629652A1 (de) * | 1996-03-06 | 1998-01-29 | Thomae Gmbh Dr K | 4-Amino-pyrimidin-Derivate, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung |
DE19608653A1 (de) * | 1996-03-06 | 1997-09-11 | Thomae Gmbh Dr K | Pyrimido[5,4-d]pyrimidine, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung |
BR9710362A (pt) * | 1996-07-13 | 1999-08-17 | Glaxo Group Ltd | Composto formula-ao farmaceutica utiliza-ao de um composto processos de tratamento de um ser humano ou animal sofrendo de uma mediada por atividade anormal de cinase de proteina tirosina e para a prepara-ao de um composto |
JP4386967B2 (ja) * | 1996-07-13 | 2009-12-16 | グラクソ、グループ、リミテッド | プロテインチロシンキナーゼ阻害剤としての縮合複素環式化合物 |
HRP970371A2 (en) * | 1996-07-13 | 1998-08-31 | Kathryn Jane Smith | Heterocyclic compounds |
ES2297864T3 (es) * | 1996-08-23 | 2008-05-01 | Novartis Ag | Pirrolopirimidinas sustituidas y procesos para su preparacion. |
NZ330571A (en) | 1996-10-01 | 1999-10-28 | Kyowa Hakko Kogyo Kk | Nitrogenous heterocyclic compounds that may contain sulphur or oxygen |
EP0837063A1 (en) * | 1996-10-17 | 1998-04-22 | Pfizer Inc. | 4-Aminoquinazoline derivatives |
WO1998023613A1 (en) * | 1996-11-27 | 1998-06-04 | Pfizer Inc. | Fused bicyclic pyrimidine derivatives |
DE19653646A1 (de) | 1996-12-20 | 1998-06-25 | Hoechst Ag | Substituierte Purinderivate, Verfahren zu deren Herstellung, sie enthaltende Mittel und deren Verwendung |
PL340589A1 (en) * | 1997-11-11 | 2001-02-12 | Pfizer Prod Inc | Derivatives of thienepyrimidine and thienepyridine useful as anticarcinogenic agents |
JP3270834B2 (ja) * | 1999-01-27 | 2002-04-02 | ファイザー・プロダクツ・インク | 抗がん剤として有用なヘテロ芳香族二環式誘導体 |
UA71945C2 (en) * | 1999-01-27 | 2005-01-17 | Pfizer Prod Inc | Substituted bicyclic derivatives being used as anticancer agents |
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